Materiały źródłowe

• #1 Uterine Leiomyomata – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK546680/

  Uterine leiomyomata, also known as uterine fibroids, are the most common benign gynecologic tumors, occurring in 50% to 70% of females by menopause, with rates reaching over 80% in Black women. […] Leiomyomata originate from uterine smooth muscle cells in the myometrium, and their growth is primarily stimulated by circulating estrogen. […] Several molecular studies have identified specific gene mutations associated with leiomyomata, the most common of which is the MED12 gene located on chromosome X at position q13. […] The MED12 gene codes for one of the key proteins in the mediator complex (subunit 12) that regulates RNA polymerase II; a mutation in this gene occurs in approximately 70% of uterine leiomyomas. […] Additionally, uterine leiomyomata are hormonally sensitive tumors, and evidence has demonstrated that leiomyomas overexpress certain estrogen and progesterone receptors when compared to normal surrounding myometrium.

• #2 Update on the Role and Regulatory Mechanism of Extracellular Matrix in the Pathogenesis of Uterine Fibroids

  https://www.mdpi.com/1422-0067/24/6/5778

  Uterine fibroids (UFs), also known as leiomyomas, are benign tumors of the myometrium affecting over 70% of women worldwide, particularly women of color. […] Although benign, UFs are associated with significant morbidity; they are the primary indication for hysterectomy and a major source of gynecologic and reproductive dysfunction, ranging from menorrhagia and pelvic pain to infertility, recurrent miscarriage, and preterm labor. […] So far, the molecular mechanisms underlying the pathogenesis of UFs are still quite limited. […] Excessive ECM accumulation and aberrant remodeling are crucial for fibrotic diseases and excessive ECM deposition is the central characteristics of UFs. […] This review summarizes the recent progress of ascertaining the biological functions and regulatory mechanisms in UFs, from the perspective of factors regulating ECM production, ECM-mediated signaling, and pharmacological drugs targeting ECM accumulation.

• #3 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  Uterine leiomyomas (fibroids or myomas) are benign tumors of uterus and clinically apparent in a large part of reproductive aged women. […] Despite the prevalence of this condition, myoma research is underfunded compared to other nonmalignant diseases. To date, several pathogenetic factors such as genetics, microRNA, steroids, growth factors, cytokines, chemokines, and extracellular matrix components have been implicated in the development and growth of leiomyoma. […] Nowadays, conflicting data about the pathogenesis of leiomyomas coexist in the literature. The development of uterine myomas can be linked to predisposing risk factors, initiators and genetic mechanisms, promoters, and effectors. […] Even if many risk factors suggested by epidemiologic studies have linked uterine leiomyomas to the effects of estrogens and progesterone levels and their metabolism, other mechanisms may be involved in fibroids pathogenesis.

• #4 Uterine fibroids (leiomyomas): Histology and pathogenesis – UpToDate

  https://www.uptodate.com/contents/uterine-fibroids-leiomyomas-histology-and-pathogenesis/print

  Uterine fibroids (leiomyomas) are the most common pelvic neoplasm in females. They are nonmalignant monoclonal tumors arising from the smooth muscle cells of the myometrium. The pathogenesis of leiomyomas is not well understood. Genetic predisposition, environmental factors, steroid hormones, and growth factors important in fibrotic processes and angiogenesis all play a role in the formation and growth of uterine fibroids. […] The disease is heterogeneous, and different fibroids within the same uterus may have different etiologies and arise from different somatic mutations. […] Leiomyoma-related effects on the function and structure of the endometrium are the final common pathways in the pathogenesis of excessive bleeding in myomatous uteri, and there is evidence of both histologic changes in the endometrium and endometrial vasculature in these uteri. […] The pathogenesis of uterine leiomyomas is reviewed here. At least two distinct components contribute to leiomyoma development.

• #5 Uterine Leiomyomata – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK546680/

  Studies indicate that the ovarian steroids estradiol and progesterone promote the growth of leiomyomas, and myometrial cells with high levels of estrogen and progesterone receptors can stimulate the growth of adjacent uterine leiomyomata stem cells in a paracrine fashion. […] Uterine fibroids are benign monoclonal tumors originating from smooth muscle cells within the uterus. […] The exact initiating factor of fibroid formation remains unclear. However, prevailing theories highlight the role of reproductive hormones, inherent abnormalities of the myometrium, and predisposing genetic variations that affect cell signaling pathways.

• #6 Uterine fibroids (leiomyomas): Histology and pathogenesis – UpToDate

  https://www.uptodate.com/contents/uterine-fibroids-leiomyomas-histology-and-pathogenesis/print

  Uterine fibroids (leiomyomas) are the most common pelvic neoplasm in females. They are nonmalignant monoclonal tumors arising from the smooth muscle cells of the myometrium. The pathogenesis of leiomyomas is not well understood. Genetic predisposition, environmental factors, steroid hormones, and growth factors important in fibrotic processes and angiogenesis all play a role in the formation and growth of uterine fibroids. […] The disease is heterogeneous, and different fibroids within the same uterus may have different etiologies and arise from different somatic mutations. […] Leiomyoma-related effects on the function and structure of the endometrium are the final common pathways in the pathogenesis of excessive bleeding in myomatous uteri, and there is evidence of both histologic changes in the endometrium and endometrial vasculature in these uteri. […] The pathogenesis of uterine leiomyomas is reviewed here. At least two distinct components contribute to leiomyoma development.

• #7 Progesterone Signaling and Uterine Fibroid Pathogenesis; Molecular Mechanisms and Potential Therapeutics

  https://www.mdpi.com/2073-4409/12/8/1117

  Uterine fibroids (UFs) are the most important benign neoplastic threat to women’s health worldwide, with a prevalence of up to 80% in premenopausal women, and can cause heavy menstrual bleeding, pain, and infertility. Progesterone signaling plays a crucial role in the development and growth of UFs. Progesterone promotes the proliferation of UF cells by activating several signaling pathways genetically and epigenetically. […] The UF pathogenesis model invokes the genetic transformation of a single myometrial stem cell (MMSC) into a tumor-initiating cell (UFSC) that seeds and sustains clonal tumor growth. This is characterized by an increase in cell size and number as well as abundant ECM production, under the influence of endocrine, autocrine, and paracrine growth factors and hormone receptor signaling.

• #8

  https://link.springer.com/article/10.1007/s43032-022-00960-9

  Uterine fibroids (UFs) (leiomyomas or myomas) are the most common clonal neoplasms of the uterus in women of reproductive age worldwide. […] UFs originate from myometrium consist of smooth muscle and fibroblast components, in addition to a substantial amount of fibrous extracellular matrix which all contribute to the pathogenetic process. […] The prevailing model for UF pathogenesis invokes the genetic transformation of a single myometrial stem cell (MMSC) into a tumor-initiating cell that seeds and sustains clonal tumor growth, characterized by an increase in cell size and number and abundant extracellular matrix production, under the influence of endocrine, autocrine, and paracrine growth factors and hormone receptor signaling. […] Most importantly, the fibroid stem cells acquire the mutations in the gene encoding Mediator complex subunit MED12 and are dominant drivers of UFs in women of diverse racial and ethnic origins.

• #9 Progesterone Signaling and Uterine Fibroid Pathogenesis; Molecular Mechanisms and Potential Therapeutics

  https://www.mdpi.com/2073-4409/12/8/1117

  Uterine fibroids (UFs) are the most important benign neoplastic threat to women’s health worldwide, with a prevalence of up to 80% in premenopausal women, and can cause heavy menstrual bleeding, pain, and infertility. Progesterone signaling plays a crucial role in the development and growth of UFs. Progesterone promotes the proliferation of UF cells by activating several signaling pathways genetically and epigenetically. […] The UF pathogenesis model invokes the genetic transformation of a single myometrial stem cell (MMSC) into a tumor-initiating cell (UFSC) that seeds and sustains clonal tumor growth. This is characterized by an increase in cell size and number as well as abundant ECM production, under the influence of endocrine, autocrine, and paracrine growth factors and hormone receptor signaling.

• #10 Uterine fibroids (leiomyomas): Histology and pathogenesis – UpToDate

  https://www.uptodate.com/contents/uterine-fibroids-leiomyomas-histology-and-pathogenesis

  Uterine fibroids (leiomyomas) are the most common pelvic neoplasm in females. They are nonmalignant monoclonal tumors arising from the smooth muscle cells of the myometrium. The pathogenesis of leiomyomas is not well understood. Genetic predisposition, environmental factors, steroid hormones, and growth factors important in fibrotic processes and angiogenesis all play a role in the formation and growth of uterine fibroids. […] Leiomyoma-related effects on the function and structure of the endometrium are the final common pathways in the pathogenesis of excessive bleeding in myomatous uteri, and there is evidence of both histologic changes in the endometrium and endometrial vasculature in these uteri. […] The pathogenesis of uterine leiomyomas is reviewed here. At least two distinct components contribute to leiomyoma development.

• #11 Uterine fibroid – Wikipedia

  https://en.wikipedia.org/wiki/Uterine_fibroid

  Expansion of uterine fibroids occurs by a slow rate of cell proliferation combined with the production of copious amounts of extracellular matrix. […] A small population of the cells in a uterine fibroid have properties of stem cells or progenitor cells, and contribute significantly to ovarian steroid-dependent growth of fibroids. These stem-progenitor cells are deficient in estrogen receptor and progesterone receptor and instead rely on substantially higher levels of these receptors in surrounding differentiated cells to mediate estrogen and progesterone actions via paracrine signaling.

• #12 Uterine fibroid – Wikipedia

  https://en.wikipedia.org/wiki/Uterine_fibroid

  Fibroids are monoclonal tumors and approximately 4050% show karyotypically detectable chromosomal abnormalities. When multiple fibroids are present they frequently have unrelated genetic defects. Specific mutations of the MED12 protein have been noted in 70 percent of fibroids. […] The exact cause of fibroids is not clearly understood, but the current working hypothesis is that genetic predispositions, prenatal hormone exposure and the effects of hormones, growth factors and xenoestrogens cause fibroid growth. Known risk factors are African descent, obesity, polycystic ovary syndrome, diabetes, hypertension, and never having given birth. […] It is believed that estrogen and progesterone have a mitogenic effect on leiomyoma cells and also act by influencing (directly and indirectly) a large number of growth factors, cytokines and apoptotic factors as well as other hormones. Furthermore, the actions of estrogen and progesterone are modulated by the cross-talk between estrogen, progesterone and prolactin signaling which controls the expression of the respective nuclear receptors. It is believed that estrogen promotes growth by up-regulating IGF-1, EGFR, TGF-beta1, TGF-beta3 and PDGF, and promotes aberrant survival of leiomyoma cells by down-regulating p53, increasing expression of the anti-apoptotic factor PCP4 and antagonizing PPAR-gamma signaling. Progesterone is thought to promote the growth of leiomyoma through up-regulating EGF, TGF-beta1 and TGF-beta3, and promotes survival through up-regulating Bcl-2 expression and down-regulating TNF-alpha. Progesterone is believed to counteract growth by downregulating IGF-1.

• #13 Uterine fibroid – Wikipedia

  https://en.wikipedia.org/wiki/Uterine_fibroid

  Fibroids are monoclonal tumors and approximately 4050% show karyotypically detectable chromosomal abnormalities. When multiple fibroids are present they frequently have unrelated genetic defects. Specific mutations of the MED12 protein have been noted in 70 percent of fibroids. […] The exact cause of fibroids is not clearly understood, but the current working hypothesis is that genetic predispositions, prenatal hormone exposure and the effects of hormones, growth factors and xenoestrogens cause fibroid growth. Known risk factors are African descent, obesity, polycystic ovary syndrome, diabetes, hypertension, and never having given birth. […] It is believed that estrogen and progesterone have a mitogenic effect on leiomyoma cells and also act by influencing (directly and indirectly) a large number of growth factors, cytokines and apoptotic factors as well as other hormones. Furthermore, the actions of estrogen and progesterone are modulated by the cross-talk between estrogen, progesterone and prolactin signaling which controls the expression of the respective nuclear receptors. It is believed that estrogen promotes growth by up-regulating IGF-1, EGFR, TGF-beta1, TGF-beta3 and PDGF, and promotes aberrant survival of leiomyoma cells by down-regulating p53, increasing expression of the anti-apoptotic factor PCP4 and antagonizing PPAR-gamma signaling. Progesterone is thought to promote the growth of leiomyoma through up-regulating EGF, TGF-beta1 and TGF-beta3, and promotes survival through up-regulating Bcl-2 expression and down-regulating TNF-alpha. Progesterone is believed to counteract growth by downregulating IGF-1.

• #14 Uterine Leiomyomata – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK546680/

  Uterine leiomyomata, also known as uterine fibroids, are the most common benign gynecologic tumors, occurring in 50% to 70% of females by menopause, with rates reaching over 80% in Black women. […] Leiomyomata originate from uterine smooth muscle cells in the myometrium, and their growth is primarily stimulated by circulating estrogen. […] Several molecular studies have identified specific gene mutations associated with leiomyomata, the most common of which is the MED12 gene located on chromosome X at position q13. […] The MED12 gene codes for one of the key proteins in the mediator complex (subunit 12) that regulates RNA polymerase II; a mutation in this gene occurs in approximately 70% of uterine leiomyomas. […] Additionally, uterine leiomyomata are hormonally sensitive tumors, and evidence has demonstrated that leiomyomas overexpress certain estrogen and progesterone receptors when compared to normal surrounding myometrium.

• #15 RISING STARS: Role of MED12 mutation in the pathogenesis of uterine fibroids in: Journal of Molecular Endocrinology Volume 71 Issue 4 (2023)

  https://jme.bioscientifica.com/view/journals/jme/71/4/JME-23-0039.xml

  Driver gene mutations occur early in tumorigenesis and significantly affect tumors development and subsequent progress. Four distinct driver gene mutations have been identified in UFs: mutations in MED12, overexpression of high mobility group AT-hook 2 (HMGA2) caused by chromosomal rearrangement, biallelic loss of fumarate hydratase (FH), and deletions of collagen type 4 alpha 5 chain (COL4A5)-collagen type 4 alpha 6 chain (COL4A6). Somatic mutations in MED12, the Mediator complex subunit 12 gene, are frequently observed in 50-80% of UFs. […] Although the precise mechanisms of why they frequently occur in UFs remain unknown, a recent study revealed that oxidative stress induced gene mutations in myometrial cells in vitro. […] The MED12-UFs have distinct characteristics compared with wt-UFs and adjacent myometrial tissues. They occur in a multiple rather than solitary manner. Mutations in MED12 are frequently observed even in small-sized UFs with a diameter of 3.0 cm, consistent with driver gene mutations.

• #16 RISING STARS: Role of MED12 mutation in the pathogenesis of uterine fibroids in: Journal of Molecular Endocrinology Volume 71 Issue 4 (2023)

  https://jme.bioscientifica.com/view/journals/jme/71/4/JME-23-0039.xml

  Uterine fibroids (UFs) are benign tumors arising from the uterus, characterized by accumulation of abundant extracellular matrix (ECM) and sex steroid-dependent growth. Among the driver gene mutations identified in UFs, mutations in MED12, a component of the cyclin-dependent kinase (CDK) Mediator module, are the most common and observed in 50-80% of UFs. They are gain-of-function mutations and are more frequently observed in Black women and commonly observed even in small UFs. MED12 mutation-positive UFs (MED12-UFs) often develop multiple rather than solitary and have distinct gene expression profiles, DNA methylomes, transcriptomes, and proteomes. Gene expressions related to ECM organization and collagen-rich ECM components are upregulated, and impaired Mediator kinase activity and dysregulation of Wnt/-catenin signaling are identified in MED12-UFs. Understanding of characteristics of MED12-UFs and functions of MED12 mutations for UF tumorigenesis may elucidate the pathophysiology of UFs, leading to the development of new therapeutic options in women with symptomatic UFs.

• #17 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  The adipose tissue converts adrenal and ovarian androgens into estrogens, whereas several mechanisms associated with obesity lead to decreased synthesis of sex hormone binding globulin. […] Several studies have revealed that smoking may reduce the incidence of myomas; nicotine inhibits aromatase and reduces the conversion of androgens to estrone. […] An early menarche, before the age of 10, has been found to be a risk factor for uterine myomas, while a menarche over the age of 16 seems to decrease the same risk. […] The HMGA2 gene was found in translocation 12:14, the most common cytogenetic abnormality, that occurs in about 20% of chromosomally abnormal lesions. […] Recent studies described that 70% of fibroids contained a series of mutations in a transcriptional regulator complex subunit 12 (MED12).

• #18 RISING STARS: Role of MED12 mutation in the pathogenesis of uterine fibroids in: Journal of Molecular Endocrinology Volume 71 Issue 4 (2023)

  https://jme.bioscientifica.com/view/journals/jme/71/4/JME-23-0039.xml

  Driver gene mutations occur early in tumorigenesis and significantly affect tumors development and subsequent progress. Four distinct driver gene mutations have been identified in UFs: mutations in MED12, overexpression of high mobility group AT-hook 2 (HMGA2) caused by chromosomal rearrangement, biallelic loss of fumarate hydratase (FH), and deletions of collagen type 4 alpha 5 chain (COL4A5)-collagen type 4 alpha 6 chain (COL4A6). Somatic mutations in MED12, the Mediator complex subunit 12 gene, are frequently observed in 50-80% of UFs. […] Although the precise mechanisms of why they frequently occur in UFs remain unknown, a recent study revealed that oxidative stress induced gene mutations in myometrial cells in vitro. […] The MED12-UFs have distinct characteristics compared with wt-UFs and adjacent myometrial tissues. They occur in a multiple rather than solitary manner. Mutations in MED12 are frequently observed even in small-sized UFs with a diameter of 3.0 cm, consistent with driver gene mutations.

• #19 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  Research for the pathogenesis of fibroids and abnormal extracellular matrix (ECM) led to the analysis of a growth factor with profibrotic activity, transforming growth factor (TGF-). […] Epigenetic changes have also been implicated in leiomyoma formation. […] Uterine leiomyoma growth is strictly related to estrogens and their receptors. […] Leiomyoma growth is influenced by progesterone interaction with some growth factors; it upregulates the EGF (mitogenic) and transforming growth factor- (TGF-)3 (bimodal action). […] Several growth factors, such as vascular endothelial growth factor (VEGF), EGF, heparin binding epidermal growth factor (HB-EGF), PDGF, IGF, TGF-, TGF-, acidic fibroblast growth factor (aFGF), and basic fibroblast growth factor (bFGF), and their respective receptors have been demonstrated to play a role in leiomyoma growth.

• #20 Uterine Fibroids Review: Understanding their Origins to Better Un

  https://www.longdom.org/open-access/uterine-fibroids-review-understanding-their-origins-to-better-understand-their-future-treatments-42568.html

  Recent studies have confirmed that the different cell types contained in fibroids are all clonally derived from a parental cell with implied multipotent stem cell properties. […] 40-50% of fibroids contain chromosomal, karyotypic and cytogenetic abnormalities that are not random or tumor specific. The genes most frequently involved in the genesis of fibroids are (MED12) and high mobility group AT-hook 2 (HMGA2). […] Ethnicity also strongly influences the development and clinical severity of fibroids. […] Many Growth factors and their respective receptors have been implicated in fibroid growth. Myomas are characterized by abnormalities in ECM components and can serve as a reservoir for mediators produced by these altered cells (fibroid growth can be partially mediated via autocrine and paracrine mechanisms).

• #21 RISING STARS: Role of MED12 mutation in the pathogenesis of uterine fibroids in: Journal of Molecular Endocrinology Volume 71 Issue 4 (2023)

  https://jme.bioscientifica.com/view/journals/jme/71/4/JME-23-0039.xml

  Integrative analyses have revealed altered gene expression profiles and DNA methylation status based on the MED12 mutation status in UFs. MED12-UFs have distinct DNA methylome and transcriptome compared to those of wt-UFs and adjacent myometrium. […] Clinically, the MED12 mutation status influences the effects of hormone therapy for UFs. MED12-UFs became smaller in response to ulipristal acetate, a selective progesterone receptor (PR) modulator that shrinks UFs, as compared to HMGA2 overexpressing UFs. […] Whole exome sequencing revealed that hot spots of the mutations in MED12 are located on exon 2, and missense mutations in codons 35, 43, and 44 are frequently observed in UFs. […] MED12 is a component of the kinase module of the Mediator, which consists of cyclin-dependent kinase 8 (CDK8), cyclin C, and the MED12 and MED13 subunits. MED12 activates the kinase activity of the CDK8 in the Mediator via direct interaction with cyclin C, and the Mediator kinase activity is selectively disrupted in MED12-UFs.

• #22 Progesterone Signaling and Uterine Fibroid Pathogenesis; Molecular Mechanisms and Potential Therapeutics

  https://www.mdpi.com/2073-4409/12/8/1117

  Although the leading causes of fibroids are unknown, accumulating epidemiological, clinical, and experimental evidence supports the pivotal role of ovarian steroid hormones in the growth and pathogenesis of UFs. […] Importantly, progesterone action is complex and involves interaction with receptors, transcription factors, kinase proteins, growth factors, and numerous autocrine and paracrine factors. […] The promising results of utilizing selective progesterone receptor modulators (SPRM) in controlling UF-associated symptoms such as bleeding as well as tumor shrinkage, further supports the role progesterone plays in UF pathogenesis. […] Disrupted progesterone signaling is causally linked to many reproductive diseases that result in subfertility or infertility, including UF. […] Studies demonstrated that progesterone signaling promotes the growth and proliferation of fibroid cells through increasing proliferating cell nuclear antigen (PCNA) expression, which increases both the number of fibroid cells and the size of fibroid tumors.

• #23 Hormones and pathogenesis of uterine fibroids | Obgyn Key

  https://obgynkey.com/hormones-and-pathogenesis-of-uterine-fibroids/

  The role of ovarian steroid hormones in the pathogenesis of uterine fibroids is supported by epidemiological, clinical, and experimental evidence. Estradiol and progesterone induce mature leiomyoma cells to release mitogenic stimuli to adjacent immature cells, thereby providing uterine leiomyoma with undifferentiated cells that are likely to support tumor growth. […] The pivotal role of ovarian steroid hormones in the pathogenesis of uterine fibroids is supported by epidemiological, clinical, and experimental evidence. The effects of estradiol and progesterone are interrelated and involve the mediation of receptors, transcription factors, kinase proteins, growth factors, and numerous autocrine and paracrine factors. […] A more accurate analysis of clinical and translational evidence, however, has revealed that progesterone action is required for the full development and proliferation of leiomyoma cells and that estrogen is also necessary, but especially to increase tissue sensitivity to progesterone by increasing the availability of PR.

• #24 Uterine Leiomyomata – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK546680/

  Uterine leiomyomata, also known as uterine fibroids, are the most common benign gynecologic tumors, occurring in 50% to 70% of females by menopause, with rates reaching over 80% in Black women. […] Leiomyomata originate from uterine smooth muscle cells in the myometrium, and their growth is primarily stimulated by circulating estrogen. […] Several molecular studies have identified specific gene mutations associated with leiomyomata, the most common of which is the MED12 gene located on chromosome X at position q13. […] The MED12 gene codes for one of the key proteins in the mediator complex (subunit 12) that regulates RNA polymerase II; a mutation in this gene occurs in approximately 70% of uterine leiomyomas. […] Additionally, uterine leiomyomata are hormonally sensitive tumors, and evidence has demonstrated that leiomyomas overexpress certain estrogen and progesterone receptors when compared to normal surrounding myometrium.

• #25 Uterine fibroid – Wikipedia

  https://en.wikipedia.org/wiki/Uterine_fibroid

  Fibroids are monoclonal tumors and approximately 4050% show karyotypically detectable chromosomal abnormalities. When multiple fibroids are present they frequently have unrelated genetic defects. Specific mutations of the MED12 protein have been noted in 70 percent of fibroids. […] The exact cause of fibroids is not clearly understood, but the current working hypothesis is that genetic predispositions, prenatal hormone exposure and the effects of hormones, growth factors and xenoestrogens cause fibroid growth. Known risk factors are African descent, obesity, polycystic ovary syndrome, diabetes, hypertension, and never having given birth. […] It is believed that estrogen and progesterone have a mitogenic effect on leiomyoma cells and also act by influencing (directly and indirectly) a large number of growth factors, cytokines and apoptotic factors as well as other hormones. Furthermore, the actions of estrogen and progesterone are modulated by the cross-talk between estrogen, progesterone and prolactin signaling which controls the expression of the respective nuclear receptors. It is believed that estrogen promotes growth by up-regulating IGF-1, EGFR, TGF-beta1, TGF-beta3 and PDGF, and promotes aberrant survival of leiomyoma cells by down-regulating p53, increasing expression of the anti-apoptotic factor PCP4 and antagonizing PPAR-gamma signaling. Progesterone is thought to promote the growth of leiomyoma through up-regulating EGF, TGF-beta1 and TGF-beta3, and promotes survival through up-regulating Bcl-2 expression and down-regulating TNF-alpha. Progesterone is believed to counteract growth by downregulating IGF-1.

• #26

  https://rrmedicine.ru/journal/article/2390/

  There is ample evidence that female sex hormones, particularly estrogen, play an important role in pathogenesis of the disease. […] Estrogen has been implicated in pathophysiology of UL due to its pronounced effect on expression of various genes involved in control of cell growth and apoptosis. […] The elevated level of estrogen in UL patients may result from two sources. The first is estrogen in the bloodstream, while the second is estrogen synthesized in the fibroid tissue through conversion of androgens by aromatase. […] This source of estrogen is sufficient for maintaining the growth of the fibroid tissue even without supply of estrogen from other sources. […] Estrogen contributes to the growth of UL through several mechanisms. On the one hand, it increases responsiveness of the cell to progesterone, which in turn up-regulates the expression of proliferating cell nuclear antigen (PCNA) and epidermal growth factor (EGF). On the other hand, estrogen affects the expression of various growth factors and apoptosis-related genes.

• #27 Uterine fibroid – Wikipedia

  https://en.wikipedia.org/wiki/Uterine_fibroid

  Fibroids are monoclonal tumors and approximately 4050% show karyotypically detectable chromosomal abnormalities. When multiple fibroids are present they frequently have unrelated genetic defects. Specific mutations of the MED12 protein have been noted in 70 percent of fibroids. […] The exact cause of fibroids is not clearly understood, but the current working hypothesis is that genetic predispositions, prenatal hormone exposure and the effects of hormones, growth factors and xenoestrogens cause fibroid growth. Known risk factors are African descent, obesity, polycystic ovary syndrome, diabetes, hypertension, and never having given birth. […] It is believed that estrogen and progesterone have a mitogenic effect on leiomyoma cells and also act by influencing (directly and indirectly) a large number of growth factors, cytokines and apoptotic factors as well as other hormones. Furthermore, the actions of estrogen and progesterone are modulated by the cross-talk between estrogen, progesterone and prolactin signaling which controls the expression of the respective nuclear receptors. It is believed that estrogen promotes growth by up-regulating IGF-1, EGFR, TGF-beta1, TGF-beta3 and PDGF, and promotes aberrant survival of leiomyoma cells by down-regulating p53, increasing expression of the anti-apoptotic factor PCP4 and antagonizing PPAR-gamma signaling. Progesterone is thought to promote the growth of leiomyoma through up-regulating EGF, TGF-beta1 and TGF-beta3, and promotes survival through up-regulating Bcl-2 expression and down-regulating TNF-alpha. Progesterone is believed to counteract growth by downregulating IGF-1.

• #28 Hormones and pathogenesis of uterine fibroids | Obgyn Key

  https://obgynkey.com/hormones-and-pathogenesis-of-uterine-fibroids/

  The role of ovarian steroid hormones in the pathogenesis of uterine fibroids is supported by epidemiological, clinical, and experimental evidence. Estradiol and progesterone induce mature leiomyoma cells to release mitogenic stimuli to adjacent immature cells, thereby providing uterine leiomyoma with undifferentiated cells that are likely to support tumor growth. […] The pivotal role of ovarian steroid hormones in the pathogenesis of uterine fibroids is supported by epidemiological, clinical, and experimental evidence. The effects of estradiol and progesterone are interrelated and involve the mediation of receptors, transcription factors, kinase proteins, growth factors, and numerous autocrine and paracrine factors. […] A more accurate analysis of clinical and translational evidence, however, has revealed that progesterone action is required for the full development and proliferation of leiomyoma cells and that estrogen is also necessary, but especially to increase tissue sensitivity to progesterone by increasing the availability of PR.

• #29

  https://rrmedicine.ru/journal/article/2390/

  There is ample evidence that female sex hormones, particularly estrogen, play an important role in pathogenesis of the disease. […] Estrogen has been implicated in pathophysiology of UL due to its pronounced effect on expression of various genes involved in control of cell growth and apoptosis. […] The elevated level of estrogen in UL patients may result from two sources. The first is estrogen in the bloodstream, while the second is estrogen synthesized in the fibroid tissue through conversion of androgens by aromatase. […] This source of estrogen is sufficient for maintaining the growth of the fibroid tissue even without supply of estrogen from other sources. […] Estrogen contributes to the growth of UL through several mechanisms. On the one hand, it increases responsiveness of the cell to progesterone, which in turn up-regulates the expression of proliferating cell nuclear antigen (PCNA) and epidermal growth factor (EGF). On the other hand, estrogen affects the expression of various growth factors and apoptosis-related genes.

• #30

  https://rrmedicine.ru/journal/article/2390/

  There is ample evidence that female sex hormones, particularly estrogen, play an important role in pathogenesis of the disease. […] Estrogen has been implicated in pathophysiology of UL due to its pronounced effect on expression of various genes involved in control of cell growth and apoptosis. […] The elevated level of estrogen in UL patients may result from two sources. The first is estrogen in the bloodstream, while the second is estrogen synthesized in the fibroid tissue through conversion of androgens by aromatase. […] This source of estrogen is sufficient for maintaining the growth of the fibroid tissue even without supply of estrogen from other sources. […] Estrogen contributes to the growth of UL through several mechanisms. On the one hand, it increases responsiveness of the cell to progesterone, which in turn up-regulates the expression of proliferating cell nuclear antigen (PCNA) and epidermal growth factor (EGF). On the other hand, estrogen affects the expression of various growth factors and apoptosis-related genes.

• #31 Progesterone Signaling and Uterine Fibroid Pathogenesis; Molecular Mechanisms and Potential Therapeutics

  https://www.mdpi.com/2073-4409/12/8/1117

  Although the leading causes of fibroids are unknown, accumulating epidemiological, clinical, and experimental evidence supports the pivotal role of ovarian steroid hormones in the growth and pathogenesis of UFs. […] Importantly, progesterone action is complex and involves interaction with receptors, transcription factors, kinase proteins, growth factors, and numerous autocrine and paracrine factors. […] The promising results of utilizing selective progesterone receptor modulators (SPRM) in controlling UF-associated symptoms such as bleeding as well as tumor shrinkage, further supports the role progesterone plays in UF pathogenesis. […] Disrupted progesterone signaling is causally linked to many reproductive diseases that result in subfertility or infertility, including UF. […] Studies demonstrated that progesterone signaling promotes the growth and proliferation of fibroid cells through increasing proliferating cell nuclear antigen (PCNA) expression, which increases both the number of fibroid cells and the size of fibroid tumors.

• #32 Uterine Fibroids Review: Understanding their Origins to Better Un

  https://www.longdom.org/open-access/uterine-fibroids-review-understanding-their-origins-to-better-understand-their-future-treatments-42568.html

  The available evidence continues to reinforce the importance of progesterone in the development of fibroids (suggesting that estrogens are required, but not sufficient, to stimulate fibroid proliferation). […] The Ulipristal Acetate mediated volume reduction is due to a series of multifactorial and successive events that lead to a low proliferation rate, a transient stimulation of cell death that is not dependent on caspase 3 and a dramatic reduction in the ECM (especially notable after long-term treatment), which could be partially explained by the increased MMP2 expression.

• #33 Progesterone Signaling and Uterine Fibroid Pathogenesis; Molecular Mechanisms and Potential Therapeutics

  https://www.mdpi.com/2073-4409/12/8/1117

  Although the leading causes of fibroids are unknown, accumulating epidemiological, clinical, and experimental evidence supports the pivotal role of ovarian steroid hormones in the growth and pathogenesis of UFs. […] Importantly, progesterone action is complex and involves interaction with receptors, transcription factors, kinase proteins, growth factors, and numerous autocrine and paracrine factors. […] The promising results of utilizing selective progesterone receptor modulators (SPRM) in controlling UF-associated symptoms such as bleeding as well as tumor shrinkage, further supports the role progesterone plays in UF pathogenesis. […] Disrupted progesterone signaling is causally linked to many reproductive diseases that result in subfertility or infertility, including UF. […] Studies demonstrated that progesterone signaling promotes the growth and proliferation of fibroid cells through increasing proliferating cell nuclear antigen (PCNA) expression, which increases both the number of fibroid cells and the size of fibroid tumors.

• #34 Uterine fibroid – Wikipedia

  https://en.wikipedia.org/wiki/Uterine_fibroid

  Fibroids are monoclonal tumors and approximately 4050% show karyotypically detectable chromosomal abnormalities. When multiple fibroids are present they frequently have unrelated genetic defects. Specific mutations of the MED12 protein have been noted in 70 percent of fibroids. […] The exact cause of fibroids is not clearly understood, but the current working hypothesis is that genetic predispositions, prenatal hormone exposure and the effects of hormones, growth factors and xenoestrogens cause fibroid growth. Known risk factors are African descent, obesity, polycystic ovary syndrome, diabetes, hypertension, and never having given birth. […] It is believed that estrogen and progesterone have a mitogenic effect on leiomyoma cells and also act by influencing (directly and indirectly) a large number of growth factors, cytokines and apoptotic factors as well as other hormones. Furthermore, the actions of estrogen and progesterone are modulated by the cross-talk between estrogen, progesterone and prolactin signaling which controls the expression of the respective nuclear receptors. It is believed that estrogen promotes growth by up-regulating IGF-1, EGFR, TGF-beta1, TGF-beta3 and PDGF, and promotes aberrant survival of leiomyoma cells by down-regulating p53, increasing expression of the anti-apoptotic factor PCP4 and antagonizing PPAR-gamma signaling. Progesterone is thought to promote the growth of leiomyoma through up-regulating EGF, TGF-beta1 and TGF-beta3, and promotes survival through up-regulating Bcl-2 expression and down-regulating TNF-alpha. Progesterone is believed to counteract growth by downregulating IGF-1.

• #35 Uterine fibroid – Wikipedia

  https://en.wikipedia.org/wiki/Uterine_fibroid

  Fibroids are monoclonal tumors and approximately 4050% show karyotypically detectable chromosomal abnormalities. When multiple fibroids are present they frequently have unrelated genetic defects. Specific mutations of the MED12 protein have been noted in 70 percent of fibroids. […] The exact cause of fibroids is not clearly understood, but the current working hypothesis is that genetic predispositions, prenatal hormone exposure and the effects of hormones, growth factors and xenoestrogens cause fibroid growth. Known risk factors are African descent, obesity, polycystic ovary syndrome, diabetes, hypertension, and never having given birth. […] It is believed that estrogen and progesterone have a mitogenic effect on leiomyoma cells and also act by influencing (directly and indirectly) a large number of growth factors, cytokines and apoptotic factors as well as other hormones. Furthermore, the actions of estrogen and progesterone are modulated by the cross-talk between estrogen, progesterone and prolactin signaling which controls the expression of the respective nuclear receptors. It is believed that estrogen promotes growth by up-regulating IGF-1, EGFR, TGF-beta1, TGF-beta3 and PDGF, and promotes aberrant survival of leiomyoma cells by down-regulating p53, increasing expression of the anti-apoptotic factor PCP4 and antagonizing PPAR-gamma signaling. Progesterone is thought to promote the growth of leiomyoma through up-regulating EGF, TGF-beta1 and TGF-beta3, and promotes survival through up-regulating Bcl-2 expression and down-regulating TNF-alpha. Progesterone is believed to counteract growth by downregulating IGF-1.

• #36 New Insights into Molecular Pathogenesis of Uterine Fibroids: From the Lab to a Clinician-Friendly Review | IntechOpen

  https://www.intechopen.com/chapters/1165825

  In recent years, many advances have been made, allowing us to understand the molecular mechanisms underlying the pathogenesis of UFs. […] It has been hypothesized that uterine hypoxia, aberrant methylation, or abnormal estrogen signaling could play a critical role in the transformation of a myometrial stem cell into a TIC. […] It has been demonstrated that paracrine activation of the wingless-type (Wnt)/-catenin pathway mediated by estrogen and progesterone has a critical role in enhancing the growth and proliferation of leiomyoma stem cells. […] The presence of steroid hormones stimulates the secretion of Wnt ligands from mature myometrium or leiomyoma cells. […] The development of clinical disease is dependent on a paracrine mechanism and a multistep process from transformation to the fibroid progenitor through to growth acceleration.

• #37 Uterine fibroid – Wikipedia

  https://en.wikipedia.org/wiki/Uterine_fibroid

  Fibroids are monoclonal tumors and approximately 4050% show karyotypically detectable chromosomal abnormalities. When multiple fibroids are present they frequently have unrelated genetic defects. Specific mutations of the MED12 protein have been noted in 70 percent of fibroids. […] The exact cause of fibroids is not clearly understood, but the current working hypothesis is that genetic predispositions, prenatal hormone exposure and the effects of hormones, growth factors and xenoestrogens cause fibroid growth. Known risk factors are African descent, obesity, polycystic ovary syndrome, diabetes, hypertension, and never having given birth. […] It is believed that estrogen and progesterone have a mitogenic effect on leiomyoma cells and also act by influencing (directly and indirectly) a large number of growth factors, cytokines and apoptotic factors as well as other hormones. Furthermore, the actions of estrogen and progesterone are modulated by the cross-talk between estrogen, progesterone and prolactin signaling which controls the expression of the respective nuclear receptors. It is believed that estrogen promotes growth by up-regulating IGF-1, EGFR, TGF-beta1, TGF-beta3 and PDGF, and promotes aberrant survival of leiomyoma cells by down-regulating p53, increasing expression of the anti-apoptotic factor PCP4 and antagonizing PPAR-gamma signaling. Progesterone is thought to promote the growth of leiomyoma through up-regulating EGF, TGF-beta1 and TGF-beta3, and promotes survival through up-regulating Bcl-2 expression and down-regulating TNF-alpha. Progesterone is believed to counteract growth by downregulating IGF-1.

• #38 Progesterone Signaling and Uterine Fibroid Pathogenesis; Molecular Mechanisms and Potential Therapeutics

  https://www.mdpi.com/2073-4409/12/8/1117

  Although the leading causes of fibroids are unknown, accumulating epidemiological, clinical, and experimental evidence supports the pivotal role of ovarian steroid hormones in the growth and pathogenesis of UFs. […] Importantly, progesterone action is complex and involves interaction with receptors, transcription factors, kinase proteins, growth factors, and numerous autocrine and paracrine factors. […] The promising results of utilizing selective progesterone receptor modulators (SPRM) in controlling UF-associated symptoms such as bleeding as well as tumor shrinkage, further supports the role progesterone plays in UF pathogenesis. […] Disrupted progesterone signaling is causally linked to many reproductive diseases that result in subfertility or infertility, including UF. […] Studies demonstrated that progesterone signaling promotes the growth and proliferation of fibroid cells through increasing proliferating cell nuclear antigen (PCNA) expression, which increases both the number of fibroid cells and the size of fibroid tumors.

• #39 Progesterone Signaling and Uterine Fibroid Pathogenesis; Molecular Mechanisms and Potential Therapeutics

  https://www.mdpi.com/2073-4409/12/8/1117

  Although the leading causes of fibroids are unknown, accumulating epidemiological, clinical, and experimental evidence supports the pivotal role of ovarian steroid hormones in the growth and pathogenesis of UFs. […] Importantly, progesterone action is complex and involves interaction with receptors, transcription factors, kinase proteins, growth factors, and numerous autocrine and paracrine factors. […] The promising results of utilizing selective progesterone receptor modulators (SPRM) in controlling UF-associated symptoms such as bleeding as well as tumor shrinkage, further supports the role progesterone plays in UF pathogenesis. […] Disrupted progesterone signaling is causally linked to many reproductive diseases that result in subfertility or infertility, including UF. […] Studies demonstrated that progesterone signaling promotes the growth and proliferation of fibroid cells through increasing proliferating cell nuclear antigen (PCNA) expression, which increases both the number of fibroid cells and the size of fibroid tumors.

• #40 Hormones and pathogenesis of uterine fibroids | Obgyn Key

  https://obgynkey.com/hormones-and-pathogenesis-of-uterine-fibroids/

  The blockade of pituitary gonadotropin release with gonadotropin-releasing hormone (GnRH) analogs or antagonist is an effective strategy to control fibroid symptoms and arrest their growth. […] The most probable explanation for the effectiveness of this therapy is ovarian blockade and the consequent decrease in circulating estradiol and progesterone levels. […] Mifepristone, asoprisnil, and ulipristal are selective PR modulators that have been shown in clinical trials to inhibit fibroid growth.

• #41 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  Research for the pathogenesis of fibroids and abnormal extracellular matrix (ECM) led to the analysis of a growth factor with profibrotic activity, transforming growth factor (TGF-). […] Epigenetic changes have also been implicated in leiomyoma formation. […] Uterine leiomyoma growth is strictly related to estrogens and their receptors. […] Leiomyoma growth is influenced by progesterone interaction with some growth factors; it upregulates the EGF (mitogenic) and transforming growth factor- (TGF-)3 (bimodal action). […] Several growth factors, such as vascular endothelial growth factor (VEGF), EGF, heparin binding epidermal growth factor (HB-EGF), PDGF, IGF, TGF-, TGF-, acidic fibroblast growth factor (aFGF), and basic fibroblast growth factor (bFGF), and their respective receptors have been demonstrated to play a role in leiomyoma growth.

• #42 Uterine fibroid: from pathogenesis to clinical management | Obgyn Key

  https://obgynkey.com/uterine-fibroid-from-pathogenesis-to-clinical-management/

  Uterine fibroid or leiomyoma is the most common benign gynecological tumor in premenopausal women (1525%). […] The hypothesis of generation of leiomyoma stem cells, the role of epigenetic/cytogenetic anomalies/mutations, and the overexpression of micro-RNA are of great interest in exploring increased cell proliferation and excessive formation of extracellular matrix. […] The role of sex steroid hormones (estrogens, progesterone) still remains a key point in the pathogenesis of uterine leiomyoma, and, particularly, estrogen receptors (ERs) and progesterone receptors (PRs) play a role in the development and maintenance of tumor growth, and new receptor modulators are attractive for the medical treatment of uterine fibroid. […] Estrogens and progesterone act via a large group of growth factors (in particular, the family of transforming growth factor beta (TGFB)), which in turn by activation of multiple signaling pathways regulate major cellular processes, including proliferation, angiogenesis and fibrosis; these have stimulated an interest toward the development of new drugs. […] Future studies should focus on the use of different alternative procedures (MRI-guided, US laser) and the development of new SPRM or novel non-hormonal drugs, thereby increasing the possibility of tailoring the treatment of uterine fibroids.

• #43 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  Research for the pathogenesis of fibroids and abnormal extracellular matrix (ECM) led to the analysis of a growth factor with profibrotic activity, transforming growth factor (TGF-). […] Epigenetic changes have also been implicated in leiomyoma formation. […] Uterine leiomyoma growth is strictly related to estrogens and their receptors. […] Leiomyoma growth is influenced by progesterone interaction with some growth factors; it upregulates the EGF (mitogenic) and transforming growth factor- (TGF-)3 (bimodal action). […] Several growth factors, such as vascular endothelial growth factor (VEGF), EGF, heparin binding epidermal growth factor (HB-EGF), PDGF, IGF, TGF-, TGF-, acidic fibroblast growth factor (aFGF), and basic fibroblast growth factor (bFGF), and their respective receptors have been demonstrated to play a role in leiomyoma growth.

• #44 Update on the Role and Regulatory Mechanism of Extracellular Matrix in the Pathogenesis of Uterine Fibroids

  https://www.mdpi.com/1422-0067/24/6/5778

  Numerous studies demonstrated that TGF-β signaling plays an important role in the pathogenesis of UFs. […] Abnormal ECM accumulation and deposition have been shown to be associated with the activation of TGF-β signaling in UFs. […] The ECM acts as a reservoir of profibrotic growth factors and enhances their activity by increasing their stability and prolonging signaling duration. […] The significant variations in the quantity and distribution of the ECM also create variation in the degree of UF tissue stiffness from soft to firm to solid to hard, with a major impact on the gene expression and biology of these tumor lesions. […] Pharmacological drugs can suppress the UF phenotype by inhibiting ECM production via multiple mechanisms, including epigenetics. […] However, several aspects need to be further elucidated, including characterizing the functional interaction of ECM-secreted cells with other types of cells, elucidating the impact of ECM on the microenvironment, and investigating the molecular and functional structure of ECM that regulates mechanotransduction and stiffness in both UFs and the at-risk MM.

• #45 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  Research for the pathogenesis of fibroids and abnormal extracellular matrix (ECM) led to the analysis of a growth factor with profibrotic activity, transforming growth factor (TGF-). […] Epigenetic changes have also been implicated in leiomyoma formation. […] Uterine leiomyoma growth is strictly related to estrogens and their receptors. […] Leiomyoma growth is influenced by progesterone interaction with some growth factors; it upregulates the EGF (mitogenic) and transforming growth factor- (TGF-)3 (bimodal action). […] Several growth factors, such as vascular endothelial growth factor (VEGF), EGF, heparin binding epidermal growth factor (HB-EGF), PDGF, IGF, TGF-, TGF-, acidic fibroblast growth factor (aFGF), and basic fibroblast growth factor (bFGF), and their respective receptors have been demonstrated to play a role in leiomyoma growth.

• #46 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  Research for the pathogenesis of fibroids and abnormal extracellular matrix (ECM) led to the analysis of a growth factor with profibrotic activity, transforming growth factor (TGF-). […] Epigenetic changes have also been implicated in leiomyoma formation. […] Uterine leiomyoma growth is strictly related to estrogens and their receptors. […] Leiomyoma growth is influenced by progesterone interaction with some growth factors; it upregulates the EGF (mitogenic) and transforming growth factor- (TGF-)3 (bimodal action). […] Several growth factors, such as vascular endothelial growth factor (VEGF), EGF, heparin binding epidermal growth factor (HB-EGF), PDGF, IGF, TGF-, TGF-, acidic fibroblast growth factor (aFGF), and basic fibroblast growth factor (bFGF), and their respective receptors have been demonstrated to play a role in leiomyoma growth.

• #47 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  Research for the pathogenesis of fibroids and abnormal extracellular matrix (ECM) led to the analysis of a growth factor with profibrotic activity, transforming growth factor (TGF-). […] Epigenetic changes have also been implicated in leiomyoma formation. […] Uterine leiomyoma growth is strictly related to estrogens and their receptors. […] Leiomyoma growth is influenced by progesterone interaction with some growth factors; it upregulates the EGF (mitogenic) and transforming growth factor- (TGF-)3 (bimodal action). […] Several growth factors, such as vascular endothelial growth factor (VEGF), EGF, heparin binding epidermal growth factor (HB-EGF), PDGF, IGF, TGF-, TGF-, acidic fibroblast growth factor (aFGF), and basic fibroblast growth factor (bFGF), and their respective receptors have been demonstrated to play a role in leiomyoma growth.

• #48 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  Research for the pathogenesis of fibroids and abnormal extracellular matrix (ECM) led to the analysis of a growth factor with profibrotic activity, transforming growth factor (TGF-). […] Epigenetic changes have also been implicated in leiomyoma formation. […] Uterine leiomyoma growth is strictly related to estrogens and their receptors. […] Leiomyoma growth is influenced by progesterone interaction with some growth factors; it upregulates the EGF (mitogenic) and transforming growth factor- (TGF-)3 (bimodal action). […] Several growth factors, such as vascular endothelial growth factor (VEGF), EGF, heparin binding epidermal growth factor (HB-EGF), PDGF, IGF, TGF-, TGF-, acidic fibroblast growth factor (aFGF), and basic fibroblast growth factor (bFGF), and their respective receptors have been demonstrated to play a role in leiomyoma growth.

• #49 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  Research for the pathogenesis of fibroids and abnormal extracellular matrix (ECM) led to the analysis of a growth factor with profibrotic activity, transforming growth factor (TGF-). […] Epigenetic changes have also been implicated in leiomyoma formation. […] Uterine leiomyoma growth is strictly related to estrogens and their receptors. […] Leiomyoma growth is influenced by progesterone interaction with some growth factors; it upregulates the EGF (mitogenic) and transforming growth factor- (TGF-)3 (bimodal action). […] Several growth factors, such as vascular endothelial growth factor (VEGF), EGF, heparin binding epidermal growth factor (HB-EGF), PDGF, IGF, TGF-, TGF-, acidic fibroblast growth factor (aFGF), and basic fibroblast growth factor (bFGF), and their respective receptors have been demonstrated to play a role in leiomyoma growth.

• #50 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  Research for the pathogenesis of fibroids and abnormal extracellular matrix (ECM) led to the analysis of a growth factor with profibrotic activity, transforming growth factor (TGF-). […] Epigenetic changes have also been implicated in leiomyoma formation. […] Uterine leiomyoma growth is strictly related to estrogens and their receptors. […] Leiomyoma growth is influenced by progesterone interaction with some growth factors; it upregulates the EGF (mitogenic) and transforming growth factor- (TGF-)3 (bimodal action). […] Several growth factors, such as vascular endothelial growth factor (VEGF), EGF, heparin binding epidermal growth factor (HB-EGF), PDGF, IGF, TGF-, TGF-, acidic fibroblast growth factor (aFGF), and basic fibroblast growth factor (bFGF), and their respective receptors have been demonstrated to play a role in leiomyoma growth.

• #51

  https://www.fibroids.net/pubfart4.html

  This paradigm of dysregulation of growth factor function that results in disruption of normal vascular function appears relevant for non-uterine bleeding disorders. […] Growth factors or their receptors that are differentially regulated in the leiomyomas or the endometrium of leiomyomatous uteri are potential mediators of leiomyoma-related complications. These differentially regulated factors, which are known to act on vascular tissue by increasing proliferation or changing vessel caliber, are potential causes of leiomyoma-related menorrhagia. The factors that meet these criteria include bFGF, vascular endothelial growth factor (VEGF), heparin-binding epidermal growth factor (HBEGF), platelet derived growth factor (PDGF), TGF-b, PTHrP and prolactin. […] Leiomyomas synthesize and store significantly more bFGF than normal myometrium.

• #52 Pathophysiology of uterine fibroids

  https://www.contemporaryobgyn.net/view/pathophysiology-of-uterine-fibroids

  A better understanding of the pathophysiology of uterine fibroids (UFs) will enable healthcare providers to deliver high-quality informed care to their patients, according to Ayman Al-Hendy, MD, PhD, a professor of ob/gyn at Pritzker School of Medicine, University of Chicago. […] Pathophysiology also enables providers to understand the mechanism of action of the various treatment tools, so they can tailor and match an appropriate treatment to a specific patient, Al-Hendy told Contemporary OB/GYN. […] The key pathways are estrogen, progesterone, DNA damage, transforming growth factor beta, growth factors, the canonical Wnt pathway and extracellular matrix (ECM) remodeling. […] But we have limited safe treatment options for fibroid patients who want to preserve their fertility potential, Al-Hendy said. We also do not understand how fibroids cause heavy menstrual bleeding or infertility. […] Investigating genetic correlations and shared loci sheds light on potential causal relationships between reproductive traits and uterine leiomyomata, offering insights into their complex interplay and urging further mechanistic exploration.

• #53

  https://journals.lww.com/md-journal/fulltext/2023/05190/search_for_key_genes,_key_signaling_pathways,_and.56.aspx

  The formation of uterine fibroids is involved in the Wnt/-catenin signaling pathway, and the Wnt/-catenin signaling pathway also has a variety of physiological processes, such as tissue renewal, cell differentiation and proliferation. […] KEGG pathway analysis displayed that key genes were mainly enriched in Cytokine-cytokine receptor interaction, Focal adhesion, Ras signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, Fluid shear stress and atherosclerosis, Regulation of actin cytoskeleton, Rap1 signaling pathway, cAMP signaling pathway and Tight junction. […] Formation of uterine fibroids is associated with chronic inflammatory immune system. Chronic inflammatory immune characteristics can affect the occurrence and development of uterine fibroids because it will lead to an intensified immune system response in the female uterus, which will induce cell proliferation and fibrosis.

• #54 New Insights into Molecular Pathogenesis of Uterine Fibroids: From the Lab to a Clinician-Friendly Review | IntechOpen

  https://www.intechopen.com/chapters/1165825

  In recent years, many advances have been made, allowing us to understand the molecular mechanisms underlying the pathogenesis of UFs. […] It has been hypothesized that uterine hypoxia, aberrant methylation, or abnormal estrogen signaling could play a critical role in the transformation of a myometrial stem cell into a TIC. […] It has been demonstrated that paracrine activation of the wingless-type (Wnt)/-catenin pathway mediated by estrogen and progesterone has a critical role in enhancing the growth and proliferation of leiomyoma stem cells. […] The presence of steroid hormones stimulates the secretion of Wnt ligands from mature myometrium or leiomyoma cells. […] The development of clinical disease is dependent on a paracrine mechanism and a multistep process from transformation to the fibroid progenitor through to growth acceleration.

• #55

  https://journals.lww.com/md-journal/fulltext/2023/05190/search_for_key_genes,_key_signaling_pathways,_and.56.aspx

  The formation of uterine fibroids is involved in the Wnt/-catenin signaling pathway, and the Wnt/-catenin signaling pathway also has a variety of physiological processes, such as tissue renewal, cell differentiation and proliferation. […] KEGG pathway analysis displayed that key genes were mainly enriched in Cytokine-cytokine receptor interaction, Focal adhesion, Ras signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, Fluid shear stress and atherosclerosis, Regulation of actin cytoskeleton, Rap1 signaling pathway, cAMP signaling pathway and Tight junction. […] Formation of uterine fibroids is associated with chronic inflammatory immune system. Chronic inflammatory immune characteristics can affect the occurrence and development of uterine fibroids because it will lead to an intensified immune system response in the female uterus, which will induce cell proliferation and fibrosis.

• #56

  https://www-.grantome.com/grant/NIH/R01-HD076450-03

  Uterine fibroids (leiomyomas) are benign smooth muscle cell (SMC) tumors of the myometrium. […] Dysregulated PI3K/AKT pathway leading to the activation of mTOR has been suggested to play an essential role in the pathogenesis of leiomyomas. Our preliminary data suggest that GPR10, a GPCR normally silenced in the periphery by the tumor suppressor REST/ NRSF, is near ubiquitously over-expressed human leiomyomas. Further, REST protein is dramatically reduced in leiomyomas. […] We hypothesize that the loss of REST leads to GPR10 expression in leiomyomas and this aberrant gene expression functionally promotes cell proliferation contributing to the pathogenesis of uterine fibroids. The current project will establish the functional role that the loss of REST has on the pathogenesis of uterine fibroids using in vitro methods and novel in vivo genetic models.

• #57

  https://journals.lww.com/md-journal/fulltext/2023/05190/search_for_key_genes,_key_signaling_pathways,_and.56.aspx

  The formation of uterine fibroids is involved in the Wnt/-catenin signaling pathway, and the Wnt/-catenin signaling pathway also has a variety of physiological processes, such as tissue renewal, cell differentiation and proliferation. […] KEGG pathway analysis displayed that key genes were mainly enriched in Cytokine-cytokine receptor interaction, Focal adhesion, Ras signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, Fluid shear stress and atherosclerosis, Regulation of actin cytoskeleton, Rap1 signaling pathway, cAMP signaling pathway and Tight junction. […] Formation of uterine fibroids is associated with chronic inflammatory immune system. Chronic inflammatory immune characteristics can affect the occurrence and development of uterine fibroids because it will lead to an intensified immune system response in the female uterus, which will induce cell proliferation and fibrosis.

• #58

  https://journals.lww.com/md-journal/fulltext/2023/05190/search_for_key_genes,_key_signaling_pathways,_and.56.aspx

  The formation of uterine fibroids is involved in the Wnt/-catenin signaling pathway, and the Wnt/-catenin signaling pathway also has a variety of physiological processes, such as tissue renewal, cell differentiation and proliferation. […] KEGG pathway analysis displayed that key genes were mainly enriched in Cytokine-cytokine receptor interaction, Focal adhesion, Ras signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, Fluid shear stress and atherosclerosis, Regulation of actin cytoskeleton, Rap1 signaling pathway, cAMP signaling pathway and Tight junction. […] Formation of uterine fibroids is associated with chronic inflammatory immune system. Chronic inflammatory immune characteristics can affect the occurrence and development of uterine fibroids because it will lead to an intensified immune system response in the female uterus, which will induce cell proliferation and fibrosis.

• #59 Vascular biology of uterine fibroids: connecting fibroids and vascular disorders in: Reproduction Volume 162 Issue 2 (2021)

  https://rep.bioscientifica.com/view/journals/rep/162/2/REP-21-0087.xml

  The consistent evidence of the correlation between hypertension and uterine fibroids raises the prospect, once again, of vascular involvement in fibroid pathobiology. […] The hypovascularity of fibroids creates a hypoxic microenvironment that serves as a positive feedback loop driving proliferation and neovascularization. For instance, endothelin-1 (ET-1) is a potent vasoconstrictor peptide secreted by endothelial cells and fibroid smooth muscle cells in response to hypoxia. ET-1 is elevated in the plasma of women with fibroids, compared to those without, and drives fibroid cell proliferation. […] Aberrant activation of the RAA system is implicated in fibroid cell proliferation through the actions of Ang-II and aldosterone. […] Collectively, increased cellular proliferation, decreased apoptosis and enhanced ECM synthesis promote fibroid growth.

• #60 Pathophysiology of uterine fibroids

  https://www.contemporaryobgyn.net/view/pathophysiology-of-uterine-fibroids

  A better understanding of the pathophysiology of uterine fibroids (UFs) will enable healthcare providers to deliver high-quality informed care to their patients, according to Ayman Al-Hendy, MD, PhD, a professor of ob/gyn at Pritzker School of Medicine, University of Chicago. […] Pathophysiology also enables providers to understand the mechanism of action of the various treatment tools, so they can tailor and match an appropriate treatment to a specific patient, Al-Hendy told Contemporary OB/GYN. […] The key pathways are estrogen, progesterone, DNA damage, transforming growth factor beta, growth factors, the canonical Wnt pathway and extracellular matrix (ECM) remodeling. […] But we have limited safe treatment options for fibroid patients who want to preserve their fertility potential, Al-Hendy said. We also do not understand how fibroids cause heavy menstrual bleeding or infertility. […] Investigating genetic correlations and shared loci sheds light on potential causal relationships between reproductive traits and uterine leiomyomata, offering insights into their complex interplay and urging further mechanistic exploration.

• #61

  https://journals.lww.com/md-journal/fulltext/2023/05190/search_for_key_genes,_key_signaling_pathways,_and.56.aspx

  The formation of uterine fibroids is involved in the Wnt/-catenin signaling pathway, and the Wnt/-catenin signaling pathway also has a variety of physiological processes, such as tissue renewal, cell differentiation and proliferation. […] KEGG pathway analysis displayed that key genes were mainly enriched in Cytokine-cytokine receptor interaction, Focal adhesion, Ras signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, Fluid shear stress and atherosclerosis, Regulation of actin cytoskeleton, Rap1 signaling pathway, cAMP signaling pathway and Tight junction. […] Formation of uterine fibroids is associated with chronic inflammatory immune system. Chronic inflammatory immune characteristics can affect the occurrence and development of uterine fibroids because it will lead to an intensified immune system response in the female uterus, which will induce cell proliferation and fibrosis.

• #62 Update on the Role and Regulatory Mechanism of Extracellular Matrix in the Pathogenesis of Uterine Fibroids

  https://www.mdpi.com/1422-0067/24/6/5778

  In addition, we provide the current state of knowledge by discussing the molecular mechanisms underlying the regulation and emerging role of the extracellular matrix in the pathogenesis of UFs and in applications. […] Comprehensive and deeper insights into ECM-mediated alterations and interactions in cellular events will help develop novel strategies to treat patients with this common tumor. […] Several risk factors have been shown to impact UF pathogenesis and are associated with a higher probability of UF formation and development. […] These risk factors affect several key pathways, including inflammation, DNA damage repair pathway, β-catenin pathway, and genetic instability, among others, leading to the pathogenesis of UFs. […] UFs are characterized by the excessive deposition of ECM proteins, such as collagens, fibronectin, and proteoglycans, representing fibrosis.

• #63 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  Many cytokines, including tumor necrosis factor- , erythropoietin, interleukin- (IL-)1, and IL-6, have been implicated in development of uterine leiomyoma. […] Extracellular disorganized matrix is a peculiar characteristic of fibroid growth, mainly consisting of collagen subtypes, fibronectin, and proteoglycans. […] The etiopathology of uterine fibroid remains unclear, multifactorial, and enigmatic. […] Abnormal ECM expression, increased growth factors, cytokines and chemokines concentrations, and an extracellular disorganized matrix have been implicated in development and growth of uterine leiomyomas. […] Endomyometrial junction disruption might play a crucial role on fibroid-related infertility, uterine bleeding, and growth of submucosal and intramural myomas.

• #64 Update on the Role and Regulatory Mechanism of Extracellular Matrix in the Pathogenesis of Uterine Fibroids

  https://www.mdpi.com/1422-0067/24/6/5778

  In addition, we provide the current state of knowledge by discussing the molecular mechanisms underlying the regulation and emerging role of the extracellular matrix in the pathogenesis of UFs and in applications. […] Comprehensive and deeper insights into ECM-mediated alterations and interactions in cellular events will help develop novel strategies to treat patients with this common tumor. […] Several risk factors have been shown to impact UF pathogenesis and are associated with a higher probability of UF formation and development. […] These risk factors affect several key pathways, including inflammation, DNA damage repair pathway, β-catenin pathway, and genetic instability, among others, leading to the pathogenesis of UFs. […] UFs are characterized by the excessive deposition of ECM proteins, such as collagens, fibronectin, and proteoglycans, representing fibrosis.

• #65 Advanced 3D Imaging of Uterine Leiomyoma’s Morphology by Propagation-based Phase-Contrast Microtomography | Scientific Reports

  https://www.nature.com/articles/s41598-019-47048-0

  The role of inflammation and reparative processes as well as the effect of some potential therapeutic compounds on uterine leiomyoma are currently under in vitro investigation. […] The etiology of uterine fibroids indicates that its growth is due to an increase not only of the cell number but also of the ECM amount, both promoted by endocrine and autocrine growth factors. In turns, the alterations in ECM volume and distribution can modify mechanical stress on cells, leading to activation of specific cells signaling that contribute to leiomyoma growth. […] Previous studies showed an impaired expression of collagen, fibronectin and proteoglycans in leiomyoma compared to normal myometrium: in particular, leiomyoma was shown to contain an abnormal collagen fibril structure and orientation, suggesting that the well-regulated fibril formation in myometrium is altered in leiomyomas.

• #66 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  Many cytokines, including tumor necrosis factor- , erythropoietin, interleukin- (IL-)1, and IL-6, have been implicated in development of uterine leiomyoma. […] Extracellular disorganized matrix is a peculiar characteristic of fibroid growth, mainly consisting of collagen subtypes, fibronectin, and proteoglycans. […] The etiopathology of uterine fibroid remains unclear, multifactorial, and enigmatic. […] Abnormal ECM expression, increased growth factors, cytokines and chemokines concentrations, and an extracellular disorganized matrix have been implicated in development and growth of uterine leiomyomas. […] Endomyometrial junction disruption might play a crucial role on fibroid-related infertility, uterine bleeding, and growth of submucosal and intramural myomas.

• #67 Advanced 3D Imaging of Uterine Leiomyoma’s Morphology by Propagation-based Phase-Contrast Microtomography | Scientific Reports

  https://www.nature.com/articles/s41598-019-47048-0

  The role of inflammation and reparative processes as well as the effect of some potential therapeutic compounds on uterine leiomyoma are currently under in vitro investigation. […] The etiology of uterine fibroids indicates that its growth is due to an increase not only of the cell number but also of the ECM amount, both promoted by endocrine and autocrine growth factors. In turns, the alterations in ECM volume and distribution can modify mechanical stress on cells, leading to activation of specific cells signaling that contribute to leiomyoma growth. […] Previous studies showed an impaired expression of collagen, fibronectin and proteoglycans in leiomyoma compared to normal myometrium: in particular, leiomyoma was shown to contain an abnormal collagen fibril structure and orientation, suggesting that the well-regulated fibril formation in myometrium is altered in leiomyomas.

• #68

  https://link.springer.com/article/10.1007/s43032-022-00960-9

  The extracellular matrix (ECM) comprises most of the tumor growth and consists mainly of glycoproteins, collagens, and peptidoglycans. […] Some of the abundant and upregulated proteins in fibroids are collagen type-I, fibronectin, and periostin (POSTN). […] In compliance with that, we showed that CD44/Stro1++ stem cells-derived UF organoids express an elevated level of POSTN compared to the MMSC-derived organoids suggesting that UFSC are predisposed to form uterine fibroids.

• #69 Update on the Role and Regulatory Mechanism of Extracellular Matrix in the Pathogenesis of Uterine Fibroids

  https://www.mdpi.com/1422-0067/24/6/5778

  In addition, we provide the current state of knowledge by discussing the molecular mechanisms underlying the regulation and emerging role of the extracellular matrix in the pathogenesis of UFs and in applications. […] Comprehensive and deeper insights into ECM-mediated alterations and interactions in cellular events will help develop novel strategies to treat patients with this common tumor. […] Several risk factors have been shown to impact UF pathogenesis and are associated with a higher probability of UF formation and development. […] These risk factors affect several key pathways, including inflammation, DNA damage repair pathway, β-catenin pathway, and genetic instability, among others, leading to the pathogenesis of UFs. […] UFs are characterized by the excessive deposition of ECM proteins, such as collagens, fibronectin, and proteoglycans, representing fibrosis.

• #70 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  Many cytokines, including tumor necrosis factor- , erythropoietin, interleukin- (IL-)1, and IL-6, have been implicated in development of uterine leiomyoma. […] Extracellular disorganized matrix is a peculiar characteristic of fibroid growth, mainly consisting of collagen subtypes, fibronectin, and proteoglycans. […] The etiopathology of uterine fibroid remains unclear, multifactorial, and enigmatic. […] Abnormal ECM expression, increased growth factors, cytokines and chemokines concentrations, and an extracellular disorganized matrix have been implicated in development and growth of uterine leiomyomas. […] Endomyometrial junction disruption might play a crucial role on fibroid-related infertility, uterine bleeding, and growth of submucosal and intramural myomas.

• #71 Advanced 3D Imaging of Uterine Leiomyoma’s Morphology by Propagation-based Phase-Contrast Microtomography | Scientific Reports

  https://www.nature.com/articles/s41598-019-47048-0

  The role of inflammation and reparative processes as well as the effect of some potential therapeutic compounds on uterine leiomyoma are currently under in vitro investigation. […] The etiology of uterine fibroids indicates that its growth is due to an increase not only of the cell number but also of the ECM amount, both promoted by endocrine and autocrine growth factors. In turns, the alterations in ECM volume and distribution can modify mechanical stress on cells, leading to activation of specific cells signaling that contribute to leiomyoma growth. […] Previous studies showed an impaired expression of collagen, fibronectin and proteoglycans in leiomyoma compared to normal myometrium: in particular, leiomyoma was shown to contain an abnormal collagen fibril structure and orientation, suggesting that the well-regulated fibril formation in myometrium is altered in leiomyomas.

• #72 Update on the Role and Regulatory Mechanism of Extracellular Matrix in the Pathogenesis of Uterine Fibroids

  https://www.mdpi.com/1422-0067/24/6/5778

  Numerous studies demonstrated that TGF-β signaling plays an important role in the pathogenesis of UFs. […] Abnormal ECM accumulation and deposition have been shown to be associated with the activation of TGF-β signaling in UFs. […] The ECM acts as a reservoir of profibrotic growth factors and enhances their activity by increasing their stability and prolonging signaling duration. […] The significant variations in the quantity and distribution of the ECM also create variation in the degree of UF tissue stiffness from soft to firm to solid to hard, with a major impact on the gene expression and biology of these tumor lesions. […] Pharmacological drugs can suppress the UF phenotype by inhibiting ECM production via multiple mechanisms, including epigenetics. […] However, several aspects need to be further elucidated, including characterizing the functional interaction of ECM-secreted cells with other types of cells, elucidating the impact of ECM on the microenvironment, and investigating the molecular and functional structure of ECM that regulates mechanotransduction and stiffness in both UFs and the at-risk MM.

• #73 Update on the Role and Regulatory Mechanism of Extracellular Matrix in the Pathogenesis of Uterine Fibroids

  https://www.mdpi.com/1422-0067/24/6/5778

  Numerous studies demonstrated that TGF-β signaling plays an important role in the pathogenesis of UFs. […] Abnormal ECM accumulation and deposition have been shown to be associated with the activation of TGF-β signaling in UFs. […] The ECM acts as a reservoir of profibrotic growth factors and enhances their activity by increasing their stability and prolonging signaling duration. […] The significant variations in the quantity and distribution of the ECM also create variation in the degree of UF tissue stiffness from soft to firm to solid to hard, with a major impact on the gene expression and biology of these tumor lesions. […] Pharmacological drugs can suppress the UF phenotype by inhibiting ECM production via multiple mechanisms, including epigenetics. […] However, several aspects need to be further elucidated, including characterizing the functional interaction of ECM-secreted cells with other types of cells, elucidating the impact of ECM on the microenvironment, and investigating the molecular and functional structure of ECM that regulates mechanotransduction and stiffness in both UFs and the at-risk MM.

• #74 Advanced 3D Imaging of Uterine Leiomyoma’s Morphology by Propagation-based Phase-Contrast Microtomography | Scientific Reports

  https://www.nature.com/articles/s41598-019-47048-0

  Thus, the study of specific collagen parameters, such as the size of collagen bundles, orientation and interconnectivity, turns out to be particularly interesting because its morphometry should determine specific cellular behaviors. […] The propagation-based phase-contrast microCT was used, for the first time to the authors knowledge, to evaluate the collagen amount and distribution in intramural fibroids excised from the uterus of two fertile women. […] In our study, we observed higher volumes, thickness and number of collagen bundles in the leiomyoma compared to normal adjacent myometrium. […] The presence of focal nodal collagen distribution in the myometrium, as in the case of uterine fibroids, could alter the normal uterine peristalsis through mechanical interference. […] The study from Yoshino and colleagues highlighted how myomectomy reduced the frequency of abnormal peristalsis in all patients. […] Therefore, the present and all these recent studies, provide novel evidences that structural properties of uterine leiomyoma and, even if less pronounced, also of the myometrium are widely heterogeneous.

• #75 Advanced 3D Imaging of Uterine Leiomyoma’s Morphology by Propagation-based Phase-Contrast Microtomography | Scientific Reports

  https://www.nature.com/articles/s41598-019-47048-0

  Thus, the study of specific collagen parameters, such as the size of collagen bundles, orientation and interconnectivity, turns out to be particularly interesting because its morphometry should determine specific cellular behaviors. […] The propagation-based phase-contrast microCT was used, for the first time to the authors knowledge, to evaluate the collagen amount and distribution in intramural fibroids excised from the uterus of two fertile women. […] In our study, we observed higher volumes, thickness and number of collagen bundles in the leiomyoma compared to normal adjacent myometrium. […] The presence of focal nodal collagen distribution in the myometrium, as in the case of uterine fibroids, could alter the normal uterine peristalsis through mechanical interference. […] The study from Yoshino and colleagues highlighted how myomectomy reduced the frequency of abnormal peristalsis in all patients. […] Therefore, the present and all these recent studies, provide novel evidences that structural properties of uterine leiomyoma and, even if less pronounced, also of the myometrium are widely heterogeneous.

• #76 Advanced 3D Imaging of Uterine Leiomyoma’s Morphology by Propagation-based Phase-Contrast Microtomography | Scientific Reports

  https://www.nature.com/articles/s41598-019-47048-0

  Thus, the study of specific collagen parameters, such as the size of collagen bundles, orientation and interconnectivity, turns out to be particularly interesting because its morphometry should determine specific cellular behaviors. […] The propagation-based phase-contrast microCT was used, for the first time to the authors knowledge, to evaluate the collagen amount and distribution in intramural fibroids excised from the uterus of two fertile women. […] In our study, we observed higher volumes, thickness and number of collagen bundles in the leiomyoma compared to normal adjacent myometrium. […] The presence of focal nodal collagen distribution in the myometrium, as in the case of uterine fibroids, could alter the normal uterine peristalsis through mechanical interference. […] The study from Yoshino and colleagues highlighted how myomectomy reduced the frequency of abnormal peristalsis in all patients. […] Therefore, the present and all these recent studies, provide novel evidences that structural properties of uterine leiomyoma and, even if less pronounced, also of the myometrium are widely heterogeneous.

• #77 Update on the Role and Regulatory Mechanism of Extracellular Matrix in the Pathogenesis of Uterine Fibroids

  https://www.mdpi.com/1422-0067/24/6/5778

  Numerous studies demonstrated that TGF-β signaling plays an important role in the pathogenesis of UFs. […] Abnormal ECM accumulation and deposition have been shown to be associated with the activation of TGF-β signaling in UFs. […] The ECM acts as a reservoir of profibrotic growth factors and enhances their activity by increasing their stability and prolonging signaling duration. […] The significant variations in the quantity and distribution of the ECM also create variation in the degree of UF tissue stiffness from soft to firm to solid to hard, with a major impact on the gene expression and biology of these tumor lesions. […] Pharmacological drugs can suppress the UF phenotype by inhibiting ECM production via multiple mechanisms, including epigenetics. […] However, several aspects need to be further elucidated, including characterizing the functional interaction of ECM-secreted cells with other types of cells, elucidating the impact of ECM on the microenvironment, and investigating the molecular and functional structure of ECM that regulates mechanotransduction and stiffness in both UFs and the at-risk MM.

• #78 New Insights into Molecular Pathogenesis of Uterine Fibroids: From the Lab to a Clinician-Friendly Review | IntechOpen

  https://www.intechopen.com/chapters/1165825

  Several studies have documented a pivotal role of inflammation and myofibroblastic transformation in the pathogenesis of UFs, and it is beginning to be accepted that local chronic inflammation generates a microenvironment that fosters the development of UFs. […] The consideration of UFs as a chronic inflammatory disease is supported by the presence of high expression of inflammatory cytokines in fibroids, including interleukin (IL)-1, IL-6, IL-13, IL-15, tumor necrosis factor (TNF)-, granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin. […] It has been proposed that a single myometrial stem cell goes through tumorigenic transformation following a cellular insult (genetic hit) and gives rise to daughter leiomyoma stem cell (TIC), which proliferate, undergo self-renewal, and clonally expand in response to steroid hormones via paracrine signaling from surrounding differentiated myometrial and leiomyoma cells.

• #79 Uterine Fibroids: The Science Behind Their Growth and Development

  https://www.linkedin.com/pulse/uterine-fibroids-science-behind-growth-development-bansal-nkc1f

  Emerging research suggests that the immune system may play a role in the pathogenesis of uterine fibroids. […] While genetic and hormonal factors are primary contributors to fibroid development, certain environmental and lifestyle factors can also influence the pathogenesis of uterine leiomyomas. […] The pathogenesis of uterine leiomyomas is multifaceted, involving genetic predisposition, hormonal influence, growth factors, ECM remodeling, vascular changes, immune system factors, and environmental/lifestyle factors.

• #80 New Insights into Molecular Pathogenesis of Uterine Fibroids: From the Lab to a Clinician-Friendly Review | IntechOpen

  https://www.intechopen.com/chapters/1165825

  Several studies have documented a pivotal role of inflammation and myofibroblastic transformation in the pathogenesis of UFs, and it is beginning to be accepted that local chronic inflammation generates a microenvironment that fosters the development of UFs. […] The consideration of UFs as a chronic inflammatory disease is supported by the presence of high expression of inflammatory cytokines in fibroids, including interleukin (IL)-1, IL-6, IL-13, IL-15, tumor necrosis factor (TNF)-, granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin. […] It has been proposed that a single myometrial stem cell goes through tumorigenic transformation following a cellular insult (genetic hit) and gives rise to daughter leiomyoma stem cell (TIC), which proliferate, undergo self-renewal, and clonally expand in response to steroid hormones via paracrine signaling from surrounding differentiated myometrial and leiomyoma cells.

• #81 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  Many cytokines, including tumor necrosis factor- , erythropoietin, interleukin- (IL-)1, and IL-6, have been implicated in development of uterine leiomyoma. […] Extracellular disorganized matrix is a peculiar characteristic of fibroid growth, mainly consisting of collagen subtypes, fibronectin, and proteoglycans. […] The etiopathology of uterine fibroid remains unclear, multifactorial, and enigmatic. […] Abnormal ECM expression, increased growth factors, cytokines and chemokines concentrations, and an extracellular disorganized matrix have been implicated in development and growth of uterine leiomyomas. […] Endomyometrial junction disruption might play a crucial role on fibroid-related infertility, uterine bleeding, and growth of submucosal and intramural myomas.

• #82

  https://journals.lww.com/md-journal/fulltext/2023/05190/search_for_key_genes,_key_signaling_pathways,_and.56.aspx

  In our study, using the CIBERSORT analysis tool, we analyzed the content and percentage of 22 immune cells in uterine fibroids. We found that the proportion of macrophage M1 in normal synovial tissue was higher. […] The results of bioinformatics analysis are helpful to further understand the pathogenesis of uterine fibroids.

• #83 New Insights into Molecular Pathogenesis of Uterine Fibroids: From the Lab to a Clinician-Friendly Review | IntechOpen

  https://www.intechopen.com/chapters/1165825

  Several studies have documented a pivotal role of inflammation and myofibroblastic transformation in the pathogenesis of UFs, and it is beginning to be accepted that local chronic inflammation generates a microenvironment that fosters the development of UFs. […] The consideration of UFs as a chronic inflammatory disease is supported by the presence of high expression of inflammatory cytokines in fibroids, including interleukin (IL)-1, IL-6, IL-13, IL-15, tumor necrosis factor (TNF)-, granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin. […] It has been proposed that a single myometrial stem cell goes through tumorigenic transformation following a cellular insult (genetic hit) and gives rise to daughter leiomyoma stem cell (TIC), which proliferate, undergo self-renewal, and clonally expand in response to steroid hormones via paracrine signaling from surrounding differentiated myometrial and leiomyoma cells.

• #84 New Insights into Molecular Pathogenesis of Uterine Fibroids: From the Lab to a Clinician-Friendly Review | IntechOpen

  https://www.intechopen.com/chapters/1165825

  Several studies have documented a pivotal role of inflammation and myofibroblastic transformation in the pathogenesis of UFs, and it is beginning to be accepted that local chronic inflammation generates a microenvironment that fosters the development of UFs. […] The consideration of UFs as a chronic inflammatory disease is supported by the presence of high expression of inflammatory cytokines in fibroids, including interleukin (IL)-1, IL-6, IL-13, IL-15, tumor necrosis factor (TNF)-, granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin. […] It has been proposed that a single myometrial stem cell goes through tumorigenic transformation following a cellular insult (genetic hit) and gives rise to daughter leiomyoma stem cell (TIC), which proliferate, undergo self-renewal, and clonally expand in response to steroid hormones via paracrine signaling from surrounding differentiated myometrial and leiomyoma cells.

• #85

  https://journals.lww.com/md-journal/fulltext/2023/05190/search_for_key_genes,_key_signaling_pathways,_and.56.aspx

  The formation of uterine fibroids is involved in the Wnt/-catenin signaling pathway, and the Wnt/-catenin signaling pathway also has a variety of physiological processes, such as tissue renewal, cell differentiation and proliferation. […] KEGG pathway analysis displayed that key genes were mainly enriched in Cytokine-cytokine receptor interaction, Focal adhesion, Ras signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, Fluid shear stress and atherosclerosis, Regulation of actin cytoskeleton, Rap1 signaling pathway, cAMP signaling pathway and Tight junction. […] Formation of uterine fibroids is associated with chronic inflammatory immune system. Chronic inflammatory immune characteristics can affect the occurrence and development of uterine fibroids because it will lead to an intensified immune system response in the female uterus, which will induce cell proliferation and fibrosis.

• #86

  https://journals.lww.com/md-journal/fulltext/2023/05190/search_for_key_genes,_key_signaling_pathways,_and.56.aspx

  The formation of uterine fibroids is involved in the Wnt/-catenin signaling pathway, and the Wnt/-catenin signaling pathway also has a variety of physiological processes, such as tissue renewal, cell differentiation and proliferation. […] KEGG pathway analysis displayed that key genes were mainly enriched in Cytokine-cytokine receptor interaction, Focal adhesion, Ras signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, Fluid shear stress and atherosclerosis, Regulation of actin cytoskeleton, Rap1 signaling pathway, cAMP signaling pathway and Tight junction. […] Formation of uterine fibroids is associated with chronic inflammatory immune system. Chronic inflammatory immune characteristics can affect the occurrence and development of uterine fibroids because it will lead to an intensified immune system response in the female uterus, which will induce cell proliferation and fibrosis.

• #87 Uterine fibroids: current perspectives | IJWH

  https://www.dovepress.com/uterine-fibroids-current-perspectives-peer-reviewed-fulltext-article-IJWH

  Uterine fibroids (also known as leiomyomas or myomas) are the commonest benign uterine tumors, with an estimated incidence of 20%40% in women during their reproductive years. They are monoclonal tumors of the uterine smooth muscle cells and consist of large amounts of extracellular matrix that contain collagen, fibronectin, and proteoglycan. Even though their pathogenesis is not clearly known, there is considerable evidence that estrogens and progestogens proliferate tumor growth, as the fibroids rarely appear before menarche and regress after menopause. […] The underlying biological mechanism of infection-related oncogenesis proposed is that injury caused by infection or inflammation proceeds through several possible pathways, leading to increased extracellular matrix, cell proliferation, and decreased apoptosis, apropos of abnormal tissue repair. The upregulation of extracellular matrix proteins that is consistently seen in gene profiling studies of fibroids compared with normal myometrium is consistent with such a mechanism.

• #88

  https://journals.lww.com/md-journal/fulltext/2023/05190/search_for_key_genes,_key_signaling_pathways,_and.56.aspx

  The formation of uterine fibroids is involved in the Wnt/-catenin signaling pathway, and the Wnt/-catenin signaling pathway also has a variety of physiological processes, such as tissue renewal, cell differentiation and proliferation. […] KEGG pathway analysis displayed that key genes were mainly enriched in Cytokine-cytokine receptor interaction, Focal adhesion, Ras signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, Fluid shear stress and atherosclerosis, Regulation of actin cytoskeleton, Rap1 signaling pathway, cAMP signaling pathway and Tight junction. […] Formation of uterine fibroids is associated with chronic inflammatory immune system. Chronic inflammatory immune characteristics can affect the occurrence and development of uterine fibroids because it will lead to an intensified immune system response in the female uterus, which will induce cell proliferation and fibrosis.

• #89 Uterine fibroids: current perspectives | IJWH

  https://www.dovepress.com/uterine-fibroids-current-perspectives-peer-reviewed-fulltext-article-IJWH

  Uterine fibroids (also known as leiomyomas or myomas) are the commonest benign uterine tumors, with an estimated incidence of 20%40% in women during their reproductive years. They are monoclonal tumors of the uterine smooth muscle cells and consist of large amounts of extracellular matrix that contain collagen, fibronectin, and proteoglycan. Even though their pathogenesis is not clearly known, there is considerable evidence that estrogens and progestogens proliferate tumor growth, as the fibroids rarely appear before menarche and regress after menopause. […] The underlying biological mechanism of infection-related oncogenesis proposed is that injury caused by infection or inflammation proceeds through several possible pathways, leading to increased extracellular matrix, cell proliferation, and decreased apoptosis, apropos of abnormal tissue repair. The upregulation of extracellular matrix proteins that is consistently seen in gene profiling studies of fibroids compared with normal myometrium is consistent with such a mechanism.

• #90 Vascular biology of uterine fibroids: connecting fibroids and vascular disorders in: Reproduction Volume 162 Issue 2 (2021)

  https://rep.bioscientifica.com/view/journals/rep/162/2/REP-21-0087.xml

  Fibroids are benign tumors caused by the proliferation of myometrial smooth muscle cells in the uterus that can lead to symptoms such as abdominal pain, constipation, urinary retention, and infertility. While traditionally thought of as a disease process intrinsic to the uterus, accumulating evidence suggests that fibroid growth may be linked with the systemic vasculature system, although cell-intrinsic factors are certainly of principal importance in their inception. Fibroids are associated with essential hypertension and preeclampsia, as well as atherosclerosis, for reasons that are becoming increasingly elucidated. Factors such as the reninangiotensinaldosterone system, estrogen, and endothelial dysfunction all likely play a role in fibroid pathogenesis. […] Despite the prevalence and burden of the disease, the origins and pathogenesis of fibroids remain largely a mystery. Clues to possible driving factors for the development and propagation of fibroids have come from their risk factors. Epidemiological studies have demonstrated that genetic factors such as positive family history and hypertension portend an increased risk of fibroids, suggesting that these factors may influence vascular dysfunction and play a role in fibroid pathogenesis.

• #91 Why do fibroids in the uterus cause severe bleeding?

  https://chennaigynecologist.com/why-do-fibroids-in-the-uterus-cause-severe-bleeding/

  The most common condition underlying severe bleeding are uterine fibroids. […] Severe bleeding is a common symptom of uterine fibroids. Heavy bleeding due to uterine fibroids has been shown to correlate with the position and number of fibroids. […] Type and location of fibroid can cause severe bleeding – Uterine fibroids are classified according to their location relative to the uterine anatomy in the FIGO system. […] Physical mechanism can make fibroids cause severe bleeding – Fibroids may cause heavy bleeding through an increase in endometrial surface due to underlying fibroid growth. […] Angiogenesis in fibroids can cause severe bleeding – There is no other tissue in the human body that undergoes angiogenesis to the degree and frequency as the endometrium. […] Pseudocapsule in fibroids could explain severe bleeding – The fibroid mass is poorly vascularised but it can be surrounded by a pseudocapsule which is a highly vascularised tissue that develops only in intramural fibroids.

• #92 Vascular biology of uterine fibroids: connecting fibroids and vascular disorders in: Reproduction Volume 162 Issue 2 (2021)

  https://rep.bioscientifica.com/view/journals/rep/162/2/REP-21-0087.xml

  The consistent evidence of the correlation between hypertension and uterine fibroids raises the prospect, once again, of vascular involvement in fibroid pathobiology. […] The hypovascularity of fibroids creates a hypoxic microenvironment that serves as a positive feedback loop driving proliferation and neovascularization. For instance, endothelin-1 (ET-1) is a potent vasoconstrictor peptide secreted by endothelial cells and fibroid smooth muscle cells in response to hypoxia. ET-1 is elevated in the plasma of women with fibroids, compared to those without, and drives fibroid cell proliferation. […] Aberrant activation of the RAA system is implicated in fibroid cell proliferation through the actions of Ang-II and aldosterone. […] Collectively, increased cellular proliferation, decreased apoptosis and enhanced ECM synthesis promote fibroid growth.

• #93

  https://www.archivesofmedicalscience.com/Identification-of-PDGFR-cells-in-uterine-fibroids-link-between-angiogenesis-and-uterine,110052,0,2.html

  The decline of the telocyte density in the foci of fibroids correlated with poor vascularization inside the leiomyoma. […] Our results demonstrate TCs in human uterine fibroids and highlight their possible involvement in the pathogenesis of myometrial pathology in the context of angiogenesis. […] Uterine leiomyoma is strongly associated with local hypoxia, which in turn stimulated production of extracellular matrix as well as an angiogenic response in the myometrial tissue. […] Hypoxia stimulates production of soluble fms-like tyrosine kinase 1 (sFlt-1) or VEGFR-1 (VEGF receptor-1), an anti-angiogenic-related factor. […] We suggest that the interplay of TCs and adjacent cells could reveal new aspects in the pathophysiology of myometrial changes. […] We revealed the presence of TCs in uterine fibroids.

• #94 Vascular biology of uterine fibroids: connecting fibroids and vascular disorders in: Reproduction Volume 162 Issue 2 (2021)

  https://rep.bioscientifica.com/view/journals/rep/162/2/REP-21-0087.xml

  The consistent evidence of the correlation between hypertension and uterine fibroids raises the prospect, once again, of vascular involvement in fibroid pathobiology. […] The hypovascularity of fibroids creates a hypoxic microenvironment that serves as a positive feedback loop driving proliferation and neovascularization. For instance, endothelin-1 (ET-1) is a potent vasoconstrictor peptide secreted by endothelial cells and fibroid smooth muscle cells in response to hypoxia. ET-1 is elevated in the plasma of women with fibroids, compared to those without, and drives fibroid cell proliferation. […] Aberrant activation of the RAA system is implicated in fibroid cell proliferation through the actions of Ang-II and aldosterone. […] Collectively, increased cellular proliferation, decreased apoptosis and enhanced ECM synthesis promote fibroid growth.

• #95 Why do fibroids in the uterus cause severe bleeding?

  https://chennaigynecologist.com/why-do-fibroids-in-the-uterus-cause-severe-bleeding/

  Venous lakes in fibroids can be responsible for increased bleeding – Severe bleeding connected to uterine fibroids suggests physiological formation of venous lakes which are large sinusoidal structures within the uterine vasculature from arteriovenous anastomoses. […] Aberrant architecture of fibroid can cause severe bleeding – The vasculature developing around uterine fibroids could show structural defects that could be highly irregular, with high tortuosity, shunting of vessels and non-patent ends.

• #96 Why do fibroids in the uterus cause severe bleeding?

  https://chennaigynecologist.com/why-do-fibroids-in-the-uterus-cause-severe-bleeding/

  Venous lakes in fibroids can be responsible for increased bleeding – Severe bleeding connected to uterine fibroids suggests physiological formation of venous lakes which are large sinusoidal structures within the uterine vasculature from arteriovenous anastomoses. […] Aberrant architecture of fibroid can cause severe bleeding – The vasculature developing around uterine fibroids could show structural defects that could be highly irregular, with high tortuosity, shunting of vessels and non-patent ends.

• #97 Why do fibroids in the uterus cause severe bleeding?

  https://chennaigynecologist.com/why-do-fibroids-in-the-uterus-cause-severe-bleeding/

  The most common condition underlying severe bleeding are uterine fibroids. […] Severe bleeding is a common symptom of uterine fibroids. Heavy bleeding due to uterine fibroids has been shown to correlate with the position and number of fibroids. […] Type and location of fibroid can cause severe bleeding – Uterine fibroids are classified according to their location relative to the uterine anatomy in the FIGO system. […] Physical mechanism can make fibroids cause severe bleeding – Fibroids may cause heavy bleeding through an increase in endometrial surface due to underlying fibroid growth. […] Angiogenesis in fibroids can cause severe bleeding – There is no other tissue in the human body that undergoes angiogenesis to the degree and frequency as the endometrium. […] Pseudocapsule in fibroids could explain severe bleeding – The fibroid mass is poorly vascularised but it can be surrounded by a pseudocapsule which is a highly vascularised tissue that develops only in intramural fibroids.

• #98 Vascular biology of uterine fibroids: connecting fibroids and vascular disorders in: Reproduction Volume 162 Issue 2 (2021)

  https://rep.bioscientifica.com/view/journals/rep/162/2/REP-21-0087.xml

  The consistent evidence of the correlation between hypertension and uterine fibroids raises the prospect, once again, of vascular involvement in fibroid pathobiology. […] The hypovascularity of fibroids creates a hypoxic microenvironment that serves as a positive feedback loop driving proliferation and neovascularization. For instance, endothelin-1 (ET-1) is a potent vasoconstrictor peptide secreted by endothelial cells and fibroid smooth muscle cells in response to hypoxia. ET-1 is elevated in the plasma of women with fibroids, compared to those without, and drives fibroid cell proliferation. […] Aberrant activation of the RAA system is implicated in fibroid cell proliferation through the actions of Ang-II and aldosterone. […] Collectively, increased cellular proliferation, decreased apoptosis and enhanced ECM synthesis promote fibroid growth.

• #99 Why do fibroids in the uterus cause severe bleeding?

  https://chennaigynecologist.com/why-do-fibroids-in-the-uterus-cause-severe-bleeding/

  Venous lakes in fibroids can be responsible for increased bleeding – Severe bleeding connected to uterine fibroids suggests physiological formation of venous lakes which are large sinusoidal structures within the uterine vasculature from arteriovenous anastomoses. […] Aberrant architecture of fibroid can cause severe bleeding – The vasculature developing around uterine fibroids could show structural defects that could be highly irregular, with high tortuosity, shunting of vessels and non-patent ends.

• #100 Vascular biology of uterine fibroids: connecting fibroids and vascular disorders in: Reproduction Volume 162 Issue 2 (2021)

  https://rep.bioscientifica.com/view/journals/rep/162/2/REP-21-0087.xml

  Fibroids are benign tumors caused by the proliferation of myometrial smooth muscle cells in the uterus that can lead to symptoms such as abdominal pain, constipation, urinary retention, and infertility. While traditionally thought of as a disease process intrinsic to the uterus, accumulating evidence suggests that fibroid growth may be linked with the systemic vasculature system, although cell-intrinsic factors are certainly of principal importance in their inception. Fibroids are associated with essential hypertension and preeclampsia, as well as atherosclerosis, for reasons that are becoming increasingly elucidated. Factors such as the reninangiotensinaldosterone system, estrogen, and endothelial dysfunction all likely play a role in fibroid pathogenesis. […] Despite the prevalence and burden of the disease, the origins and pathogenesis of fibroids remain largely a mystery. Clues to possible driving factors for the development and propagation of fibroids have come from their risk factors. Epidemiological studies have demonstrated that genetic factors such as positive family history and hypertension portend an increased risk of fibroids, suggesting that these factors may influence vascular dysfunction and play a role in fibroid pathogenesis.

• #101 Vascular biology of uterine fibroids: connecting fibroids and vascular disorders in: Reproduction Volume 162 Issue 2 (2021)

  https://rep.bioscientifica.com/view/journals/rep/162/2/REP-21-0087.xml

  The association between uterine fibroids and hypertension has been extensively addressed in the literature. Several studies have found a significant positive correlation between the two disorders, but causality has not yet been successfully established. […] An accumulating body of evidence has supported the notion that uterine fibroids and atherosclerosis bear pathophysiological resemblance. This hypothesis is reinforced by several observations: (1) both atherosclerosis and uterine fibroids represent a pathological proliferative lesion of smooth muscle cells; (2) similar to fibroids, atheromatous plaques may have a monoclonal origin; and (3) both lesions can eventually fibrose and calcify. […] Elevated blood pressure also induces proinflammatory milieus and upregulates ECM synthesis, in part through the action of TGF-, which has been seen to activate fibroblasts in rats induced to have hypertension.

• #102 Vascular biology of uterine fibroids: connecting fibroids and vascular disorders in: Reproduction Volume 162 Issue 2 (2021)

  https://rep.bioscientifica.com/view/journals/rep/162/2/REP-21-0087.xml

  The association between uterine fibroids and hypertension has been extensively addressed in the literature. Several studies have found a significant positive correlation between the two disorders, but causality has not yet been successfully established. […] An accumulating body of evidence has supported the notion that uterine fibroids and atherosclerosis bear pathophysiological resemblance. This hypothesis is reinforced by several observations: (1) both atherosclerosis and uterine fibroids represent a pathological proliferative lesion of smooth muscle cells; (2) similar to fibroids, atheromatous plaques may have a monoclonal origin; and (3) both lesions can eventually fibrose and calcify. […] Elevated blood pressure also induces proinflammatory milieus and upregulates ECM synthesis, in part through the action of TGF-, which has been seen to activate fibroblasts in rats induced to have hypertension.

• #103

  https://www.archivesofmedicalscience.com/Identification-of-PDGFR-cells-in-uterine-fibroids-link-between-angiogenesis-and-uterine,110052,0,2.html

  The decline of the telocyte density in the foci of fibroids correlated with poor vascularization inside the leiomyoma. […] Our results demonstrate TCs in human uterine fibroids and highlight their possible involvement in the pathogenesis of myometrial pathology in the context of angiogenesis. […] Uterine leiomyoma is strongly associated with local hypoxia, which in turn stimulated production of extracellular matrix as well as an angiogenic response in the myometrial tissue. […] Hypoxia stimulates production of soluble fms-like tyrosine kinase 1 (sFlt-1) or VEGFR-1 (VEGF receptor-1), an anti-angiogenic-related factor. […] We suggest that the interplay of TCs and adjacent cells could reveal new aspects in the pathophysiology of myometrial changes. […] We revealed the presence of TCs in uterine fibroids.

• #104 Role of Senescent Cells in Uterine Fibroid Pathogenesis (SOUL Study) | Clinical Research Trial Listing

  https://www.centerwatch.com/clinical-trials/listings/NCT06135870/role-of-senescent-cells-in-uterine-fibroid-pathogenesis-soul-study

  The investigators are evaluating the role of senescent cells in uterine fibroids. […] Using new cutting-edge computational methods, the investigators have found that small groups of senescent cells in fibroids work in concert with immune cells to produce soluble factors in fibroid tissues to create a feed-forward loop leading to fibrosis. […] This project seeks to unravel key cell-cell communication networks involving senescent and immune cells in fibroids to develop new treatments for uterine fibroids.

• #105

  https://www.archivesofmedicalscience.com/Identification-of-PDGFR-cells-in-uterine-fibroids-link-between-angiogenesis-and-uterine,110052,0,2.html

  We intend to provide further quantitative analysis of TC number in the foci of myoma and healthy myometrium, although we could hypothesize that the density of TCs declines in leiomyoma. […] We observed a decrease of vascularization in the foci of leiomyoma, accompanied by increasing expression of VEGF receptor-1 (sFlt-1). […] Uterine telocytes are sensitive to angiogenic factors (PDGF and VEGF) and ischemia; they declined and even disappeared during fibrosis, observed in close vicinity to blood vessels. […] We hypothesize that in-depth observation of TCs in the human uterus brings additional value to reproductive medicine.

• #106

  https://www.archivesofmedicalscience.com/Identification-of-PDGFR-cells-in-uterine-fibroids-link-between-angiogenesis-and-uterine,110052,0,2.html

  The decline of the telocyte density in the foci of fibroids correlated with poor vascularization inside the leiomyoma. […] Our results demonstrate TCs in human uterine fibroids and highlight their possible involvement in the pathogenesis of myometrial pathology in the context of angiogenesis. […] Uterine leiomyoma is strongly associated with local hypoxia, which in turn stimulated production of extracellular matrix as well as an angiogenic response in the myometrial tissue. […] Hypoxia stimulates production of soluble fms-like tyrosine kinase 1 (sFlt-1) or VEGFR-1 (VEGF receptor-1), an anti-angiogenic-related factor. […] We suggest that the interplay of TCs and adjacent cells could reveal new aspects in the pathophysiology of myometrial changes. […] We revealed the presence of TCs in uterine fibroids.

• #107 Role of Senescent Cells in Uterine Fibroid Pathogenesis (SOUL Study) | Clinical Research Trial Listing

  https://www.centerwatch.com/clinical-trials/listings/NCT06135870/role-of-senescent-cells-in-uterine-fibroid-pathogenesis-soul-study

  The investigators are evaluating the role of senescent cells in uterine fibroids. […] Using new cutting-edge computational methods, the investigators have found that small groups of senescent cells in fibroids work in concert with immune cells to produce soluble factors in fibroid tissues to create a feed-forward loop leading to fibrosis. […] This project seeks to unravel key cell-cell communication networks involving senescent and immune cells in fibroids to develop new treatments for uterine fibroids.

• #108 Lake Clinical Trial Role of Senescent Cells in Uterine Fibroid Pathogenesis (SOUL Study)

  https://mentalhealth.networkofcare.org/Lake/CommunityResources/ClinicalTrials/Detail/NCT06135870?keyword=%22Fibroid%22

  Uterine fibroids are prevalent tumors of uterus characterized by excessive fibrotic tissues. Using new cutting-edge computational methods, the investigators have found that small groups of senescent cells in fibroids work in concert with immune cells to produce soluble factors in fibroid tissues to create a feed-forward loop leading to fibrosis. This project seeks to unravel key cell-cell communication networks involving senescent and immune cells in fibroids to develop new treatments for uterine fibroids.

• #109

  https://www.archivesofmedicalscience.com/Identification-of-PDGFR-cells-in-uterine-fibroids-link-between-angiogenesis-and-uterine,110052,0,2.html

  We intend to provide further quantitative analysis of TC number in the foci of myoma and healthy myometrium, although we could hypothesize that the density of TCs declines in leiomyoma. […] We observed a decrease of vascularization in the foci of leiomyoma, accompanied by increasing expression of VEGF receptor-1 (sFlt-1). […] Uterine telocytes are sensitive to angiogenic factors (PDGF and VEGF) and ischemia; they declined and even disappeared during fibrosis, observed in close vicinity to blood vessels. […] We hypothesize that in-depth observation of TCs in the human uterus brings additional value to reproductive medicine.

• #110 Lake Clinical Trial Role of Senescent Cells in Uterine Fibroid Pathogenesis (SOUL Study)

  https://mentalhealth.networkofcare.org/Lake/CommunityResources/ClinicalTrials/Detail/NCT06135870?keyword=%22Fibroid%22

  Uterine fibroids are prevalent tumors of uterus characterized by excessive fibrotic tissues. Using new cutting-edge computational methods, the investigators have found that small groups of senescent cells in fibroids work in concert with immune cells to produce soluble factors in fibroid tissues to create a feed-forward loop leading to fibrosis. This project seeks to unravel key cell-cell communication networks involving senescent and immune cells in fibroids to develop new treatments for uterine fibroids.

• #111 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  The adipose tissue converts adrenal and ovarian androgens into estrogens, whereas several mechanisms associated with obesity lead to decreased synthesis of sex hormone binding globulin. […] Several studies have revealed that smoking may reduce the incidence of myomas; nicotine inhibits aromatase and reduces the conversion of androgens to estrone. […] An early menarche, before the age of 10, has been found to be a risk factor for uterine myomas, while a menarche over the age of 16 seems to decrease the same risk. […] The HMGA2 gene was found in translocation 12:14, the most common cytogenetic abnormality, that occurs in about 20% of chromosomally abnormal lesions. […] Recent studies described that 70% of fibroids contained a series of mutations in a transcriptional regulator complex subunit 12 (MED12).

• #112 A COMPREHENSIVE REVIEW OF UTERINE FIBROIDS: PATHOGENESIS, DIAGNOSIS, TREATMENT, AND FUTURE PERSPECTIVES | Journal of Population Therapeutics and Clinical Pharmacology

  https://www.jptcp.com/index.php/jptcp/article/view/3385

  Fibroid, myoma, and leiomyoma are interchangeable terms used to describe the most common gynecological tumors, which are benign neoplasms originating in the smooth muscles of the uterus. […] Age and race are the primary risk factors for uterine fibroids, with African American women experiencing higher incidence rates compared to Caucasian women. […] A family history of uterine fibroids also increases the risk of developing them. […] Lifestyle factors such as obesity, dietary choices, sedentary living, and smoking have been linked to fibroid occurrence, possibly due to their influence on estrogen production. […] Stress may also be a contributing risk factor for fibroids, as it is associated with a higher body mass index. […] A diet rich in red meat has been connected to a 70% increased risk of fibroids. […] It’s worth noting that large fibroids can impact the uterine cavity’s configuration, potentially affecting embryo implantation and increasing the risk of miscarriage.

• #113 A COMPREHENSIVE REVIEW OF UTERINE FIBROIDS: PATHOGENESIS, DIAGNOSIS, TREATMENT, AND FUTURE PERSPECTIVES | Journal of Population Therapeutics and Clinical Pharmacology

  https://www.jptcp.com/index.php/jptcp/article/view/3385

  Fibroid, myoma, and leiomyoma are interchangeable terms used to describe the most common gynecological tumors, which are benign neoplasms originating in the smooth muscles of the uterus. […] Age and race are the primary risk factors for uterine fibroids, with African American women experiencing higher incidence rates compared to Caucasian women. […] A family history of uterine fibroids also increases the risk of developing them. […] Lifestyle factors such as obesity, dietary choices, sedentary living, and smoking have been linked to fibroid occurrence, possibly due to their influence on estrogen production. […] Stress may also be a contributing risk factor for fibroids, as it is associated with a higher body mass index. […] A diet rich in red meat has been connected to a 70% increased risk of fibroids. […] It’s worth noting that large fibroids can impact the uterine cavity’s configuration, potentially affecting embryo implantation and increasing the risk of miscarriage.

• #114 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  The adipose tissue converts adrenal and ovarian androgens into estrogens, whereas several mechanisms associated with obesity lead to decreased synthesis of sex hormone binding globulin. […] Several studies have revealed that smoking may reduce the incidence of myomas; nicotine inhibits aromatase and reduces the conversion of androgens to estrone. […] An early menarche, before the age of 10, has been found to be a risk factor for uterine myomas, while a menarche over the age of 16 seems to decrease the same risk. […] The HMGA2 gene was found in translocation 12:14, the most common cytogenetic abnormality, that occurs in about 20% of chromosomally abnormal lesions. […] Recent studies described that 70% of fibroids contained a series of mutations in a transcriptional regulator complex subunit 12 (MED12).

• #115 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  The adipose tissue converts adrenal and ovarian androgens into estrogens, whereas several mechanisms associated with obesity lead to decreased synthesis of sex hormone binding globulin. […] Several studies have revealed that smoking may reduce the incidence of myomas; nicotine inhibits aromatase and reduces the conversion of androgens to estrone. […] An early menarche, before the age of 10, has been found to be a risk factor for uterine myomas, while a menarche over the age of 16 seems to decrease the same risk. […] The HMGA2 gene was found in translocation 12:14, the most common cytogenetic abnormality, that occurs in about 20% of chromosomally abnormal lesions. […] Recent studies described that 70% of fibroids contained a series of mutations in a transcriptional regulator complex subunit 12 (MED12).

• #116 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  The adipose tissue converts adrenal and ovarian androgens into estrogens, whereas several mechanisms associated with obesity lead to decreased synthesis of sex hormone binding globulin. […] Several studies have revealed that smoking may reduce the incidence of myomas; nicotine inhibits aromatase and reduces the conversion of androgens to estrone. […] An early menarche, before the age of 10, has been found to be a risk factor for uterine myomas, while a menarche over the age of 16 seems to decrease the same risk. […] The HMGA2 gene was found in translocation 12:14, the most common cytogenetic abnormality, that occurs in about 20% of chromosomally abnormal lesions. […] Recent studies described that 70% of fibroids contained a series of mutations in a transcriptional regulator complex subunit 12 (MED12).

• #117 A COMPREHENSIVE REVIEW OF UTERINE FIBROIDS: PATHOGENESIS, DIAGNOSIS, TREATMENT, AND FUTURE PERSPECTIVES | Journal of Population Therapeutics and Clinical Pharmacology

  https://www.jptcp.com/index.php/jptcp/article/view/3385

  Fibroid, myoma, and leiomyoma are interchangeable terms used to describe the most common gynecological tumors, which are benign neoplasms originating in the smooth muscles of the uterus. […] Age and race are the primary risk factors for uterine fibroids, with African American women experiencing higher incidence rates compared to Caucasian women. […] A family history of uterine fibroids also increases the risk of developing them. […] Lifestyle factors such as obesity, dietary choices, sedentary living, and smoking have been linked to fibroid occurrence, possibly due to their influence on estrogen production. […] Stress may also be a contributing risk factor for fibroids, as it is associated with a higher body mass index. […] A diet rich in red meat has been connected to a 70% increased risk of fibroids. […] It’s worth noting that large fibroids can impact the uterine cavity’s configuration, potentially affecting embryo implantation and increasing the risk of miscarriage.

• #118 Vascular biology of uterine fibroids: connecting fibroids and vascular disorders in: Reproduction Volume 162 Issue 2 (2021)

  https://rep.bioscientifica.com/view/journals/rep/162/2/REP-21-0087.xml

  Fibroids are benign tumors caused by the proliferation of myometrial smooth muscle cells in the uterus that can lead to symptoms such as abdominal pain, constipation, urinary retention, and infertility. While traditionally thought of as a disease process intrinsic to the uterus, accumulating evidence suggests that fibroid growth may be linked with the systemic vasculature system, although cell-intrinsic factors are certainly of principal importance in their inception. Fibroids are associated with essential hypertension and preeclampsia, as well as atherosclerosis, for reasons that are becoming increasingly elucidated. Factors such as the reninangiotensinaldosterone system, estrogen, and endothelial dysfunction all likely play a role in fibroid pathogenesis. […] Despite the prevalence and burden of the disease, the origins and pathogenesis of fibroids remain largely a mystery. Clues to possible driving factors for the development and propagation of fibroids have come from their risk factors. Epidemiological studies have demonstrated that genetic factors such as positive family history and hypertension portend an increased risk of fibroids, suggesting that these factors may influence vascular dysfunction and play a role in fibroid pathogenesis.

• #119 Endocrine-Disrupting Chemicals and Vitamin D Deficiency in the Pathogenesis of Uterine Fibroids

  https://aprh.journals.ekb.eg/article_166066.html

  Uterine fibroids (UFs) are the most prevalent gynecologic neoplasm, affecting 70-80% of women over their lifespan. […] Notwithstanding the significant negative influence, UFs have on female reproductive health, very little is known about early events that initiate tumor development. […] Several risk factors for UFs have been identified, including vitamin D deficiency, inflammation, DNA repair deficiency, and environmental exposures to endocrine-disrupting chemicals (EDCs). […] EDCs have come under scrutiny recently due to their role in UF development. […] Environmental exposure to EDCs during uterine development increases UF incidence in a UF animal model. […] Notably, several studies demonstrated that abnormal myometrial stem cells (MMSCs) are the cell origin for UFs development.

• #120 Endocrine-Disrupting Chemicals and Vitamin D Deficiency in the Pathogenesis of Uterine Fibroids

  https://aprh.journals.ekb.eg/article_166066.html

  Our recent studies demonstrated that early-life EDC exposure reprogrammed the MMSCs toward a pro-fibroid landscape and altered the DNA repair and inflammation pathways. […] Notably, Vitamin D3 (VITD3) as a natural compound shrank the UF growth concomitantly with the reversion of several abnormal biological pathways. […] It ameliorated the developmental exposure-induced DNA damage and pro-inflammation pathway in primed MMSCs. […] This review highlights and emphasizes the importance of multiple pathway interactions in the context of hypovitaminosis D at the MMSCs level and provides proof-of-concept information that can help develop a safe, long-term, durable, and non-surgical therapeutic option for UFs.

• #121 Endocrine-Disrupting Chemicals and Vitamin D Deficiency in the Pathogenesis of Uterine Fibroids

  https://aprh.journals.ekb.eg/article_166066.html

  Uterine fibroids (UFs) are the most prevalent gynecologic neoplasm, affecting 70-80% of women over their lifespan. […] Notwithstanding the significant negative influence, UFs have on female reproductive health, very little is known about early events that initiate tumor development. […] Several risk factors for UFs have been identified, including vitamin D deficiency, inflammation, DNA repair deficiency, and environmental exposures to endocrine-disrupting chemicals (EDCs). […] EDCs have come under scrutiny recently due to their role in UF development. […] Environmental exposure to EDCs during uterine development increases UF incidence in a UF animal model. […] Notably, several studies demonstrated that abnormal myometrial stem cells (MMSCs) are the cell origin for UFs development.

• #122 Endocrine-Disrupting Chemicals and Vitamin D Deficiency in the Pathogenesis of Uterine Fibroids

  https://aprh.journals.ekb.eg/article_166066.html

  Our recent studies demonstrated that early-life EDC exposure reprogrammed the MMSCs toward a pro-fibroid landscape and altered the DNA repair and inflammation pathways. […] Notably, Vitamin D3 (VITD3) as a natural compound shrank the UF growth concomitantly with the reversion of several abnormal biological pathways. […] It ameliorated the developmental exposure-induced DNA damage and pro-inflammation pathway in primed MMSCs. […] This review highlights and emphasizes the importance of multiple pathway interactions in the context of hypovitaminosis D at the MMSCs level and provides proof-of-concept information that can help develop a safe, long-term, durable, and non-surgical therapeutic option for UFs.

• #123 A COMPREHENSIVE REVIEW OF UTERINE FIBROIDS: PATHOGENESIS, DIAGNOSIS, TREATMENT, AND FUTURE PERSPECTIVES | Journal of Population Therapeutics and Clinical Pharmacology

  https://www.jptcp.com/index.php/jptcp/article/view/3385

  Fibroid, myoma, and leiomyoma are interchangeable terms used to describe the most common gynecological tumors, which are benign neoplasms originating in the smooth muscles of the uterus. […] Age and race are the primary risk factors for uterine fibroids, with African American women experiencing higher incidence rates compared to Caucasian women. […] A family history of uterine fibroids also increases the risk of developing them. […] Lifestyle factors such as obesity, dietary choices, sedentary living, and smoking have been linked to fibroid occurrence, possibly due to their influence on estrogen production. […] Stress may also be a contributing risk factor for fibroids, as it is associated with a higher body mass index. […] A diet rich in red meat has been connected to a 70% increased risk of fibroids. […] It’s worth noting that large fibroids can impact the uterine cavity’s configuration, potentially affecting embryo implantation and increasing the risk of miscarriage.

• #124 A COMPREHENSIVE REVIEW OF UTERINE FIBROIDS: PATHOGENESIS, DIAGNOSIS, TREATMENT, AND FUTURE PERSPECTIVES | Journal of Population Therapeutics and Clinical Pharmacology

  https://www.jptcp.com/index.php/jptcp/article/view/3385

  Fibroid, myoma, and leiomyoma are interchangeable terms used to describe the most common gynecological tumors, which are benign neoplasms originating in the smooth muscles of the uterus. […] Age and race are the primary risk factors for uterine fibroids, with African American women experiencing higher incidence rates compared to Caucasian women. […] A family history of uterine fibroids also increases the risk of developing them. […] Lifestyle factors such as obesity, dietary choices, sedentary living, and smoking have been linked to fibroid occurrence, possibly due to their influence on estrogen production. […] Stress may also be a contributing risk factor for fibroids, as it is associated with a higher body mass index. […] A diet rich in red meat has been connected to a 70% increased risk of fibroids. […] It’s worth noting that large fibroids can impact the uterine cavity’s configuration, potentially affecting embryo implantation and increasing the risk of miscarriage.

• #125 A COMPREHENSIVE REVIEW OF UTERINE FIBROIDS: PATHOGENESIS, DIAGNOSIS, TREATMENT, AND FUTURE PERSPECTIVES | Journal of Population Therapeutics and Clinical Pharmacology

  https://www.jptcp.com/index.php/jptcp/article/view/3385

  Fibroid, myoma, and leiomyoma are interchangeable terms used to describe the most common gynecological tumors, which are benign neoplasms originating in the smooth muscles of the uterus. […] Age and race are the primary risk factors for uterine fibroids, with African American women experiencing higher incidence rates compared to Caucasian women. […] A family history of uterine fibroids also increases the risk of developing them. […] Lifestyle factors such as obesity, dietary choices, sedentary living, and smoking have been linked to fibroid occurrence, possibly due to their influence on estrogen production. […] Stress may also be a contributing risk factor for fibroids, as it is associated with a higher body mass index. […] A diet rich in red meat has been connected to a 70% increased risk of fibroids. […] It’s worth noting that large fibroids can impact the uterine cavity’s configuration, potentially affecting embryo implantation and increasing the risk of miscarriage.

• #126 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  The adipose tissue converts adrenal and ovarian androgens into estrogens, whereas several mechanisms associated with obesity lead to decreased synthesis of sex hormone binding globulin. […] Several studies have revealed that smoking may reduce the incidence of myomas; nicotine inhibits aromatase and reduces the conversion of androgens to estrone. […] An early menarche, before the age of 10, has been found to be a risk factor for uterine myomas, while a menarche over the age of 16 seems to decrease the same risk. […] The HMGA2 gene was found in translocation 12:14, the most common cytogenetic abnormality, that occurs in about 20% of chromosomally abnormal lesions. […] Recent studies described that 70% of fibroids contained a series of mutations in a transcriptional regulator complex subunit 12 (MED12).

• #127 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  The adipose tissue converts adrenal and ovarian androgens into estrogens, whereas several mechanisms associated with obesity lead to decreased synthesis of sex hormone binding globulin. […] Several studies have revealed that smoking may reduce the incidence of myomas; nicotine inhibits aromatase and reduces the conversion of androgens to estrone. […] An early menarche, before the age of 10, has been found to be a risk factor for uterine myomas, while a menarche over the age of 16 seems to decrease the same risk. […] The HMGA2 gene was found in translocation 12:14, the most common cytogenetic abnormality, that occurs in about 20% of chromosomally abnormal lesions. […] Recent studies described that 70% of fibroids contained a series of mutations in a transcriptional regulator complex subunit 12 (MED12).

• #128 New Insights into Molecular Pathogenesis of Uterine Fibroids: From the Lab to a Clinician-Friendly Review | IntechOpen

  https://www.intechopen.com/chapters/1165825

  In recent years, many advances have been made, allowing us to understand the molecular mechanisms underlying the pathogenesis of UFs. […] It has been hypothesized that uterine hypoxia, aberrant methylation, or abnormal estrogen signaling could play a critical role in the transformation of a myometrial stem cell into a TIC. […] It has been demonstrated that paracrine activation of the wingless-type (Wnt)/-catenin pathway mediated by estrogen and progesterone has a critical role in enhancing the growth and proliferation of leiomyoma stem cells. […] The presence of steroid hormones stimulates the secretion of Wnt ligands from mature myometrium or leiomyoma cells. […] The development of clinical disease is dependent on a paracrine mechanism and a multistep process from transformation to the fibroid progenitor through to growth acceleration.

• #129 New Insights into Molecular Pathogenesis of Uterine Fibroids: From the Lab to a Clinician-Friendly Review | IntechOpen

  https://www.intechopen.com/chapters/1165825

  Several studies have documented a pivotal role of inflammation and myofibroblastic transformation in the pathogenesis of UFs, and it is beginning to be accepted that local chronic inflammation generates a microenvironment that fosters the development of UFs. […] The consideration of UFs as a chronic inflammatory disease is supported by the presence of high expression of inflammatory cytokines in fibroids, including interleukin (IL)-1, IL-6, IL-13, IL-15, tumor necrosis factor (TNF)-, granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin. […] It has been proposed that a single myometrial stem cell goes through tumorigenic transformation following a cellular insult (genetic hit) and gives rise to daughter leiomyoma stem cell (TIC), which proliferate, undergo self-renewal, and clonally expand in response to steroid hormones via paracrine signaling from surrounding differentiated myometrial and leiomyoma cells.

• #130 New Insights into Molecular Pathogenesis of Uterine Fibroids: From the Lab to a Clinician-Friendly Review | IntechOpen

  https://www.intechopen.com/chapters/1165825

  In recent years, many advances have been made, allowing us to understand the molecular mechanisms underlying the pathogenesis of UFs. […] It has been hypothesized that uterine hypoxia, aberrant methylation, or abnormal estrogen signaling could play a critical role in the transformation of a myometrial stem cell into a TIC. […] It has been demonstrated that paracrine activation of the wingless-type (Wnt)/-catenin pathway mediated by estrogen and progesterone has a critical role in enhancing the growth and proliferation of leiomyoma stem cells. […] The presence of steroid hormones stimulates the secretion of Wnt ligands from mature myometrium or leiomyoma cells. […] The development of clinical disease is dependent on a paracrine mechanism and a multistep process from transformation to the fibroid progenitor through to growth acceleration.

• #131 New Insights into Molecular Pathogenesis of Uterine Fibroids: From the Lab to a Clinician-Friendly Review | IntechOpen

  https://www.intechopen.com/chapters/1165825

  Several studies have documented a pivotal role of inflammation and myofibroblastic transformation in the pathogenesis of UFs, and it is beginning to be accepted that local chronic inflammation generates a microenvironment that fosters the development of UFs. […] The consideration of UFs as a chronic inflammatory disease is supported by the presence of high expression of inflammatory cytokines in fibroids, including interleukin (IL)-1, IL-6, IL-13, IL-15, tumor necrosis factor (TNF)-, granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin. […] It has been proposed that a single myometrial stem cell goes through tumorigenic transformation following a cellular insult (genetic hit) and gives rise to daughter leiomyoma stem cell (TIC), which proliferate, undergo self-renewal, and clonally expand in response to steroid hormones via paracrine signaling from surrounding differentiated myometrial and leiomyoma cells.

• #132 New Insights into Molecular Pathogenesis of Uterine Fibroids: From the Lab to a Clinician-Friendly Review | IntechOpen

  https://www.intechopen.com/chapters/1165825

  Several studies have documented a pivotal role of inflammation and myofibroblastic transformation in the pathogenesis of UFs, and it is beginning to be accepted that local chronic inflammation generates a microenvironment that fosters the development of UFs. […] The consideration of UFs as a chronic inflammatory disease is supported by the presence of high expression of inflammatory cytokines in fibroids, including interleukin (IL)-1, IL-6, IL-13, IL-15, tumor necrosis factor (TNF)-, granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin. […] It has been proposed that a single myometrial stem cell goes through tumorigenic transformation following a cellular insult (genetic hit) and gives rise to daughter leiomyoma stem cell (TIC), which proliferate, undergo self-renewal, and clonally expand in response to steroid hormones via paracrine signaling from surrounding differentiated myometrial and leiomyoma cells.

• #133 New Insights into Molecular Pathogenesis of Uterine Fibroids: From the Lab to a Clinician-Friendly Review | IntechOpen

  https://www.intechopen.com/chapters/1165825

  Although alterations in MED12 and HMGA2 have been postulated as the initial insult leading to unregulated cell growth, it is unclear whether these genetic alterations cause the transformation of a myometrial stem cell or simply support already existing leiomyoma stem-progenitor cells. […] Molecular events in myoma biology are regulated through a complex network of interconnected and convergent, intracellular, extracellular, and intercellular pathways.

• #134 New Insights into Molecular Pathogenesis of Uterine Fibroids: From the Lab to a Clinician-Friendly Review | IntechOpen

  https://www.intechopen.com/chapters/1165825

  Several studies have documented a pivotal role of inflammation and myofibroblastic transformation in the pathogenesis of UFs, and it is beginning to be accepted that local chronic inflammation generates a microenvironment that fosters the development of UFs. […] The consideration of UFs as a chronic inflammatory disease is supported by the presence of high expression of inflammatory cytokines in fibroids, including interleukin (IL)-1, IL-6, IL-13, IL-15, tumor necrosis factor (TNF)-, granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin. […] It has been proposed that a single myometrial stem cell goes through tumorigenic transformation following a cellular insult (genetic hit) and gives rise to daughter leiomyoma stem cell (TIC), which proliferate, undergo self-renewal, and clonally expand in response to steroid hormones via paracrine signaling from surrounding differentiated myometrial and leiomyoma cells.

• #135 Uterine fibroid – Wikipedia

  https://en.wikipedia.org/wiki/Uterine_fibroid

  Expansion of uterine fibroids occurs by a slow rate of cell proliferation combined with the production of copious amounts of extracellular matrix. […] A small population of the cells in a uterine fibroid have properties of stem cells or progenitor cells, and contribute significantly to ovarian steroid-dependent growth of fibroids. These stem-progenitor cells are deficient in estrogen receptor and progesterone receptor and instead rely on substantially higher levels of these receptors in surrounding differentiated cells to mediate estrogen and progesterone actions via paracrine signaling.

• #136

  https://link.springer.com/article/10.1007/s43032-022-00960-9

  The identity of the factor(s) and molecular mechanisms involved in the cellular transformation of myometrial cells into leiomyoma remains unknown. […] UFs appear to be estrogen/progesterone-dependent and characterized by excessive production of extracellular matrix. […] Recent findings support the fact that stem cells, growth factors, genetic and epigenetic factors, ovarian steroid hormones, cytokines and chemokines, and ECM components are the key factors involved in the development and growth of UFs. […] The CD44/Stro1++ stem cell-derived organoids self-organize to mimic the in vivo structural organization as smooth muscle actin cells organized to the exterior of the organoid with few labeled cellular structures within the interior. […] The growth of UFs is characterized by slow proliferation and is associated with the increased production and concurrent deposition of extracellular matrix proteins usually in a steroid hormone-dependent manner.

• #137 Role of Senescent Cells in Uterine Fibroid Pathogenesis (SOUL Study) | Clinical Research Trial Listing

  https://www.centerwatch.com/clinical-trials/listings/NCT06135870/role-of-senescent-cells-in-uterine-fibroid-pathogenesis-soul-study

  The investigators are evaluating the role of senescent cells in uterine fibroids. […] Using new cutting-edge computational methods, the investigators have found that small groups of senescent cells in fibroids work in concert with immune cells to produce soluble factors in fibroid tissues to create a feed-forward loop leading to fibrosis. […] This project seeks to unravel key cell-cell communication networks involving senescent and immune cells in fibroids to develop new treatments for uterine fibroids.

• #138 New Insights into Molecular Pathogenesis of Uterine Fibroids: From the Lab to a Clinician-Friendly Review | IntechOpen

  https://www.intechopen.com/chapters/1165825

  Several studies have documented a pivotal role of inflammation and myofibroblastic transformation in the pathogenesis of UFs, and it is beginning to be accepted that local chronic inflammation generates a microenvironment that fosters the development of UFs. […] The consideration of UFs as a chronic inflammatory disease is supported by the presence of high expression of inflammatory cytokines in fibroids, including interleukin (IL)-1, IL-6, IL-13, IL-15, tumor necrosis factor (TNF)-, granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin. […] It has been proposed that a single myometrial stem cell goes through tumorigenic transformation following a cellular insult (genetic hit) and gives rise to daughter leiomyoma stem cell (TIC), which proliferate, undergo self-renewal, and clonally expand in response to steroid hormones via paracrine signaling from surrounding differentiated myometrial and leiomyoma cells.

• #139

  https://link.springer.com/article/10.1007/s43032-022-00960-9

  The identity of the factor(s) and molecular mechanisms involved in the cellular transformation of myometrial cells into leiomyoma remains unknown. […] UFs appear to be estrogen/progesterone-dependent and characterized by excessive production of extracellular matrix. […] Recent findings support the fact that stem cells, growth factors, genetic and epigenetic factors, ovarian steroid hormones, cytokines and chemokines, and ECM components are the key factors involved in the development and growth of UFs. […] The CD44/Stro1++ stem cell-derived organoids self-organize to mimic the in vivo structural organization as smooth muscle actin cells organized to the exterior of the organoid with few labeled cellular structures within the interior. […] The growth of UFs is characterized by slow proliferation and is associated with the increased production and concurrent deposition of extracellular matrix proteins usually in a steroid hormone-dependent manner.

• #140 New Insights into Molecular Pathogenesis of Uterine Fibroids: From the Lab to a Clinician-Friendly Review | IntechOpen

  https://www.intechopen.com/chapters/1165825

  Although alterations in MED12 and HMGA2 have been postulated as the initial insult leading to unregulated cell growth, it is unclear whether these genetic alterations cause the transformation of a myometrial stem cell or simply support already existing leiomyoma stem-progenitor cells. […] Molecular events in myoma biology are regulated through a complex network of interconnected and convergent, intracellular, extracellular, and intercellular pathways.

• #141 Hormones and pathogenesis of uterine fibroids | Obgyn Key

  https://obgynkey.com/hormones-and-pathogenesis-of-uterine-fibroids/

  The blockade of pituitary gonadotropin release with gonadotropin-releasing hormone (GnRH) analogs or antagonist is an effective strategy to control fibroid symptoms and arrest their growth. […] The most probable explanation for the effectiveness of this therapy is ovarian blockade and the consequent decrease in circulating estradiol and progesterone levels. […] Mifepristone, asoprisnil, and ulipristal are selective PR modulators that have been shown in clinical trials to inhibit fibroid growth.

• #142 Uterine fibroids: an update on current and emerging medical treatment | TCRM

  https://www.dovepress.com/uterine-fibroids-an-update-on-current-and-emerging-medical-treatment-o-peer-reviewed-fulltext-article-TCRM

  Uterine fibroids are the most common gynecological disorder, classically requiring surgery when symptomatic. […] A major step forward was achieved when peptide analogs of the GnRH were introduced, first those with superagonist properties and subsequently those acting as antagonists. […] Because both types of analogs produce hypoestrogenism, their use is limited to a maximum of 6 months and, for this reason, today they are utilized as an adjuvant treatment before surgery with overall good results. […] Over the last decade, new, nonpeptidic, orally active GnRH-receptor blockers have also been synthesized. […] Another fundamental development has been the utilization of the so-called selective progesterone receptor modulators, sometimes referred to as antiprogestins. […] Large clinical trials have proven the effectiveness of Ulipristal in the long-term medical therapy of fibroids, although some caution must be exercised because of the rare occurrence of liver complications.

• #143 Uterine Fibroids Review: Understanding their Origins to Better Un

  https://www.longdom.org/open-access/uterine-fibroids-review-understanding-their-origins-to-better-understand-their-future-treatments-42568.html

  The available evidence continues to reinforce the importance of progesterone in the development of fibroids (suggesting that estrogens are required, but not sufficient, to stimulate fibroid proliferation). […] The Ulipristal Acetate mediated volume reduction is due to a series of multifactorial and successive events that lead to a low proliferation rate, a transient stimulation of cell death that is not dependent on caspase 3 and a dramatic reduction in the ECM (especially notable after long-term treatment), which could be partially explained by the increased MMP2 expression.

• #144 Uterine fibroids: an update on current and emerging medical treatment | TCRM

  https://www.dovepress.com/uterine-fibroids-an-update-on-current-and-emerging-medical-treatment-o-peer-reviewed-fulltext-article-TCRM

  All selective progesterone receptor modulators produce unique endometrial changes that are today considered benign, reversible, and without negative consequences. […] In conclusion, long-term medical treatment of fibroids seems possible today, especially in premenopausal women. […] The situation is complex because it seems that P exerts a dual action on myomas: it stimulates their growth through upregulating expression of EGF and B-cell lymphoma 2 (Bcl-2) and it inhibits growth through downregulation of insulin-like growth factors (IGF) expression in the cells. […] In terms of mechanism of action, beside the inhibition of estrogen synthesis, this treatment seems to cause DNA damage in myomas cells. […] In terms of mechanism of action, Chen et al demonstrated the presence of mRNAs encoding for GnRHR and EGF in cultured leiomyoma cells. […] In conclusion, this preliminary study documented that Elagolix significantly reduced heavy menstrual bleeding in women with fibroids; in addition, low-dose add-back regimens substantially reduced flashing.

• #145 Uterine fibroids: an update on current and emerging medical treatment | TCRM

  https://www.dovepress.com/uterine-fibroids-an-update-on-current-and-emerging-medical-treatment-o-peer-reviewed-fulltext-article-TCRM

  Uterine fibroids are the most common gynecological disorder, classically requiring surgery when symptomatic. […] A major step forward was achieved when peptide analogs of the GnRH were introduced, first those with superagonist properties and subsequently those acting as antagonists. […] Because both types of analogs produce hypoestrogenism, their use is limited to a maximum of 6 months and, for this reason, today they are utilized as an adjuvant treatment before surgery with overall good results. […] Over the last decade, new, nonpeptidic, orally active GnRH-receptor blockers have also been synthesized. […] Another fundamental development has been the utilization of the so-called selective progesterone receptor modulators, sometimes referred to as antiprogestins. […] Large clinical trials have proven the effectiveness of Ulipristal in the long-term medical therapy of fibroids, although some caution must be exercised because of the rare occurrence of liver complications.

• #146 Uterine fibroids: an update on current and emerging medical treatment | TCRM

  https://www.dovepress.com/uterine-fibroids-an-update-on-current-and-emerging-medical-treatment-o-peer-reviewed-fulltext-article-TCRM

  All selective progesterone receptor modulators produce unique endometrial changes that are today considered benign, reversible, and without negative consequences. […] In conclusion, long-term medical treatment of fibroids seems possible today, especially in premenopausal women. […] The situation is complex because it seems that P exerts a dual action on myomas: it stimulates their growth through upregulating expression of EGF and B-cell lymphoma 2 (Bcl-2) and it inhibits growth through downregulation of insulin-like growth factors (IGF) expression in the cells. […] In terms of mechanism of action, beside the inhibition of estrogen synthesis, this treatment seems to cause DNA damage in myomas cells. […] In terms of mechanism of action, Chen et al demonstrated the presence of mRNAs encoding for GnRHR and EGF in cultured leiomyoma cells. […] In conclusion, this preliminary study documented that Elagolix significantly reduced heavy menstrual bleeding in women with fibroids; in addition, low-dose add-back regimens substantially reduced flashing.

• #147 Update on the Role and Regulatory Mechanism of Extracellular Matrix in the Pathogenesis of Uterine Fibroids

  https://www.mdpi.com/1422-0067/24/6/5778

  Numerous studies demonstrated that TGF-β signaling plays an important role in the pathogenesis of UFs. […] Abnormal ECM accumulation and deposition have been shown to be associated with the activation of TGF-β signaling in UFs. […] The ECM acts as a reservoir of profibrotic growth factors and enhances their activity by increasing their stability and prolonging signaling duration. […] The significant variations in the quantity and distribution of the ECM also create variation in the degree of UF tissue stiffness from soft to firm to solid to hard, with a major impact on the gene expression and biology of these tumor lesions. […] Pharmacological drugs can suppress the UF phenotype by inhibiting ECM production via multiple mechanisms, including epigenetics. […] However, several aspects need to be further elucidated, including characterizing the functional interaction of ECM-secreted cells with other types of cells, elucidating the impact of ECM on the microenvironment, and investigating the molecular and functional structure of ECM that regulates mechanotransduction and stiffness in both UFs and the at-risk MM.

• #148 Update on the Role and Regulatory Mechanism of Extracellular Matrix in the Pathogenesis of Uterine Fibroids

  https://www.mdpi.com/1422-0067/24/6/5778

  Numerous studies demonstrated that TGF-β signaling plays an important role in the pathogenesis of UFs. […] Abnormal ECM accumulation and deposition have been shown to be associated with the activation of TGF-β signaling in UFs. […] The ECM acts as a reservoir of profibrotic growth factors and enhances their activity by increasing their stability and prolonging signaling duration. […] The significant variations in the quantity and distribution of the ECM also create variation in the degree of UF tissue stiffness from soft to firm to solid to hard, with a major impact on the gene expression and biology of these tumor lesions. […] Pharmacological drugs can suppress the UF phenotype by inhibiting ECM production via multiple mechanisms, including epigenetics. […] However, several aspects need to be further elucidated, including characterizing the functional interaction of ECM-secreted cells with other types of cells, elucidating the impact of ECM on the microenvironment, and investigating the molecular and functional structure of ECM that regulates mechanotransduction and stiffness in both UFs and the at-risk MM.

• #149 Endocrine-Disrupting Chemicals and Vitamin D Deficiency in the Pathogenesis of Uterine Fibroids

  https://aprh.journals.ekb.eg/article_166066.html

  Our recent studies demonstrated that early-life EDC exposure reprogrammed the MMSCs toward a pro-fibroid landscape and altered the DNA repair and inflammation pathways. […] Notably, Vitamin D3 (VITD3) as a natural compound shrank the UF growth concomitantly with the reversion of several abnormal biological pathways. […] It ameliorated the developmental exposure-induced DNA damage and pro-inflammation pathway in primed MMSCs. […] This review highlights and emphasizes the importance of multiple pathway interactions in the context of hypovitaminosis D at the MMSCs level and provides proof-of-concept information that can help develop a safe, long-term, durable, and non-surgical therapeutic option for UFs.

• #150 Hormones and pathogenesis of uterine fibroids | Obgyn Key

  https://obgynkey.com/hormones-and-pathogenesis-of-uterine-fibroids/

  The blockade of pituitary gonadotropin release with gonadotropin-releasing hormone (GnRH) analogs or antagonist is an effective strategy to control fibroid symptoms and arrest their growth. […] The most probable explanation for the effectiveness of this therapy is ovarian blockade and the consequent decrease in circulating estradiol and progesterone levels. […] Mifepristone, asoprisnil, and ulipristal are selective PR modulators that have been shown in clinical trials to inhibit fibroid growth.

• #151 Update on the Role and Regulatory Mechanism of Extracellular Matrix in the Pathogenesis of Uterine Fibroids

  https://www.mdpi.com/1422-0067/24/6/5778

  Numerous studies demonstrated that TGF-β signaling plays an important role in the pathogenesis of UFs. […] Abnormal ECM accumulation and deposition have been shown to be associated with the activation of TGF-β signaling in UFs. […] The ECM acts as a reservoir of profibrotic growth factors and enhances their activity by increasing their stability and prolonging signaling duration. […] The significant variations in the quantity and distribution of the ECM also create variation in the degree of UF tissue stiffness from soft to firm to solid to hard, with a major impact on the gene expression and biology of these tumor lesions. […] Pharmacological drugs can suppress the UF phenotype by inhibiting ECM production via multiple mechanisms, including epigenetics. […] However, several aspects need to be further elucidated, including characterizing the functional interaction of ECM-secreted cells with other types of cells, elucidating the impact of ECM on the microenvironment, and investigating the molecular and functional structure of ECM that regulates mechanotransduction and stiffness in both UFs and the at-risk MM.

• #152 Uterine Fibroids – Brigham and Women’s Hospital

  https://www.brighamandwomens.org/obgyn/minimally-invasive-gynecologic-surgery/uterine-fibroids

  Another alternative is using the da Vinci robot for the myomectomy. The da Vinci robot consists of 3 to 4 mechanical arms that are controlled by the surgeon from a separate control unit (console). The arms of the robot can carry various instruments and the instruments can move freely at the tip, allowing much more freedom of movement than with traditional laparoscopy. […] Uterine artery embolization is performed by an interventional radiologist. A small catheter is placed into a blood vessel in the groin and it threaded up to the uterine artery under x-ray guidance. Once the catheter is in the right place, small particles are released into the blood stream that subsequently become stuck in the blood vessels supplying the fibroids. This reduces or stops blood flow to the fibroids, which in turn causes them to die and shrink. […] The UFE procedure itself usually takes about one hour to complete. UFE is very effective in properly selected patients, with over 85% of patients reporting significant improvement in symptoms, even up to 5 years after treatment.

• #153 Uterine Fibroids – Brigham and Women’s Hospital

  https://www.brighamandwomens.org/obgyn/minimally-invasive-gynecologic-surgery/uterine-fibroids

  Another alternative is using the da Vinci robot for the myomectomy. The da Vinci robot consists of 3 to 4 mechanical arms that are controlled by the surgeon from a separate control unit (console). The arms of the robot can carry various instruments and the instruments can move freely at the tip, allowing much more freedom of movement than with traditional laparoscopy. […] Uterine artery embolization is performed by an interventional radiologist. A small catheter is placed into a blood vessel in the groin and it threaded up to the uterine artery under x-ray guidance. Once the catheter is in the right place, small particles are released into the blood stream that subsequently become stuck in the blood vessels supplying the fibroids. This reduces or stops blood flow to the fibroids, which in turn causes them to die and shrink. […] The UFE procedure itself usually takes about one hour to complete. UFE is very effective in properly selected patients, with over 85% of patients reporting significant improvement in symptoms, even up to 5 years after treatment.

• #154 Pathophysiology of uterine fibroids

  https://www.contemporaryobgyn.net/view/pathophysiology-of-uterine-fibroids

  A better understanding of the pathophysiology of uterine fibroids (UFs) will enable healthcare providers to deliver high-quality informed care to their patients, according to Ayman Al-Hendy, MD, PhD, a professor of ob/gyn at Pritzker School of Medicine, University of Chicago. […] Pathophysiology also enables providers to understand the mechanism of action of the various treatment tools, so they can tailor and match an appropriate treatment to a specific patient, Al-Hendy told Contemporary OB/GYN. […] The key pathways are estrogen, progesterone, DNA damage, transforming growth factor beta, growth factors, the canonical Wnt pathway and extracellular matrix (ECM) remodeling. […] But we have limited safe treatment options for fibroid patients who want to preserve their fertility potential, Al-Hendy said. We also do not understand how fibroids cause heavy menstrual bleeding or infertility. […] Investigating genetic correlations and shared loci sheds light on potential causal relationships between reproductive traits and uterine leiomyomata, offering insights into their complex interplay and urging further mechanistic exploration.

• #155 Uterine fibroid: from pathogenesis to clinical management | Obgyn Key

  https://obgynkey.com/uterine-fibroid-from-pathogenesis-to-clinical-management/

  Uterine fibroid or leiomyoma is the most common benign gynecological tumor in premenopausal women (1525%). […] The hypothesis of generation of leiomyoma stem cells, the role of epigenetic/cytogenetic anomalies/mutations, and the overexpression of micro-RNA are of great interest in exploring increased cell proliferation and excessive formation of extracellular matrix. […] The role of sex steroid hormones (estrogens, progesterone) still remains a key point in the pathogenesis of uterine leiomyoma, and, particularly, estrogen receptors (ERs) and progesterone receptors (PRs) play a role in the development and maintenance of tumor growth, and new receptor modulators are attractive for the medical treatment of uterine fibroid. […] Estrogens and progesterone act via a large group of growth factors (in particular, the family of transforming growth factor beta (TGFB)), which in turn by activation of multiple signaling pathways regulate major cellular processes, including proliferation, angiogenesis and fibrosis; these have stimulated an interest toward the development of new drugs. […] Future studies should focus on the use of different alternative procedures (MRI-guided, US laser) and the development of new SPRM or novel non-hormonal drugs, thereby increasing the possibility of tailoring the treatment of uterine fibroids.

• #156 Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3791844/

  Uterine leiomyomas (fibroids or myomas) are benign tumors of uterus and clinically apparent in a large part of reproductive aged women. […] Despite the prevalence of this condition, myoma research is underfunded compared to other nonmalignant diseases. To date, several pathogenetic factors such as genetics, microRNA, steroids, growth factors, cytokines, chemokines, and extracellular matrix components have been implicated in the development and growth of leiomyoma. […] Nowadays, conflicting data about the pathogenesis of leiomyomas coexist in the literature. The development of uterine myomas can be linked to predisposing risk factors, initiators and genetic mechanisms, promoters, and effectors. […] Even if many risk factors suggested by epidemiologic studies have linked uterine leiomyomas to the effects of estrogens and progesterone levels and their metabolism, other mechanisms may be involved in fibroids pathogenesis.

• #157 New Insights into Molecular Pathogenesis of Uterine Fibroids: From the Lab to a Clinician-Friendly Review | IntechOpen

  https://www.intechopen.com/chapters/1165825

  Although alterations in MED12 and HMGA2 have been postulated as the initial insult leading to unregulated cell growth, it is unclear whether these genetic alterations cause the transformation of a myometrial stem cell or simply support already existing leiomyoma stem-progenitor cells. […] Molecular events in myoma biology are regulated through a complex network of interconnected and convergent, intracellular, extracellular, and intercellular pathways.

• #158 Uterine Fibroids: The Science Behind Their Growth and Development

  https://www.linkedin.com/pulse/uterine-fibroids-science-behind-growth-development-bansal-nkc1f

  Emerging research suggests that the immune system may play a role in the pathogenesis of uterine fibroids. […] While genetic and hormonal factors are primary contributors to fibroid development, certain environmental and lifestyle factors can also influence the pathogenesis of uterine leiomyomas. […] The pathogenesis of uterine leiomyomas is multifaceted, involving genetic predisposition, hormonal influence, growth factors, ECM remodeling, vascular changes, immune system factors, and environmental/lifestyle factors.

• #159

  https://link.springer.com/article/10.1007/s43032-022-00960-9

  Uterine fibroids (UFs) (leiomyomas or myomas) are the most common clonal neoplasms of the uterus in women of reproductive age worldwide. […] UFs originate from myometrium consist of smooth muscle and fibroblast components, in addition to a substantial amount of fibrous extracellular matrix which all contribute to the pathogenetic process. […] The prevailing model for UF pathogenesis invokes the genetic transformation of a single myometrial stem cell (MMSC) into a tumor-initiating cell that seeds and sustains clonal tumor growth, characterized by an increase in cell size and number and abundant extracellular matrix production, under the influence of endocrine, autocrine, and paracrine growth factors and hormone receptor signaling. […] Most importantly, the fibroid stem cells acquire the mutations in the gene encoding Mediator complex subunit MED12 and are dominant drivers of UFs in women of diverse racial and ethnic origins.

• #160 New Insights into Molecular Pathogenesis of Uterine Fibroids: From the Lab to a Clinician-Friendly Review | IntechOpen

  https://www.intechopen.com/chapters/1165825

  Several studies have documented a pivotal role of inflammation and myofibroblastic transformation in the pathogenesis of UFs, and it is beginning to be accepted that local chronic inflammation generates a microenvironment that fosters the development of UFs. […] The consideration of UFs as a chronic inflammatory disease is supported by the presence of high expression of inflammatory cytokines in fibroids, including interleukin (IL)-1, IL-6, IL-13, IL-15, tumor necrosis factor (TNF)-, granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin. […] It has been proposed that a single myometrial stem cell goes through tumorigenic transformation following a cellular insult (genetic hit) and gives rise to daughter leiomyoma stem cell (TIC), which proliferate, undergo self-renewal, and clonally expand in response to steroid hormones via paracrine signaling from surrounding differentiated myometrial and leiomyoma cells.

• #161 Uterine fibroids (leiomyomas): Histology and pathogenesis – UpToDate

  https://www.uptodate.com/contents/uterine-fibroids-leiomyomas-histology-and-pathogenesis/print

  Uterine fibroids (leiomyomas) are the most common pelvic neoplasm in females. They are nonmalignant monoclonal tumors arising from the smooth muscle cells of the myometrium. The pathogenesis of leiomyomas is not well understood. Genetic predisposition, environmental factors, steroid hormones, and growth factors important in fibrotic processes and angiogenesis all play a role in the formation and growth of uterine fibroids. […] The disease is heterogeneous, and different fibroids within the same uterus may have different etiologies and arise from different somatic mutations. […] Leiomyoma-related effects on the function and structure of the endometrium are the final common pathways in the pathogenesis of excessive bleeding in myomatous uteri, and there is evidence of both histologic changes in the endometrium and endometrial vasculature in these uteri. […] The pathogenesis of uterine leiomyomas is reviewed here. At least two distinct components contribute to leiomyoma development.

• #162 Uterine Fibroids Initiation and Pathogenesis | Endocrine Society

  https://www.endocrine.org/journals/endocrine-reviews/uterine-fibroids-initiation-and-pathogenesis

  Uterine fibroids are benign monoclonal neoplasms of the myometrium, representing the most common tumors in women worldwide. […] To date, no long-term or noninvasive treatment option exists for hormone-dependent uterine fibroids, due to the limited knowledge about the molecular mechanisms underlying the initiation and development of uterine fibroids. […] This paper comprehensively summarizes the recent research advances on uterine fibroids, focusing on risk factors, development origin, pathogenetic mechanisms, and treatment options. […] Deeper mechanistic insights into tumor etiology and the complexity of uterine fibroids can contribute to the progress of newer targeted therapies.

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