Materiały źródłowe

• #1 Pelvic Organ Prolapse – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563229/

  Pelvic organ prolapse (POP) is a gynecological condition in which the pelvic organs herniate into the vagina due to ligament or muscular weakness. […] Although the etiology of POP is multifactorial, there is a high correlation between pregnancy and vaginal delivery, which can lead to direct pelvic floor muscle and connective tissue injury. […] Additionally, prior pelvic surgeries or conditions associated with sustained episodes of increased intrabdominal pressure, such as heavy lifting, obesity, chronic cough, and constipation, can increase the risk of developing POP. […] DeLancey demonstrated that normal pelvic support is provided by the interaction between the levator ani muscle group and connective tissue attachments that stabilize the vagina at varying levels. Any weakness or tears within the connective tissue leads to the varying pathology of pelvic floor defects.

• #2 Pelvic Organ Prolapse – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563229/

  With normal pelvic support, the vagina lies horizontally on top of the levator and muscles. Damage causes the levator ani muscles to become more vertical in orientation, opening the vagina and thus shifting support to the connective tissue attachments. […] Through biomechanical modeling, it was postulated that the second stage of labor causes the levator ani muscles to stretch more than 200% beyond the threshold for injury. […] Pelvic organ prolapse (POP) is a common condition that is multifactorial in etiology. […] Combinations of anatomical, physiological, genetic, lifestyle, and reproductive factors contribute to pelvic floor dysfunction throughout a woman’s lifespan. […] Many studies have correlated parity with a high incidence of POP.

• #3 Pathophysiology of Pelvic Organ Prolapse | IntechOpen

  https://www.intechopen.com/chapters/60935

  Chronically raised intra-abdominal pressure such as chronic constipation, higher body mass index (BMI), chronic cough, and repetitive heavy weight lifting seems to play a role in POP pathogenesis. […] Risk of subsequent pelvic organ prolapse is increased by hysterectomy however it takes years for development of symptomatic prolapse. […] DeLancey has described vaginal connective tissue support of the pelvis into three levels that help to understand various clinical manifestations of pelvic organ support dysfunction. […] Comprehensively, it has been reviewed that abnormal synthesis or degradation of collagen and elastin fibers of the vaginal wall contributes to the pathophysiology of prolapse. […] The matrix metalloproteinases (MMPs) is proteolytic enzyme involved in both physiological and pathological tissue remodeling in women with and without prolapse.

• #4 SciELO Brazil – Narrative review of the epidemiology, diagnosis and pathophysiology of pelvic organ prolapse Narrative review of the epidemiology, diagnosis and pathophysiology of pelvic organ prolapse

  https://www.scielo.br/j/ibju/a/mHJtzHfncRm5ZXQV3zKPbmG/

  Several risk factors have been associated with POP. All risk factors contribute to weakening of the pelvic floor connective tissue/collagen, causing the pelvic organs to prolapse through the vaginal walls and pelvic floor. […] Weakness of the endopelvic fascia is the main factor in the etiology of POP and all the known risk factors actually cause weakness and damage of the fascia and therefore may result in herniation of the organs and prolapse. […] The Integral theory of Petros and the Levels of Support model of Delancey enable us to locate the defect, diagnose and treat pelvic organ prolapse. […] The Integral Theory represents the foundation of our current knowledge of the development of POP. Published by Peter Petros in 1990, it is the cornerstone of our understanding of the pathogenesis of prolapse as well as the definition of the treatment. According to this theory, POP and its related symptoms result from over-laxity of the vaginal connective tissue or its supporting ligaments.

• #5 Pathophysiology of pelvic organ prolapse – PubMed

  https://pubmed.ncbi.nlm.nih.gov/9921555/

  Pelvic organ prolapse is usually caused by weakness of the pelvic diaphragm. Descent of the pelvic diaphragm places stress on the endopelvic connective tissue support system. Subsequent increases in intra-abdominal pressure result in prolapse. In the majority of cases, labor and childbirth are thought to be the primary factors responsible for pelvic neuropathies and tissue damage that predispose to the development of POP. Certain connective tissue defects, congenital defects, and operative procedures also contribute to pelvic support defects.

• #6 Pelvic Organ Prolapse | AAFP

  https://www.aafp.org/pubs/afp/issues/2017/0801/p179.html

  Pelvic organ prolapse is the descent of one or more of the anterior vaginal wall, posterior vaginal wall, the uterus (cervix), or the apex of the vagina (vaginal vault or cuff scar after hysterectomy). Prevalence increases with age. The cause of prolapse is multifactorial but is primarily associated with pregnancy and vaginal delivery, which lead to direct pelvic floor muscle and connective tissue injury. Hysterectomy, pelvic surgery, and conditions associated with sustained episodes of increased intra-abdominal pressure, including obesity, chronic cough, constipation, and repeated heavy lifting, also contribute to prolapse. […] The cause of pelvic organ prolapse is multifactorial, but pregnancy is the most commonly associated risk factor. Normal pelvic support is primarily provided by the levator ani muscles and the connective tissue attachments of the vagina to the sidewalls and pelvis. With normal pelvic support, the vagina lies horizontally atop the levator ani muscles. When damaged, the levator ani muscles become more vertical in orientation and the vaginal opening widens, shifting support to the connective tissue attachments. Biomechanical modeling has demonstrated that during the second stage of labor, levator ani muscles are stretched more than 200% beyond the threshold for stretch injuries.

• #7 Pelvic Organ Prolapse | AAFP

  https://www.aafp.org/pubs/afp/issues/2017/0801/p179.html

  A magnetic resonance imaging study of parous women revealed that those with prolapse within 1 cm of the hymen are 7.3 times more likely to have levator ani injuries than women without prolapse. Prospective ultrasound studies of initially nulliparous women revealed that the prevalence of levator ani injuries is 21% to 36% after vaginal delivery, and that these injuries correlate with prolapse symptoms. Of note, 17% of nulliparous women with prolapse have levator ani injuries visible on magnetic resonance imaging.

• #8 Uterine Prolapse: Background, History of the Procedure, Problem

  https://emedicine.medscape.com/article/797295-overview

  Pelvic floor defects are created as a result of childbirth and are caused by the stretching and tearing of the endopelvic fascia and the levator muscles and perineal body. Partial pudendal and perineal neuropathies are also associated with labor. […] Impaired nerve transmission to the muscles of the pelvic floor may predispose them to decreased tone, leading to further sagging and stretching. Therefore, multiparous women are at particular risk for UP. Genital atrophy and hypoestrogenism also play important contributory roles in the pathogenesis of prolapse. However, the exact mechanisms are not completely understood. Prolapse may also result from pelvic tumors, sacral nerve disorders, and diabetic neuropathy. […] Other medical conditions that may result in prolapse are those associated with increases in intra-abdominal pressure (eg, obesity, chronic pulmonary disease, smoking, constipation). Certain rare abnormalities in connective tissue (collagen), such as Marfan disease, have also been linked to genitourinary prolapse. […] A review of the detailed mechanisms that can lead to UP is beyond the scope of this article. However, thorough evaluation and definition of all support defects is of critical importance because most women with UP have multiple defects.

• #9 Pelvic Organ Prolapse | AAFP

  https://www.aafp.org/pubs/afp/issues/2010/0501/p1111.html

  Pelvic organ prolapse, or genital prolapse, is the descent of one or more of the pelvic structures (bladder, uterus, vagina) from the normal anatomic location toward or through the vaginal opening. The cause is a loss of pelvic support from multiple factors, including direct injury to the levator ani, as well as neurologic injury from stretching of the pudendal nerves that may occur with vaginal childbirth. […] The cause of pelvic organ prolapse is multi-factorial, resulting from loss of the support maintained by a complex interaction among the levator ani, the vagina, and the connective tissue, as well as neurologic injury from stretching of the pudendal nerves that may occur during childbirth. […] When the levator ani loses tone, it moves from a horizontal to a semi-vertical position, creating a widened genital hiatus (i.e., the distance between the external urethral meatus and the posterior midline hymen) that forces the pelvic structures to rely on connective tissue for support. When the connective tissue support also fails, as a result of possible collagen decrease and tearing, prolapse may occur.

• #10 Pathophysiology of Pelvic Organ Prolapse | IntechOpen

  https://www.intechopen.com/chapters/60935

  Chronically raised intra-abdominal pressure such as chronic constipation, higher body mass index (BMI), chronic cough, and repetitive heavy weight lifting seems to play a role in POP pathogenesis. […] Risk of subsequent pelvic organ prolapse is increased by hysterectomy however it takes years for development of symptomatic prolapse. […] DeLancey has described vaginal connective tissue support of the pelvis into three levels that help to understand various clinical manifestations of pelvic organ support dysfunction. […] Comprehensively, it has been reviewed that abnormal synthesis or degradation of collagen and elastin fibers of the vaginal wall contributes to the pathophysiology of prolapse. […] The matrix metalloproteinases (MMPs) is proteolytic enzyme involved in both physiological and pathological tissue remodeling in women with and without prolapse.

• #11

  https://journals.lww.com/indianjurol/fulltext/2006/22040/pathophysiology_of_pelvic_organ_prolapse_and.3.aspx

  Pelvic organ prolapse is a common and distressing condition. It occurs when there is a weakness in the supporting structures of the pelvic floor allowing the pelvic viscera to descend. […] Damage to the muscular and fascial supports of the pelvic floor as a result of pregnancy and childbirth contributes to the development of prolapse. […] The biochemical properties of the connective tissue may also play an important role in the development of prolapse. There is evidence to link clinical and laboratory abnormalities of collagen to pelvic organ prolapse. […] There is a known reduction in tissue collagen content following menopause. […] Chronically increased intraabdominal pressure caused by repetitive straining will exacerbate any potential weaknesses in the pelvic floor and is also associated with an increased risk of prolapse.

• #12 Pelvic Organ Prolapse: Types, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/24046-pelvic-organ-prolapse

  Having a heavier body weight. Studies have shown that people who have overweight or obesity are more likely to develop POP than people who are within a weight range thats healthy for them. […] Long-term pressure in your abdominal cavity. Pressure on your pelvic floor muscles can weaken them. […] Family history. Research into the genetic components of POP is ongoing, but its possible that you inherited a weaker pelvic floor. […] Connective tissue diseases. People with conditions like Ehlers-Danlos syndrome, Marfan syndrome or joint hypermobility syndrome are at risk of POP.

• #13 Understanding Pelvic Organ Prolapse: A Comprehensive Review of Etiology, Epidemiology, Comorbidities, and Evaluation

  https://www.mdpi.com/2563-6499/6/1/6

  Obstetric factors, such as vaginal childbirth, are widely recognized as significant risk factors for POP. The process of childbirth can cause damage to the pelvic floor muscles, nerves, and connective tissues, leading to long-term weakening and increased susceptibility to prolapse. […] The association between hysterectomy and subsequent POP has always been controversial and influenced by factors such as age, existing prolapse at hysterectomy, and surgical approach, including apical support. […] Lifestyle factors, such as obesity, chronic constipation, and heavy lifting, can also contribute to the development of pelvic organ prolapse. […] Finally, age-related changes, including the natural decline in muscle tone and connective tissue strength, play a significant role in the etiology of pelvic organ prolapse. As women age, the pelvic floor muscles and connective tissues gradually lose their elasticity and ability to support the pelvic organs, leading to an increased risk of prolapse.

• #14 Pelvic organ prolapse – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/pelvic-organ-prolapse/

  Pelvic organ prolapse (POP) is the protrusion of the uterus, vaginal apex, or surrounding pelvic structures (e.g., bladder, rectum) into the vaginal vault due to decreased pelvic floor support. […] Other risk factors include multiparity (particularly vaginal births), prior pelvic surgery, connective tissue disorders, and increased intra-abdominal pressure secondary to obesity or chronic constipation. […] Etiology: : insufficiency of the pelvic floor muscles and the ligamentous supportive structure of the uterus and vagina (low-tone pelvic floor dysfunction). […] Risk factors include older age, multiple vaginal deliveries and/or traumatic births (greatest risk factor), low estrogen levels (e.g., during menopause), and increased intra-abdominal pressure (due to, e.g., obesity; cough related to chronic lung disease and/or smoking, ascites, pelvic tumors, constipation). […] POP can cause urethral obstruction; advise patients that treatment may relieve the obstruction, unmasking stress urinary incontinence. […] Repair with synthetic mesh and/or grafting is no longer recommended for most individuals with POP because of the high risk of complications.

• #15 SciELO Brazil – Narrative review of the epidemiology, diagnosis and pathophysiology of pelvic organ prolapse Narrative review of the epidemiology, diagnosis and pathophysiology of pelvic organ prolapse

  https://www.scielo.br/j/ibju/a/mHJtzHfncRm5ZXQV3zKPbmG/?lang=en

  Conditions that cause an increase in intra-abdominal pressure such as chronic cough and constipation, obesity, modifiable risk factors such as a lifestyle or occupations that require lifting heavy loads and medical conditions that involve the connective tissue such as Ehlers-Danlos syndrome or Marfan syndrome are considered risk factors for POP.

• #16 Pathophysiology of Pelvic Organ Prolapse | IntechOpen

  https://www.intechopen.com/chapters/60935

  Age has been recognized as an intrinsic factor in the development of pelvic floor dysfunction and most consensuses in favor that it has a role in the etiology of female pelvic organ prolapse (POP). […] The relative prevalence of POP increased by about 40% with every decade of life, as demonstrated by a cross-sectional study of 1004 women (age 1883 years) who attended their yearly examination. […] Age and POP relation is hypothesized to be secondary to numerous factors including physiologic changes of the pelvic floor components and decline in estrogen during the postmenopausal period with advance age. […] There are hormonal induced physiological changes that occur in pelvic floor musculature and connective tissue during pregnancy. […] The causative links between childbirth and prolapse have shown by various epidemiological and observational cohort studies.

• #17 Pelvic organ prolapse – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/pelvic-organ-prolapse/symptoms-causes/syc-20360557

  Pelvic organ prolapse is when one or more pelvic organs drop from their position. This makes a bulge in the vagina, called a prolapse. […] The muscles and connective tissues of the pelvic floor typically hold the pelvic organs in place. Pelvic organ prolapse happens when the muscles and tissues of the pelvic floor weaken. This may be due to pregnancy, childbirth or menopause. […] The cause of pelvic organ prolapse is the weakening of the tissues and the muscles that support the pelvic organs. The most common cause is having a baby vaginally.

• #18 Understanding Pelvic Organ Prolapse: A Comprehensive Review of Etiology, Epidemiology, Comorbidities, and Evaluation

  https://www.mdpi.com/2563-6499/6/1/6

  Pelvic organ prolapse (POP) is a prevalent condition characterized by the descent of one or more pelvic organs, such as the bladder, uterus, or rectum, into the vaginal canal due to weakened pelvic floor support. […] The etiology of pelvic organ prolapse is multifactorial, with a complex interplay of genetic, hormonal, obstetric, lifestyle, and age-related factors contributing to its development. Genetic predisposition plays a significant role in the etiology of pelvic organ prolapse, as studies have shown a strong familial tendency for the condition. […] Hormonal factors, particularly the decline in estrogen levels during the menopausal transition, also contribute to the development of pelvic organ prolapse. Estrogen is crucial for maintaining the strength and integrity of the pelvic floor tissues, and its deficiency can lead to tissue weakening and prolapse.

• #19 Uterine prolapse – Wikipedia

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

  Additionally, the pelvic musculature and connective tissues are estrogen sensitive and respond to changes in estrogen level. Estrogen deficiency, which can occur during menopause, can affect the production of collagen that is needed to build connective tissue that makes up ligaments and fascia, which can contribute to uterine prolapse. This is also a reason that connective tissue disorders can predispose certain people to uterine prolapse.

• #20 Understanding Pelvic Organ Prolapse: A Comprehensive Review of Etiology, Epidemiology, Comorbidities, and Evaluation

  https://www.mdpi.com/2563-6499/6/1/6

  Collagen metabolism is significantly altered in women with prolapse. An alteration in the ratio of collagen types I and III could lead to pelvic floor dysfunction. […] Additionally, connective tissue disorders have been linked to the development of POP. Amongst those, patients with Ehlers–Danlos or Marfan syndrome are at enhanced risk of POP.

• #21 Advances in molecular mechanisms of pelvic organ prolapse (Review)

  https://www.spandidos-publications.com/10.3892/etm.2021.10442

  It is likely that macroscopic parameters, such as anatomy, lifestyle and reproductive factors, interact with microscopic parameters, such as physiology and genetics in the female pelvic floor, leading to POP. […] The molecular mechanisms of POP are complex and have remained to be fully elucidated. They may be divided into the following aspects: i) Reduction of the extracellular matrix (ECM) in pelvic floor connective tissue; ii) activation of oxidative stress (OS); iii) genetic susceptibility; iv) denervation of the pelvic floor; and v) reduction of estrogen infiltration. […] To the best of our knowledge, reduced ECM metabolism in pelvic floor connective tissue, including reduced anabolism and increased catabolism, is the predominant pathogenic mechanism of POP. […] It is reasonable to hypothesize that downregulation of TGF-1 hinders collagen synthesis, interferes with ECM metabolism and ultimately affects the occurrence and development of POP.

• #22 Advances in molecular mechanisms of pelvic organ prolapse (Review)

  https://www.spandidos-publications.com/10.3892/etm.2021.10442

  The above findings suggest that HOXA11 and TGF-1 exert a synergistic effect on the expression of collagen and MMP enzymes. […] The major components of ECM are elastic fibers and collagen. […] Patients with POP exhibit weakened flexibility of elastin and increased flexibility of elastase, which disrupts the mechanical balance of the pelvic floor. […] In summary, the disordered elastic fiber homeostasis may weaken the function of the stent, which is one of the primary events in the pathogenesis of POP. […] A previous study indicated that overexpression of MMP2 is a harmful factor for POP. […] Therefore, MMPs and TIMPs are considered the key factors of regulating ECM degradation. […] In summary, MMP and TIMP functions are balanced in order to regulate ECM anabolism. […] Based on these results, it is hypothesized OS hinders the balance of MMPs/TIMPs and interferes with the TGF-1/Smad pathway, which negatively affects the production of elastic fibers, thereby destroying the pelvic floor support network and ultimately leading to the occurrence of POP.

• #23

  https://link.springer.com/article/10.1007/s00192-008-0737-1

  Little is known about the pathophysiology of pelvic organ prolapse (POP). […] The association between POP and connective tissue metabolism is well established. However, the causality of this association is unclear. […] The characteristics of the pelvic floor connective tissue of POP patients relate to tissue repair. […] To resolve the question of cause and effect, the role of fibroblasts in producing the extracellular matrix should be clarified. […] Recent literature supports the hypothesis of Jackson but does not resolve long-standing questions on the aetiology of POP. […] In 1996, Jackson found that patients with a descent of the cervix to, or beyond the introitus, with associated cystocele, have a reduced collagen content, with a relatively high content of immature collagen cross-links compared to non-POP patients.

• #24 Pathophysiology of Pelvic Organ Prolapse | IntechOpen

  https://www.intechopen.com/chapters/60935

  The pelvic organs are invested by connective tissues that provide the anatomic support of the pelvis and its contents. […] The connective tissues of the vagina and supportive tissues comprise predominantly of fibrillar component (collagen and elastin) embedded in a non-fibrillar component (noncollagenous glycoproteins, hyaluronan, and proteoglycans). […] The ratio of collagen I to III is an indicator of tensile strength: the higher the amount of collagen type I, the higher is the mechanical strength. […] Thus the increased stretchability and distensibility and decline in tensile strength associated with a higher content of collagen III are likely to contribute to the progression of POP.

• #25

  https://link.springer.com/article/10.1007/s00192-008-0737-1

  The content of AGEs is increased in patients with POP, which makes them susceptible for developing POP over time. […] Jackson found no change in the type I to type III ratio. Most studies, however, found an increase in type III and/or a decrease in type I, thus resulting in a decreased I/III ratio. […] An increase in the expression of both collagen type III and MMP-9 expression is typical of tissue that is remodelling after injury or accommodating to a progressively increasing mechanical load. […] The increased flexibility, dispensability and decreased tensile strength associated with an increase in collagen III, together with a decrease in elastin levels, will very likely contribute to the progression of POP.

• #26

  https://link.springer.com/article/10.1007/s00192-008-0737-1

  He concludes that the bulk of this deficient glycated old collagen, which is brittle and susceptible to rupture, is an important aetiologic factor in POP. […] The role of fibroblasts that produce the molecules in the extracellular matrix, such as collagen and elastin, needs further elucidation. […] The objective of this review is to summarise our current understanding of changes in pelvic floor connective tissue in women with POP compared to women without POP. […] The balance between synthesis and degradation of collagen is important for maintaining tissue integrity and tensile strength during continuous tissue remodelling. […] Jackson suggested an increased metabolic turnover of collagen, since MMP-2 and MMP-9 were significantly higher in prolapse tissue than in normal tissue. […] In particular, the breakdown of immature newly formed collagen is increased.

• #27 The role of GPX1 in the pathogenesis of female pelvic organ prolapse | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0181896

  OS(oxidative stress) may be involved in the pathophysiology of POP by contributing to ECM metabolic disorder in a severity-dependent manner in human uterosacral ligament fibroblasts (hUSLFs), possibly through the regulation of MMPs, TIMPs and TGF-1 indirectly. […] Our previous research also found that excess mechanical stress and H2O2 inhibited cell proliferation, and decreased mRNA and protein expression levels of ECM components, collagen 1, collagen 3 and elastin in hUSLFs. […] All of above study showed that Mechanical strain caused abnormalities in ECM metabolism via OS pathway, which may participate in the development of POP. […] This suggested GPX1 may play an important role in the pathophysiology of POP. Thus, the present study aimed to study the role of GPX1 in response to mechanical strain, which may provide insight into the pathogenesis of POP.

• #28 Genetic Etiology in Pelvic Organ Prolapse: Role of Connective Tissue Homeostasis, Hormone Metabolism, and Oxidative Stress

  https://www.mdpi.com/2073-4425/16/1/5

  Genetic factors can act as intrinsic drivers that regulate the growth of pelvic floor and respond to the dramatic and dynamic changes. […] Current studies are devoted to identifying the predisposed genetic variants associated with POP. […] Given the incomplete penetrance, polygenic traits, and small effect sizes of each variant in complex diseases, the evaluation of genetic susceptibility and molecular mechanisms involved in POP is not easy. […] The decline in sex hormone levels with menopause in aging women has negative effects on the female urogenital system, leading to atrophic changes. […] The strength and flexibility of pelvic connective tissues and muscles can also be affected by sex hormones that interact with specific receptors. […] Oxidative stress (OS) is caused by an imbalance in reactive oxygen species (ROS) and antioxidant defense systems in cells, tissues, or organs. […] If their balance is destroyed, ROS can react spontaneously on biomolecules, such as DNA, RNA, protein, and lipids, leading to cell death and disease. […] Therefore, OS interferes with the process of collagen and elastin synthesis.

• #29 Frontiers | Roles and mechanisms of biomechanical-biochemical coupling in pelvic organ prolapse

  https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1303044/full

  Fibroblasts, the primary cellular component of the pelvic floor, exhibit modified cellular attributes in vitro, which influences their dynamic response to external mechanical stimuli. […] The findings suggest a potential mechanism by which the excessive degradation of ECM components contributes to the development and progression of POP. […] These factors lead to an increase in ECM degradation and a decrease in collagen synthesis. […] This weakens the support of pelvic organs and leads to the subsequent development of POP. Fibroblast mechanoreceptor damage promotes POP. […] The cytoskeleton, which is the largest cellular mechanosensor, serves as the primary mechanism for transmitting mechanical stimuli from the extracellular space to the intracellular compartment. […] The changes in F-actin in POP-related fibroblasts are evident. […] The mechanical force applied to healthy hUSLFs induces a POP-like change in morphology. […] Overall, these studies suggest that cell apoptosis is a key mechanism underlying POP development.

• #30 Genome-wide association identifies seven loci for pelvic organ prolapse in Iceland and the UK Biobank | Communications Biology

  https://www.nature.com/articles/s42003-020-0857-9

  A higher prevalence and more recurrent POP is seen in women with joint hypermobility than in others. […] Genetic factors have been estimated to explain 43% of the variation in risk of POP in a twin study. […] We discovered eight variants at seven loci that associate with POP and point to a role of connective tissue metabolism and estrogen in the etiology of POP. […] Two sequence variants, rs3820282 at WNT4 and rs12325192 near SALL1 also associate with other traits that are strongly affected by estrogen exposure, i.e. leiomyoma, gestational duration and endometriosis. […] Rs3791675 at EFEMP1 associates with traits with proposed collagen pathophysiology, i.e. inguinal hernia, ventral hernia and carpal tunnel syndrome. […] The genetic overlap observed between POP and several traits with similar pathophysiology point towards a role of estrogen exposure and connective tissue metabolism in the etiology of POP.

• #31 Advances in molecular mechanisms of pelvic organ prolapse (Review)

  https://www.spandidos-publications.com/10.3892/etm.2021.10442

  The genetic polymorphism of the collagen type III 1 (COL3A1) gene leads to amino acid changes in the cy1 (III) chain, which may interfere with the mechanical properties of type III collagen and affect the supporting structure of the pelvic floor. […] The aforementioned results demonstrated that the ESR1 genotype may be a predisposing factor for POP and that it may be used as a potential therapeutic target for this disease. […] The present review summarized the molecular mechanisms of POP into five aspects, including the metabolism of ECM, OS activation, genetic susceptibility, pelvic floor denervation and reduction of estrogen infiltration.

• #32 Rectocele: Causes, Symptoms, Diagnosis, Stages & Treatment

  https://my.clevelandclinic.org/health/diseases/17415-rectocele

  A rectocele is a condition where the tissue between your rectum and vagina weakens, causing your rectum to bulge onto your vagina’s back wall. […] Rectocele is one form of pelvic organ prolapse (POP), a condition where organs droop because of a weak pelvic floor. […] A rectocele occurs when your pelvic floor weakens. Several factors can contribute: […] Rectocele can worsen without treatment. Not every rectocele requires surgery. Still, depending on the severity of your rectocele, you may need to increase your fiber intake, perform daily Kegel’s, use a pessary, etc. Follow the treatment plan that you and your provider decide works best.

• #33 Pathophysiology Pelvic Organ Prolapse | PDF

  https://www.scribd.com/document/88001846/Pathophysiology-Pelvic-Organ-Prolapse

  Female patients, especially those who are elderly, postmenopausal, or have had multiple pregnancies are predisposed to pelvic organ prolapse. […] Factors like obesity, chronic coughing, smoking, and constipation can further increase intra-abdominal pressure and weaken pelvic muscles and tissues over time, leading to the sagging and descent of pelvic organs through the vaginal opening. […] This can cause symptoms such as vaginal pressure or fullness, pain with sex or urination, and displacement of organs like the bladder or rectum.

• #34 Clinically useful measures for pelvic organ prolapse – O&G Magazine

  https://www.ogmagazine.org.au/16/1/clinically-useful-measures/

  The management of more advanced and symptomatic pelvic organ prolapse (POP) is far more complicated than merely identifying the cause of a patient complaint of a bulge and arranging surgery. It involves the interpretation of possible pathogenesis and all relevant symptoms, signs, POP and intercurrent diagnoses. […] The distortional and pressure effects of uterovaginal prolapse can have significant impact on other pelvic organs, particularly the lower urinary tract and anorectum. As part of this more informed approach to POP surgery, the need for a more comprehensive assessment of the interaction between POP and lower urinary tract function has been increasingly recognised. […] The interpretation of possible pathogenesis and all relevant symptoms, signs, POP and intercurrent diagnoses in cases of more advanced and symptomatic POP can require a tertiary assessment including urodynamics by an appropriately skilled assessor.

• #35 Molecular landscape of pelvic organ prolapse provides insights into disease etiology and clues towards putative novel treatments | medRxiv

  https://www.medrxiv.org/content/10.1101/2020.03.12.20034165v1.full-text

  Pelvic organ prolapse (POP) represents a major health care burden in women but its underlying pathophysiological mechanisms have not been elucidated. […] POP has a multifactorial etiology in which both hereditary and environmental factors play a role. […] The integrated molecular landscape of POP that we built provides insights into the biological processes underlying the disease and clues towards novel treatments. […] The POP landscape reveals four main biological processes that operate in epithelial cells, fibroblasts and surrounding ECM of the female urogenital tract: EMT, immune response activation, ECM modulation, and fibroblast survival and apoptosis. […] The cytokine TGFB1 represents the master regulator as, when activated, it affects and modulates all four biological processes in the landscape.

• #36 Molecular landscape of pelvic organ prolapse provides insights into disease etiology and clues towards putative novel treatments | medRxiv

  https://www.medrxiv.org/content/10.1101/2020.03.12.20034165v1.full-text

  As the master regulator of the landscape, TGFB1 would be an interesting target for developing novel treatments of POP. […] We indeed show that, through downregulating the expression of the key ECM (and landscape) proteins COL1A1, COL3A1 and ELN, metformin counteracts molecular mechanisms downstream of activated TGFB1 that negatively affect POP, as we predicted from the landscape.

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