Materiały źródłowe

• #1 Uterine prolapse – Wikipedia

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

  Uterine prolapse is a form of pelvic organ prolapse in which the uterus and a portion of the upper vagina protrude into the vaginal canal and, in severe cases, through the opening of the vagina. It is most often caused by injury or damage to structures that hold the uterus in place within the pelvic cavity. […] The uterus is normally held in place by the combined effort of pelvic floor muscles, various ligaments, pelvic fascia, and the vaginal wall. The levator ani muscle plays the most significant role in pelvic organ support by acting as a basket that keeps the pelvic organs suspended. […] Uterine prolapse occurs when there is a disruption to any of the structures mentioned above that help hold the uterus in place. Weakening of the levator ani muscles can occur during vaginal childbirth, in which portions of the muscle can detach from the bony pelvis, or through age-related changes to musculature, and this can lead to a loss of support for the uterus.

• #1 Pathophysiology of Pelvic Organ Prolapse | IntechOpen

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

  Morbid obesity was associated with 40% increase in the occurrence of uterine prolapse. […] 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. […] Laxity or damage of these ligaments may nullify the muscle forces causing POP, urinary and bowel dysfunctions. […] 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.

• #1 Uterine prolapse – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/uterine-prolapse/symptoms-causes/syc-20353458

  Supporting ligaments and other connective tissues hold the uterus in place. When these supportive tissues stretch and weaken, the uterus can move out of its original place down into the vagina. This is called a prolapsed uterus. […] Uterine prolapse occurs when pelvic floor muscles and ligaments stretch and weaken until they no longer provide enough support for the uterus. As a result, the uterus slips down into or protrudes out of the vagina. […] Uterine prolapse results from the weakening of pelvic muscles and supportive tissues. Causes of weakened pelvic muscles and tissues include: […] Factors that can increase the risk of uterine prolapse include: […] Uterine prolapse often happens with prolapse of other pelvic organs.

• #1 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. […] The cause of pelvic organ prolapse is multifactorial, but pregnancy is the most commonly associated risk factor. […] Additional risk factors for prolapse are listed in Table 1.

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

  https://emedicine.medscape.com/article/264231-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.

• #1 Uterine prolapse – Wikipedia

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

  Pregnancy, vaginal childbirth, or injury can also stretch and weaken the uterosacral ligaments, leading to poor suspension or positioning of the uterus so that it is no longer supported by pelvic floor muscles. […] 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.

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

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

  Pelvic organ prolapse (POP) is a common gynecological benign disease occurring in middleaged and elderly females. Its incidence increases every year. […] The association between the incidence of POP and the reduction of the extracellular matrix, activation of oxidative stress, genetic susceptibility, denervation of the pelvic floor and reduction of estrogen infiltration were explored. […] 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.

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

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

  OS may cause increased oxidative modification of DNA, lipids and proteins, and induce mitochondrial apoptosis. […] 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. […] 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.

• #1 Role of Fibroblasts and Myofibroblasts on the Pathogenesis and Treatment of Pelvic Organ Prolapse

  https://www.mdpi.com/2218-273X/12/1/94

  Pelvic organ prolapse (POP) is a multifactorial connective tissue disorder caused by damage to the supportive structures of the pelvic floor, leading to the descent of pelvic organs in the vagina. […] In women with POP, fibroblast function is disturbed or altered, which causes impaired collagen metabolism that affects the mechanical properties of the tissue. […] Fibroblast function plays a crucial role in the pathophysiology of POP by directly affecting the connective tissue quality. […] On the other hand, fibroblasts determine the success of the POP treatment, as the fibroblast-to-(myo)fibroblast transition is the key event during wound healing and tissue repair. […] The risk factors for POP are vaginal delivery, pregnancy, or other conditions resulting in increased abdominal pressure, such as obesity, chronic coughing, heavy lifting, constipation, and so on.

• #1 Role of Fibroblasts and Myofibroblasts on the Pathogenesis and Treatment of Pelvic Organ Prolapse

  https://www.mdpi.com/2218-273X/12/1/94

  The collagen metabolism and ECM turnover are controlled by the synthesis or degradation of ECM components, which is important for maintaining tissue integrity. […] Higher MMP-9 expression and increased collagen III in fibroblasts after an injury or after increased applied mechanical load to the pelvic tissues can be an indication of tissue remodeling and supports the hypothesis that POP may be related to disturbed and impaired wound healing. […] The objective of this review is to resolve, if possible, the question of “cause and result” for the fibroblasts in the development and treatment of POP. […] The changes in connective tissue during the development of POP resemble scar tissue by being stiffer and having increased amounts of collagen type III relative to collagen type I protein.

• #1 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). […] 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. […] Normal pelvic support is primarily provided by the levator ani muscles and the connective tissue attachments of the vagina to the sidewalls and pelvis. […] 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.

• #1 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

  Pelvic organ prolapse (POP) is a significant contributor to hysterectomy among middle-aged and elderly women. […] The primary characteristics of POP include compromised mechanical properties of uterine ligaments and dysfunction within the vaginal support structure, often resulting from delivery-related injuries. […] A comprehensive analysis of the literature revealed that the extracellular matrix produced by fibroblasts, as well as their cytoskeleton, undergoes alterations in patient tissues and cellular models of POP. […] The strongest risk factors for POP are pregnancy and vaginal delivery. […] Impaired mechanics of the uterosacral ligament (USL) due to long-term forces is a key tissue in the pathogenesis of POP. […] Numerous studies have shown that the USL and anterior vaginal wall undergo biomechanical stimuli, which activate signal pathways through a series of biochemical reactions, induce structural damage of connective tissues, leading to dysfunction.

• #1 Alignment of the Cervix with the Vagina in Uterine Retroversion: A Possible Risk Factor in Uterine Prolapse

  https://www.mdpi.com/2075-4418/12/6/1428

  Multiple observational studies have found an association of uterine prolapse with uterine retroversion. […] One mechanism proposes that this alignment of the uterus with the vagina would allow the uterus to descend and ascend within the vagina with increases and decreases in intra-abdominal pressure. This piston-like action would create mechanical stress on the supporting structures of the uterus, leading to uterine prolapse and other pelvic floor dysfunctions. […] The presence of this anatomic alignment suggests that these mechanisms take place, which in turn suggests that uterine retroversion is a causative factor for uterine prolapse. […] Damage to the uterosacral ligament, transverse cervical ligament, and the levator ani have all been proposed as factors in uterine prolapse. […] Longitudinal studies of women with uterine retroversion, evaluating the timing of uterine prolapse relative to the timing of uterine retroversion and the timing of events which could cause pelvic floor damage, could help determine which, if any, or if all, of these mechanisms are involved.

• #1 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

  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 strength of collagen, the main component of the body’s connective tissue, and specifically of the pelvic floor fascia and ligaments, is determined by genetic factors. […] The apparent influence of estrogen and SERM on the synthesis of estrogen receptors may explain the contradicting association between SERM and the incidence of POP, most likely by altering the ratio between alpha and beta estrogen receptors.

• #1 Cellular senescence: A pathogenic mechanism of pelvic organ prolapse (Review)

  https://www.spandidos-publications.com/10.3892/mmr.2020.11339

  The main five hallmarks of POP associated with aging were reviewed primarily based on a previous review on the hallmarks of general aging. Genomic instability and imbalanced proteostasis are likely to be the primary triggers of aging-related prolapse. Mitochondrial dysfunction in the progression of senescence may consequentially become the integrated cause of POP. Cell senescence, one facet of the aging process, is a collective phenotype caused by a complex network of signaling pathways. Mechanisms causing fibroblast senescence, including gene instability, mitochondrial dysfunction and altered senescence-symbolized phenotype, provide a basis for senescence-related POP pathological mechanisms.

• #1 Cellular senescence: A pathogenic mechanism of pelvic organ prolapse (Review)

  https://www.spandidos-publications.com/10.3892/mmr.2020.11339

  Pelvic organ prolapse (POP) is a common symptom of pelvic floor disorders which is characterized by the descent of the uterus, bladder or bowel from their normal anatomical position towards or through the vagina. […] The present review provides an integrated overview of the current research and concepts regarding POP, in addition to discussing how fibroblasts can be targeted to evade the negative impact of senescence on POP. However, it is probable that other mechanisms that can also cause POP exist during cell senescence, which necessitates further research and provides new directions in the development of novel medical treatment, stem cell therapy and nonsurgical interventions for POP. […] In summary, the pathogenic mechanism of POP mainly results from the loss of anatomical support during aging.

• #1 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

  The current understanding of the pelvic floor is based on the work of two modern anatomists: Peter Petros and John Delancey. These two researchers have studied the pelvic floor extensively and have incorporated in their studies advanced dynamic imaging techniques. […] According to the integral theory, POP and its related symptoms result from over-laxity of the vaginal connective tissue or its supporting ligaments.

• #1 Uterine prolapse: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/001508.htm

  Uterine prolapse occurs when the womb (uterus) drops down and presses into the vaginal area. […] Muscles, ligaments, and other structures hold the uterus in the pelvis. If these tissues are weak or stretched, the uterus drops into the vaginal canal. This is called prolapse. […] Other things that can cause or lead to uterine prolapse include: Normal aging, Lack of estrogen after menopause, Conditions that put pressure on the pelvic muscles, such as chronic cough and obesity, Pelvic tumor (rare). […] Repeated straining to have a bowel movement due to long-term constipation can make the problem worse. […] Uterine prolapse is mild when the cervix drops into the lower part of the vagina. Uterine prolapse is moderate when the cervix drops out of the vaginal opening. […] There are some surgical procedures that can be done without removing the uterus, such as a sacrospinous fixation. This procedure involves using nearby ligaments to support the uterus.

• #1

  https://step2.medbullets.com/gynecology/121754/uterine-prolapse

  Uterine prolapse occurs when pelvic floor musculature is unable to provide adequate support […] ligaments can stretch and weaken over time […] most important in preventing prolapse […] Pathogenesis […] incomplete prolapse […] uterus drops part way down into the vagina […] creates a bulge […] complete prolapse […] uterus slips down and protrudes out of the vagina […] Kegel exercises […] mechanism […] strengthen pelvic floor musculature […] vaginal pessary […] mechanism […] rubber device that fits around the cervix to help hold the uterus in place […] hysterectomy […] mechanism […] removal of uterus […] sacrohysteropexy […] mechanism […] resuspension of the prolapsed uterus using a mesh sling.

• #1 Pelvic Organ Prolapse – StatPearls – NCBI Bookshelf

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

  The advantages of transvaginal approaches include shorter operative and recovery times, whereas the advantages of abdominal approaches provide more durable outcomes and decrease the risk of recurrence. […] In recent years, the procedure of choice has become the abdominal sacrocolpopexy, which either laparotomy, laparoscopy, or robotic-assisted can do. Since Lane’s initial delineation of the procedure in 1962, the procedure has undergone many modifications.

• #1

  https://scholars.duke.edu/individual/pub1484592

  BACKGROUND: Prolapse recurrence after transvaginal surgical repair is common; however, its mechanisms are ill-defined. […] The primary mechanism of prolapse recurrence following vaginal hysterectomy with uterosacral ligament suspension or VM hysteropexy was apical descent. In addition, greater inferior descent of the vaginal apex and perineal body, lengthening of the anterior vaginal wall, and increased size of the vaginal introitus with strain were associated with anatomic failure. Further studies are needed to provide additional insight into the mechanism by which these factors contribute to anatomic failure.

• #1 Uterine Prolapse: Stages, Symptoms, Treatment & Surgery

  https://my.clevelandclinic.org/health/diseases/16030-uterine-prolapse

  Uterine prolapse is a condition where the muscles and tissues around your uterus become weak. This causes your uterus to sag or drop down into your vagina. […] A prolapse occurs when your pelvic floor muscles are damaged or weakened to the point where they can no longer provide support. This causes your pelvic organs to drop into or out of your vagina. […] Your uterus is held in place within your pelvis by a group of muscles and ligaments (pelvic floor muscles). When these structures weaken, they become unable to hold your uterus in position and it begins to sag. Several factors can contribute to the weakening of the pelvic muscles, including: Loss of muscle tone as the result of menopause. […] Uterine prolapse can affect other organs in the pelvic area of your body (like your bladder and rectum).

• #1 Pathophysiology of Pelvic Organ Prolapse | IntechOpen

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

  Pelvic organ support is provided by interaction between the pelvic floor muscle, ligaments and its connective tissues. Failure of anatomical support may result in pelvic organ prolapse. […] To appropriately treat these entities, comprehension of the various theories of the pathophysiology of pelvic organ prolapse is of paramount importance. […] A better understanding of pathophysiology of muscular, collagen, and neuronal components of the pelvic organs and their support would provide an insight of site specific defects and its prevention. […] 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). […] With advancing age, incidence and prevalence of POP increases.

• #2 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.

• #2 FUNCTIONAL ANATOMY AND PATHOPHYSIOLOGY OF PELVIC ORGAN PROLAPSE | Abdominal Key

  https://abdominalkey.com/functional-anatomy-and-pathophysiology-of-pelvic-organ-prolapse/

  Pelvic organ prolapse is responsible for twice as many operations, yet its causes are largely unknown. […] Prolapse arises because of injuries and deterioration of the muscles, nerves, and connective tissues that support and control normal pelvic function. […] The pelvic organ support system is multifaceted and includes the endopelvic fascia, the perineal membrane, and the levator ani muscles, which are controlled by the central and peripheral nervous system. […] Damage to level I support can result in uterine or vaginal prolapse of the apical segment. […] Damage to the upper suspensory fibers of the paracolpium (cardinal and uterosacral ligaments) allows uterine or apical segment prolapse. […] The nature of uterine support can be understood when the cervix is pulled downward with a tenaculum during dilation and curettage. […] Although descriptions of uterine support often imply that the uterus is suspended by the cardinal/uterosacral complex, much like a light suspended by a wire from the ceiling, this is not the case.

• #2 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). […] 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. […] Normal pelvic support is primarily provided by the levator ani muscles and the connective tissue attachments of the vagina to the sidewalls and pelvis. […] 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.

• #2 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. […] 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. […] Pelvic organ prolapse (POP) is a common condition that is multifactorial in etiology. […] Adequate support of the vaginal apex has been recognized as an essential component of an adequate surgical repair for advanced prolapse.

• #2 Pelvic organ prolapse – a review

  https://www.racgp.org.au/afp/2015/july/pelvic-organ-prolapse-a-review

  Another explanation is impairment of the levator ani through pudendal nerve trauma; however, there is little evidence of neuropathy in women with prolapse. […] The largest potential hernial portal in the human body, the levator hiatus, is also the most critical soft tissue impediment to vaginal childbirth. […] The result is enlargement of the levator hiatus and an increased risk of FPOP, which may be difficult to treat. […] Avulsion can be diagnosed by palpation, which, together with prolapse quantification using the POP-Q system, is well within the scope of general practice. […] Primary prevention is feasible through modification of obstetric management. […] The main modifiable risk factor for pelvic floor trauma and later pelvic organ prolapse is forceps, whereas vacuum is not associated with increased risk.

• #2 Pathophysiology of Pelvic Organ Prolapse | IntechOpen

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

  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 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.

• #2 Role of Fibroblasts and Myofibroblasts on the Pathogenesis and Treatment of Pelvic Organ Prolapse

  https://www.mdpi.com/2218-273X/12/1/94

  Aging is directly correlated with the incidence of POP, as the circulating estrogen levels are drastically decreased in postmenopausal women. […] Abnormal repair of the injured tissue after the vaginal delivery may lead to changes in ECM in the pelvic floor, consequently affecting the mechanical endurance of the pelvic floor tissue. […] Changes in the ECM and collagen metabolism, such as the decreased amount of collagen, increased collagen break-down, or altered ECM remodeling and/or expression of structural proteins resulting from gen-mutations or decreased estrogen levels, may all increase the risk on POP. […] The differences in the vaginal connective tissue of the women with POP and no POP resemble the changes occurring in the tissue after injury. […] Without a doubt, fibroblasts and (myo)fibroblasts have a key role in the healing and remodeling processes either in the development or in the treatment of POP.

• #2 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

  Thus, understanding the molecular mechanisms of biomechanical and biochemical coupling in fibroblasts, which are the basic components of POP, is important for the prevention and treatment of POP. […] Fibroblasts produce extracellular matrix (ECM) and are the major cells in the pelvic floor. […] Current research indicates that dysfunction of ECM in vaginal wall and USL decreases biomechanics, which is a major factor in POP. […] The findings suggest a potential mechanism by which the excessive degradation of ECM components contributes to the development and progression of POP. […] Biomechanical forces, which are risk factors, disrupt the mechanical–chemical microenvironment of POP-HVFs, particularly ECM components and cell-ECM interactions, ultimately resulting in the differential responses of fibroblasts to exogenous mechanical stretching. […] These factors lead to an increase in ECM degradation and a decrease in collagen synthesis. […] Overall, these studies suggest that cell apoptosis is a key mechanism underlying POP development.

• #2 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

  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 strength of collagen, the main component of the body’s connective tissue, and specifically of the pelvic floor fascia and ligaments, is determined by genetic factors. […] The apparent influence of estrogen and SERM on the synthesis of estrogen receptors may explain the contradicting association between SERM and the incidence of POP, most likely by altering the ratio between alpha and beta estrogen receptors.

• #2 Single-cell transcriptome profiling of the vaginal wall in women with severe anterior vaginal prolapse | Nature Communications

  https://www.nature.com/articles/s41467-020-20358-y

  Anterior vaginal prolapse (AVP) is the most common form of pelvic organ prolapse (POP) and has deleterious effects on women’s health. […] We reveal aberrant gene expression in diverse cell types in AVP. Extracellular matrix (ECM) dysregulation and immune reactions involvement are identified in both non-immune and immune cell types. […] Several transcription factors associated with ECM and immune regulation are activated in AVP. […] We demonstrate the changes in both non-immune and immune cells in the etiology of POP. […] The cellular composition of the vaginal wall is complex, comprising primarily fibroblasts and smooth muscle cells (SMCs), which play important roles in the extracellular integrity and mechanical stretching of the anterior vaginal wall. […] The main constituents in vaginal connective tissues—collagen and elastin fibers—are altered and that an imbalance in matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) leads to dysregulation of extracellular matrix (ECM) metabolism, which in turn influences the architectural remodeling of the vaginal muscularis propria.

• #2 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. […] The cause of pelvic organ prolapse is multifactorial, but pregnancy is the most commonly associated risk factor. […] Additional risk factors for prolapse are listed in Table 1.

• #2 Pathophysiology of Pelvic Organ Prolapse | IntechOpen

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

  Pelvic organ support is provided by interaction between the pelvic floor muscle, ligaments and its connective tissues. Failure of anatomical support may result in pelvic organ prolapse. […] To appropriately treat these entities, comprehension of the various theories of the pathophysiology of pelvic organ prolapse is of paramount importance. […] A better understanding of pathophysiology of muscular, collagen, and neuronal components of the pelvic organs and their support would provide an insight of site specific defects and its prevention. […] 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). […] With advancing age, incidence and prevalence of POP increases.

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

  https://emedicine.medscape.com/article/264231-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.

• #2 Cellular senescence: A pathogenic mechanism of pelvic organ prolapse (Review)

  https://www.spandidos-publications.com/10.3892/mmr.2020.11339

  The main five hallmarks of POP associated with aging were reviewed primarily based on a previous review on the hallmarks of general aging. Genomic instability and imbalanced proteostasis are likely to be the primary triggers of aging-related prolapse. Mitochondrial dysfunction in the progression of senescence may consequentially become the integrated cause of POP. Cell senescence, one facet of the aging process, is a collective phenotype caused by a complex network of signaling pathways. Mechanisms causing fibroblast senescence, including gene instability, mitochondrial dysfunction and altered senescence-symbolized phenotype, provide a basis for senescence-related POP pathological mechanisms.

• #2 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

  The current understanding of the pelvic floor is based on the work of two modern anatomists: Peter Petros and John Delancey. These two researchers have studied the pelvic floor extensively and have incorporated in their studies advanced dynamic imaging techniques. […] According to the integral theory, POP and its related symptoms result from over-laxity of the vaginal connective tissue or its supporting ligaments.

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

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

  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. […] 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, MMP and TIMP functions are balanced in order to regulate ECM anabolism. […] It may be considered that the anabolism and catabolism of ECM are inseparable and intricate. Decreased anabolism and increased catabolism are key factors for the onset of POP.

• #2

  https://step2.medbullets.com/gynecology/121754/uterine-prolapse

  Uterine prolapse occurs when pelvic floor musculature is unable to provide adequate support […] ligaments can stretch and weaken over time […] most important in preventing prolapse […] Pathogenesis […] incomplete prolapse […] uterus drops part way down into the vagina […] creates a bulge […] complete prolapse […] uterus slips down and protrudes out of the vagina […] Kegel exercises […] mechanism […] strengthen pelvic floor musculature […] vaginal pessary […] mechanism […] rubber device that fits around the cervix to help hold the uterus in place […] hysterectomy […] mechanism […] removal of uterus […] sacrohysteropexy […] mechanism […] resuspension of the prolapsed uterus using a mesh sling.

• #2 Pelvic Organ Prolapse – StatPearls – NCBI Bookshelf

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

  The advantages of transvaginal approaches include shorter operative and recovery times, whereas the advantages of abdominal approaches provide more durable outcomes and decrease the risk of recurrence. […] In recent years, the procedure of choice has become the abdominal sacrocolpopexy, which either laparotomy, laparoscopy, or robotic-assisted can do. Since Lane’s initial delineation of the procedure in 1962, the procedure has undergone many modifications.

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

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

  Pelvic organ prolapse can be uncomfortable and affect your quality of life. Other than urinary and fecal incontinence, some of the other possible complications of a prolapse are: […] Surgery may be an option if your symptoms don’t improve with conservative treatments or if your provider believes surgery gives you the best quality of life moving forward. […] Reconstructive surgery repairs the weak parts of your pelvic floor and moves the organs back to their typical position.

• #2 Role of Fibroblasts and Myofibroblasts on the Pathogenesis and Treatment of Pelvic Organ Prolapse

  https://www.mdpi.com/2218-273X/12/1/94

  Therefore, vaginal fibroblasts might recognize the resulting POP-ECMs after an injury as scar tissues that need to be remodeled. […] Understanding the mechanisms of tissue repair and the involvement of fibroblast–(myo)fibroblast transition in the healing process can provide a rational basis for disease modeling and innovative solutions in vaginal reconstruction for POP.

• #3 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 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.

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

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

  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. […] 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, MMP and TIMP functions are balanced in order to regulate ECM anabolism. […] It may be considered that the anabolism and catabolism of ECM are inseparable and intricate. Decreased anabolism and increased catabolism are key factors for the onset of POP.

• #3 Single-cell transcriptome profiling of the vaginal wall in women with severe anterior vaginal prolapse | Nature Communications

  https://www.nature.com/articles/s41467-020-20358-y

  The number of upregulated genes was higher than the number of downregulated genes in all cell types except for epithelial cells, lymphatic endothelial cells, B cells, plasma B cells and mast cells. […] The enrichment of the term ECM organization and disassembly in most cell types suggested that diverse types of vaginal cells are widely involved in ECM dysregulation. […] The phenotypic function of smooth muscle cells might switch and play a vital role in collagen metabolism when prolapse occurs, consistent with previous studies reporting that smooth muscle cells undergo an aberrant switch from a contractile to a synthetic ECM phenotype and contribute to the distensibility and fragility of the prolapsed vaginal wall. […] Together, these results indicate that most cell types participate in ECM dysregulation and immune reaction disorder in the prolapsed vaginal wall during the prolapse process. […] We identified dysregulation of several important candidate transcription factors regulating DEGs and functions in POP.

• #3 Pathophysiology of Pelvic Organ Prolapse | IntechOpen

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

  The relative prevalence of POP increased by about 40% with every decade of life. […] 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. […] Changes in biomechanical properties of the vaginal wall have been studied in fibulin-5 knockout mice (Fbln5/) with and without prolapse. […] The causative links between childbirth and prolapse have shown by various epidemiological and observational cohort studies. […] 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.

• #3 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. […] 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. […] Pelvic organ prolapse (POP) is a common condition that is multifactorial in etiology. […] Adequate support of the vaginal apex has been recognized as an essential component of an adequate surgical repair for advanced prolapse.

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

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

  OS may cause increased oxidative modification of DNA, lipids and proteins, and induce mitochondrial apoptosis. […] 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. […] 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.

• #3

  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.

• #4 Uterine prolapse: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/001508.htm

  Uterine prolapse occurs when the womb (uterus) drops down and presses into the vaginal area. […] Muscles, ligaments, and other structures hold the uterus in the pelvis. If these tissues are weak or stretched, the uterus drops into the vaginal canal. This is called prolapse. […] Other things that can cause or lead to uterine prolapse include: Normal aging, Lack of estrogen after menopause, Conditions that put pressure on the pelvic muscles, such as chronic cough and obesity, Pelvic tumor (rare). […] Repeated straining to have a bowel movement due to long-term constipation can make the problem worse. […] Uterine prolapse is mild when the cervix drops into the lower part of the vagina. Uterine prolapse is moderate when the cervix drops out of the vaginal opening. […] There are some surgical procedures that can be done without removing the uterus, such as a sacrospinous fixation. This procedure involves using nearby ligaments to support the uterus.

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