Development Of Pelvic Organ Prolapse Research Articles

Quantification of senescence-associated secretory phenotype proteins in the vaginal secretions of pre- and postmenopausal women with and without prolapse.

Cellular senescence has been proposed as a pathophysiologic driver in the development of pelvic organ prolapse (POP), especially during aging. In this study, we aimed to determine if markers of cell senescence can be quantified from vaginal secretions collected from pre- and postmenopausal women with and without POP. Vaginal swabs were collected from 81 women in four groups: premenopausal with (pre-P) and without prolapse (pre-NP), and postmenopausal with (post-P) and without prolapse (post-NP). Multiplex immunoassays (MagPix) were then used to detect and quantify the presence of 10 SASP proteins in vaginal secretions. The total protein concentration of vaginal secretions differed significantly among the four groups (P = 0.003) with highest mean concentrations in pre-P [16, interquartile range (IQR) = 4.6, 38.3 μg/μL] and lowest mean concentrations in post-P (4.4, IQR = 2.6, 7 μg/μL). The normalized concentrations of several SASP markers differed significantly among groups, with the highest concentrations being seen in the post-P group, and the lowest concentrations being in the pre-NP group. Using these key markers, we then constructed receiver-operator curves to determine the relative sensitivity and specificity of these markers in predicting prolapse. In this study, we found that SASP proteins can be detected and quantified in vaginal secretions. Several of these markers were differentially expressed among the four groups studied, with the highest normalized concentrations of SASP markers found among postmenopausal women with prolapse. Overall, the data support the theory that senescence is associated with prolapse during aging but that other factors may be important in younger women who develop POP before menopause.

Correlation between postpartum pelvic floor dysfunction and vaginal microecological imbalance in late pregnancy.

Pelvic floor dysfunction (PFD) seriously affects women's physical and mental health. Pregnancy and childbirth are recognized as high-risk factors for PFD, and studies have shown that vaginal microenvironmental disorders can promote the development of pelvic organ prolapse. In this study, we intend to investigate whether the changes in vaginal microecology during pregnancy affect the pelvic floor function and participate in the development of postpartum PFD, and provide a basis for the prevention and treatment of PFD. A total of 358 full-term mothers who delivered in Third Xiangya Hospital, Central South University from November 2019 to April 2020 were selected and underwent review 6 to 8 weeks after delivery. The pelvic floor structures were examined using pelvic floor ultrasound, and ultrasound values were measured at rest and at maximum Valsalva maneuver. One hundred and seventy women with PFD were assigned in a PFD group, and 188 women without PFD were assigned in a control group. The clinical data of all mothers were collected, and the clinical data and the results of microecological testing for vaginal secretions after 36 weeks of gestation and before delivery were compared between the 2 groups. The correlation of PFD with leucorrhoea cleanliness, lactobacillus level, bacterial vaginosis (BV), and vulvovaginal candidiasis (VVC) was analyzed, and logistic regression analysis was used to screen for independent risk factors for PFD. The incidences of VVC, BV, Lactobacillus vaginalis deficiency, and leucorrhoea cleanliness ≥III° were all higher in the PFD group than those in the control group (P<0.05). Among them, leukocyte cleanliness ≥III°and lack of Lactobacilli in the vagina were independent risk factors for the development of PFD, while VVC and BV were not independent risk factors for the development of PFD. Postpartum PFD is related to vaginal microecological imbalance in late pregnancy, among which Lactobacillus vaginalis deficiency and leucorrhoea cleanliness ≥III° are independent risk factors for the occurrence of PFD. Therefore, pregnant women with Lactobacillus vaginalis deficiency and leucorrhoea cleanliness ≥III° in late pregnancy should pay attention to the occurrence of postpartum PFD, and early diagnosis and effective intervention of postpartum PFD should be enhanced.

Intrapartum risk factors associated with pelvic organ prolapse at 6 months postpartum

Pregnancy and childbirth are known risk factors associated with the development of pelvic organ prolapse; specific intrapartum risk factors are not well characterized. This study aimed to determine intrapartum factors associated with increased risk of pelvic organ prolapse identified after delivery. A planned secondary analysis of a multicenter randomized clinical trial of delayed vs immediate pushing among nulliparous women at ≥37 weeks of gestation in labor with neuraxial analgesia was conducted at 6 academic and community hospitals in the United States. Intrapartum characteristics were identified, and Pelvic Organ Prolapse Quantification assessments at 6 weeks and 6 months after delivery were performed. The primary outcome was pelvic organ prolapse, defined as stage 2 or greater prolapse using the Pelvic Organ Prolapse Quantification assessment at 6 months. Multivariable logistic regression was used to refine risk estimates while adjusting for randomization group, macrosomia, and maternal age. Among the 941 women participating in the pelvic floor follow-up, 793 women had Pelvic Organ Prolapse Quantification assessments at 6 weeks with 91 of 793 women (11.5%) demonstrating stage 2 or greater prolapse. Of the 728 women followed up at 6 months, stage 2 or greater prolapse was identified in 58 of 728 women (8.0%). Prostaglandin use for induction of labor was associated with an increased risk at 6 months (adjusted odds ratio, 2.15; 95% confidence interval, 1.18-3.91; P<.01). The length and type (spontaneous vs induced) of the first stage of labor were not significantly associated with stage 2 or greater prolapse. Moreover, increased length of the second stage of labor and duration of pushing were not associated with stage 2 or greater prolapse. After adjusting for confounding factors, cesarean delivery was protective of pelvic organ prolapse at 6 months (adjusted odds ratio, 0.12; 95% confidence interval, 0.02-0.90). The management of the first and second stages of labor, including time length, was not associated with stage 2 or greater prolapse at 6 months. The findings that prostaglandin exposure was associated with increased risk likely were not directly affecting the risk of prolapse but may be surrogates for other labor features that deserve exploration. Cesarean delivery was associated with protection from stage 2 or greater pelvic organ prolapse at 6 months, consistent with previous literature.

Modeling permanent deformation during low-cycle fatigue: Application to the pelvic floor muscles during labor

Low cycle fatigue (between two to hundreds of cycles) is associated with large permanent strains and the development of microdamage that can start as soon as the first cycle. It has been identified as a possible damage mechanism in the anterior cruciate ligament and recently was evaluated as a potential damage mechanism at the origin of the pubovisceral muscle (a pelvic floor muscle) near the end of labor. The purpose of this work is to provide a numerical framework that incorporates the effects of permanent deformation due to low-cycle fatigue. Based on experimental evidence, we hypothesize that the microdamage accumulation due to repetitive sub-maximal loading continuously induces macroscopic permanent deformations that adversely affect the tissue mechanical properties and thereby cause stress softening. The constitutive model is suitable for 3D finite element analysis. The model was first tested against simple numerical examples, where quadratic convergence and objectivity were verified. Next, we applied the approach to a human vaginal delivery, employing a transversely isotropic visco-hyperelastic baseline model. It demonstrated the potential of this numerical framework for simulating permanent deformation in pelvic floor muscles during birth. With robust experimental data, this can be an important tool to analyze the obstetrical risk factors for the pelvic floor permanent deformation associated with the development of pelvic organ prolapse later in life.

Cervical insufficiency a prologue for future pelvic organ prolapse?

Preliminary evidence suggests that women with cervical oss insufficiency may have an increased risk to develop pelvic organ prolapse later in life, suggesting a common underlying collagen-oriented mechanism. The objective of this study was to determine the association between cervical oss insufficiency and the subsequent development of pelvic organ prolapse. A matched, case-control study, including women who delivered at the Soroka University Medical Center. Cases were women diagnosed or treated with pelvic organ prolapse (n = 1463), and controls were a representative sample of women of the same age group without pelvic organ prolapse (n = 5637). The association between pelvic organ prolapse and prior preterm birth was tested. Univariate analysis was performed using a conditional logistic regression to assess the association between preterm labor and pelvic organ prolapse. Statistically and clinically significant variables in the univariate analysis were included in the multivariable regression. The rate of spontaneous preterm birth did not differ between the study groups [pelvic organ prolapse - 4.0% (59/1463) vs. non- pelvic organ prolapse - 4.9% (276/5637), p = 0.16]. The median number of preterm births was higher among women without pelvic organ prolapse (controls) than in those with pelvic organ prolapse (cases) (p = 0.004). Among those who delivered preterm, the individual proportion of preterm deliveries was higher among the controls' group (p = 0.03). Similarly, the rate of cesarean deliveries was also higher among the controls group (p = 0.003). The rate of small for gestational age neonates was higher in the controls group (p = 0.0007), while that of large for gestational age neonates was higher in the case group (p = 0.02). In the univariate analysis, birthweight, vaginal delivery, and prior surgery were associated with subsequent development of pelvic organ prolapse. The multivariable analysis exhibited the same association- having birthweight, vaginal delivery, and all types of prior surgery independently associated with subsequent development of pelvic organ prolapse. Obstetrics characteristics associated with pelvic organ prolapse included vaginal delivery and birthweight along with non-obstetrical factors such as prior surgery. There was no association between preterm birth and subsequent development of pelvic organ prolapse. Our findings suggest that the effort during labor at term required for the delivery of appropriate for gestational age or large for gestational age newborns affects the pelvic floor and is a major contributor for the subsequent development of pelvic organ prolapse.

Полиэтиологичность патогенеза пролапса тазовых органов у женщин. Современные представления о проблеме

This review presents the analysis of literature which reveals the role of various factors contributing to the development of pelvic organ prolapse in women. The role and significance of factors leading to elevated intra-abdominal pressure, including obesity, are discussed. The effect of natural childbirth on the structure and function of pelvic floor is assessed. A current perspective on the influence of estrogen levels on the structure and properties of pelvic connective tissue in women is presented. The issue of metabolic and structural disorders of collagen in the development of pelvic organ prolapse as well as the role and significance of hereditary connective tissue disorders in the genesis of this disease are considered separately. The connection between pelvic surgeries such as hysterectomy and the subsequent development of pelvic organ prolapse is traced and analyzed. Particular attention is paid to the analysis of the effectiveness of surgical treatment for pelvic organ prolapse, also data on the use of mesh materials is provided, and the possibility of increasing the efficacy of surgical treatment by improving surgical techniques and using promising synthetic materials with stem cells is discussed. Key words: pelvic organ prolapse, hereditary connective tissue disorders, recurrence, pelvic floor, birth-related perineal trauma, risk factors for pelvic organ prolapse, surgical correction

The polymorphisms of extracellular matrix-remodeling genes are associated with pelvic organ prolapse

Introduction and hypothesisExtracellular matrix (ECM) synthesis and metabolism abnormalities may influence the pelvic supporting system and lead to the occurrence and development of pelvic organ prolapse (POP). Genetic polymorphisms of such related genes have been increasingly studied. This study aims to explore the association between the single-nucleotide polymorphisms (SNPs) of genes encoding ECM processing enzymes (a disintegrin and metalloproteinase with thrombospondin motifs [ADAMTSs]), ECM degrading enzymes (matrix metalloproteinases [MMPs]) and their tissue inhibitors of metalloproteinase (TIMPs), and POP.MethodsWe conducted an association study including 48 women with POP at stages III and IV and 48 women without prolapse in Chinese groups. SNPs were identified using the target region sequencing technique. We performed Fisher’s exact tests to assess the association between SNPs and POP in the unadjusted model and logistic regression analysis in the adjusted model, adjusting for delivery and pregnancy.ResultsThere was a significant association between TIMP2 SNP rs2277698 (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.16–0.82; P = 0.015), ADAMTS13 SNP rs149586801 (OR, 0.18; 95% CI, 0.05–0.69; P = 0.012), and ADAMTS1 SNPs rs370850 and rs422803 (OR, 3.71; 95% CI, 1.35–10.15; P = 0.011 for both), rs402007, rs428785, rs434857, and rs445784 (OR, 2.18; 95% CI, 1.05–4.56; P = 0.038 for the four), and POP in the adjusted model.ConclusionTIMP2, ADAMTS13, and ADAMTS1 might be candidate genes for POP. Our results provide preliminarily new evidence for future investigation of these genes in the pathophysiology of POP.

Doğum şekli ve paritenin pelvik organ prolapsusu ve üriner inkontinans gelişimi üzerine etkisi

Aim: To investigate the effect of delivery mode and parity number on development of pelvic organ prolapse (POP) and urinary incontinence (UI).&#x0D; Materials and methods: 1500 women who had undergone surgery for POP and UI between 2007-2012 were retrospectively evaluated. After exclusion criteria, 875 women were included. 353 women with history of POP surgery were compared with 129 controls who had no POP and 201 patients with history of anti-incontinence surgery were compared with 192 controls who had no such surgery. Multiple effect of possible factors on the development of POP and UI was determined by logistic regression.&#x0D; Results: The characteristics of POP group and the controls, as well as anti incontinence surgery group and controls were similar, except parity number. The risk of having a POP surgery was higher with increasing number of parity. The highest risk was found in women with a history of 5 and more deliveries. For UI, multiparity seemed as a risk factor, however the risk of undergoing incontinence surgery did not increase with increasing number of parity. Delivery mode was not a risk factor for either POP or anti-incontinence group.&#x0D; Conclusion: The risk of POP increases with increasing number of parity, and also multiparity is a risk factor for UI. Women planning more than one delivery should be informed about this concern. Since the impact of delivery mode has not been shown clearly, we believe the incidence of pelvic floor dysfunction can be decreased with proper obstetric

Intrapartum Risk Factors for Pelvic Organ Prolapse Postpartum

Pregnancy and childbirth are thought to be significant risk factors associated with the development of pelvic organ prolapse; specific intrapartum risk factors are not well characterized. The objective was to determine intrapartum factors associated with increased risk of pelvic organ prolapse identified postpartum.

Modern aspects of the fascial structure of the pelvic floor (literature review)

The pelvic floor fascia in women has attracted the attention of obstetricians-gynecologists, proctologists and rehabilitologists due to their possible role in the development of pelvic organ prolapse and the appearance of pelvic pain. The development and improvement of new surgical techniques entails a comprehensive study of previously known approaches. For instance, regarding fascial tissues, studying the actual use of fascial flaps in plastic and reconstructive surgeries is of particular interest. This necessitates an accurate definition of and knowledge about structure of the fascia and their variations. In addition, knowledge of the fascial structure of surgical methods for treating prolapse, such as the installation of mesh prostheses in the reconstruction of the pelvic floor in the absence of alternative methods of correction. Primarily postoperative pain, a more in-depth study of the fascial anatomy of the pelvic floor can help reduce these adverse outcomes. The morphological and physiological characteristics of the perineal fascia presented in the teaching materials and teaching aids are not descriptive in nature and are far from the descriptive practice of obstetricians-gynecologists in the selection of methods for surgical correction of genital prolapse. This work is a literature review compiled from the sources of the electronic national bibliographic database of scientific citation of the Russian Science Citation Index and the English-language text database of medical and biological publications PubMed, created by the National Center for Biotechnological Information of the USA. To search for data, such key queries as fascia, pelvic floor, pelvic floor anatomy, genitourinary diaphragm, chronic pelvic pain were used, both individually and collectively.

Clinical and anamnestic and biological candidates for participation in the mechanisms of genital prolapse formation in women

Introduction.The article presents an overview of the results of modern evidence-based scientific research on the mechanisms of formation of genital prolapse as one of the fundamental causes of pelvic floor muscle insufficiency in women. A systematic analysis of the current literature data on the involvement of clinical, anamnestic and pathogenetic motives in the development of pelvic organ prolapse in women was carried out.Objective:to expand the understanding of the role of anamnestic and biological factors in the pathogenesis of genital prolapse in women.Material and method.The review includes the scale of publications of domestic and foreign authors included in the PubMed database on this topic with a search depth of 20 years. The criteria for inclusion of articles for the system analysis were articles corresponding to the topic chosen for the study of the problem of gynecology, namely, the pathogenesis of genital prolapse in women with a search depth of twenty years. The criteria for exclusion from the study are the age of published scientific works, exceeding a twenty-year period, and inconsistency with the chosen top.Results.The conducted analysis demonstrates the fundamental role of epigenetic factors and molecular genetic predisposition in patients in the progression of genital prolapse which makes it possible to develop personalized prediction and prevention of pelvic floor dysfunction in women, prevention of social burnout.Conclusion.Further study of the mechanisms of formation, determination of the most significant molecular and genetic polymorphisms that increase the risk of pelvic organ prolapse in women, is a promising vector of scientific research. These studies will help to form a pathophysiological basis that allow for a thorough examination to identify a predisposition to the development of a severe disease long before its occurrence.

The state of bone mineral density in the prolapse of the pelvic organs

Background. Plausible predictions of future mortality and disability are useful aids in making decisions about priorities for medical research. Recent advances in medicine have led to the fact that some countries, such as Japan, have the highest life expectancy in the world. Osteoporotic fractures make a significant contribution to the development of morbidity and mortality in the aging population. Despite an active study of the mechanisms of the development of pelvic organ prolapse and disorders of bone mineral density separately, the general background of these diseases has previously been little studied.&#x0D; Aim. To study bone density according to densitometry data in peri- and postmenopausal women.&#x0D; Materials and methods. To carry out this study, 2 groups of women were formed. The first (experimental) group included 76 women admitted for routine surgical treatment of genital prolapse, the second group (control) 68 women without clinical manifestations of pelvic floor descent, who underwent a medical examination by a gynecologist on an outpatient basis.&#x0D; Results. Analysis of extragenital diseases in women included in the study showed a high prevalence in the experimental group of hypertension (p=0.028), osteochondrosis (p=0.001), scoliosis (p=0.028), hemorrhoids (p=0.013). Also, women in this group more often noted stretch marks on the skin (p=0.002) and were more often operated on for other diseases (p=0.043), which indicates the association of genital prolapse with undifferentiated connective tissue dysplasia and hypertension. The diagnosed severe osteoporosis (according to 1 or more densitometry indicators, where the T-score is less than -2.5) had a direct correlation with the duration of menopause. For a detailed analysis of the factors influencing severe osteoporosis in peri- and postmenopausal women, logistic regression analysis and ROC analysis were performed. The independent variable was the presence of severe osteoporosis, and the dependent variables were: stage according to POP-Q, the presence of hypertension, the presence of diabetes mellitus in history.&#x0D; Conclusion. This study confirms the presence of a comorbidity decrease in bone density according to densitometry and the presence of hypertension (p=0.028) and genital prolapse. According to the ROC analysis, an increase in the stage of genital prolapse according to the POP-Q classification increases the risk of developing severe osteoporosis.

The Role of Collagen Genetic Discrepancies in Development of Pelvic Organ Prolapse in Women: A Study with Negative Results

Pelvic organ prolapse has a mixed aetiology – hereditary and acquired. During last decade, the role of genetics in POP becomes profoundly obvious. women with a family history of prolapse are at an increased risk of prolapse refractory to treatment. Careful literature review from the past studies reveals that several genetic mutations have been shown to correlate with increased prolapse susceptibility. These mutations can result in disordered collagen metabolism, which weaken the fascial support of the pelvic organs. This prompt us to undertake the above study, look more into genetic discrepancies and pelvic organ prolapse contemporary studies relate to this topic shows that Collagen is playing a major role in pelvic floor supportive structures. However role of single nucleotide polymorphism (SNP) of the COL1A1 or COL3A1 or COL18A1 genes remain controversial relate to pelvic organ prolapse. Some studies and meta-analysis found a strict correlation between these genetic defects and POP.

The Role of Collagen Genetic Discrepancies in Development of Pelvic Organ Prolapse in Women: A Study with Negative Results

Pelvic organ prolapse has a mixed aetiology – hereditary and acquired. During last decade, the role of genetics in POP becomes profoundly obvious. women with a family history of prolapse are at an increased risk of prolapse refractory to treatment. Careful literature review from the past studies reveals that several genetic mutations have been shown to correlate with increased prolapse susceptibility. These mutations can result in disordered collagen metabolism, which weaken the fascial support of the pelvic organs. This prompt us to undertake the above study, look more into genetic discrepancies and pelvic organ prolapse contemporary studies relate to this topic shows that Collagen is playing a major role in pelvic floor supportive structures. However role of single nucleotide polymorphism (SNP) of the COL1A1 or COL3A1 or COL18A1 genes remain controversial relate to pelvic organ prolapse. Some studies and meta-analysis found a strict correlation between these genetic defects and POP.

Artificial neural network in prediction of pelvic organ prolapse

The aim of this study was to assess the possibility of using an artificial neural network in predicting pelvic organ prolapse. 180 patients were selected from the urological database, of which 62 had pelvic organ prolapse, in 118 cases prolapse was not detected. Data analysis was carried out with the use of the artificial neural network (ANN). As a result, the most important risk factors or predictors for the development of pelvic organ prolapse include the number of births, the number of pregnancies, chronic obstructive pulmonary disease, prolapse of the heart valves, as well as accessory chords, urinary incontinence before/after childbirth, BMI. Artificial neuron network can potentially be useful in decision-making on the development of preventive measures aimed at the prophylaxis of pelvic organ prolapse.

Altered mechanics of vaginal smooth muscle cells due to the lysyl oxidase-like1 knockout

The remodeling mechanisms that cause connective tissue of the vaginal wall, consisting mostly of smooth muscle, to weaken after vaginal delivery are not fully understood. Abnormal remodeling after delivery can contribute to development of pelvic organ prolapse and other pelvic floor disorders.The present study used vaginal smooth muscle cells (vSMCs) isolated from knockout mice lacking the expression of the lysyl oxidase-like1 (LOXL1) enzyme, a well-characterized animal model for pelvic organ prolapse. We tested if vaginal smooth muscle cells from LOXL1 knockout mice have altered mechanics including stiffness and surface adhesion.Using atomic force microscopy, we performed nanoindentations on both isolated and confluent cells to evaluate the effect of LOXL1 knockout on in vitro cultures of vSMCs cells from nulliparous mice. The results show that LOXL1 knockout vSMCs have increased stiffness in pre-confluent but decreased stiffness in confluent cultures (p* < 0.05) and significant decreased surface adhesion in pre-confluent cultures (p* < 0.05). This study provides evidence that the weakening of vaginal connective tissue in the absense of LOXL1 changes the mechanical properties of the vSMCs. Statement of significancePelvic organ prolapse is a common condition affecting millions of women worldwide, which significantly impacts their quality of life. Alterations in vaginal and pelvic floor mechanical properties can change their ability to support the pelvic organs. This study provides evidence of altered stiffness of vaginal smooth muscle cells from mice resembling pelvic organ prolapse. The results from this study set a foundation to develop pathophysiology–driven therapies focused on the interplay between smooth muscle mechanics and extracellular matrix remodeling.

Evaluation of implant-associated complications after mesh-implants setting in pelvic floor reconstruction

Relevance. According to world data, nowadays prevalence of pelvic floor dysfunction and pelvic organ prolapsed reaches 28%. Most specialists relate pregnancy and delivery to main factors of pelvic prolapse development. Due to lifespan growth frequency of pelvic organ prolapse development increases. According to FDA data annually in the world is made more than 100 000 surgeries with synthetic implants, herewith heavy complications occur in 3.4% and mild complications occur in 14.8% of all cases. About 58% of surgeries are made to women under the age of 60, 13% of patients needs re-intervention during next 5 years. It should be noted that in cases of relapse more than 30% of women need re-intervention. Aim. Evaluate implant-associated complications after mesh-implants setting. Materials and methods. We have made retrospective analysis of mesh-implant use in 458 patients with pelvic organ prolapse in 2018-2018 yy. on the base of Bashkir State Medical University clinic. In order to assess quality of life after mesh-implant setting, we used the following questionnaires: Incontinence Questionnaire Short Form (ICIQ-SF), and also Female Sexual Function Index (FSFI). In order to assess blood microcirculation indices after surgery, we used laser Doppler flowmetry evaluation from anterior vaginal wall. Results. All in all, there were revealed 13 (2.84%) implant-associated complications. In 4 patients ICIQ-SF points were from 3 to 15, which indicates manifestation of urgent urine incontinence signs. According to FSFI questionnaire, sexually active women have 31.5 points. Basic factor, which provokes pelvic floor muscles dysfunction is delivery. Besides, in group of women of reproductive age, pelvic floor muscles dysfunction (PFMD) is associated with the presence of concomitant gynecologic diseases (uterine myoma, endometriosis, ovarian tumors). In the group of women older than 45 years with the presence of somatic pathology - obesity and impaired blood circulation. According to LDF data from anterior vaginal wall women with PFMD have low blood circulation indices, herewith the lowest indices are registered in the group of women older than 45 years.

Longitudinal Changes in the Genital Hiatus Preceding the Development of Pelvic Organ Prolapse

We aimed to explore relationships between changes in genital hiatus (GH) and development of pelvic organ prolapse using data from the Mothers’ Outcomes After Delivery (MOAD) Study, a Baltimore, Maryland, cohort study of parous women who underwent annual assessments during 2008–2018. Prolapse was defined as any vaginal segment protrusion beyond the hymen or reported prolapse surgery. For each case, 5 controls (matched on birth type and interval from first delivery to study enrollment) were selected using incidence sampling methods. We used a mixed model whose fixed effects described the initial size and slope of the GH as a function of prolapse status (case vs. control) and with nested (women within matched sets) random effects. Among 1,198 women followed for 1.0–7.3 years, 153 (13%) developed prolapse; 754 controls were matched to those women, yielding 3,664 visits for analysis. GH was 20% larger among the cases at enrollment (3.16 cm in cases vs. 2.62 cm in controls; P < 0.001), and the mean rate of increase in the size of the GH was more than 3 times greater (0.56 cm per 5-year period vs. 0.15 cm per 5-year period in controls; P < 0.001). Thus, to identify women at highest risk for developing prolapse, health-care providers could evaluate not simply the size of the GH but also changes in the GH over time.

Mitofusin2 regulates the proliferation and function of fibroblasts: The possible mechanisms underlying pelvic organ prolapse development.

The present study aimed to investigate the effects of Mitofusin2 (Mfn2) on the proliferation of human uterosacral ligament fibroblasts and on the expression of procollagen. We also aimed to identify the possible signal transduction pathway involved in the development of pelvic organ prolapse (POP). For this purpose, uterosacral ligaments were harvested from POP and non‑pelvic organ prolapse (NPOP) patients for fibroblast culture. Cellular proliferation and the cell cycle were assessed following transduction with lentiviral vectors for the overexpression and suppression of Mfn2. The expression levels of the proteins Mfn2, procollagens, phosphoprotein 21 wild‑type p53 activating fragment (p21Waf1), cyclin‑dependent kinase 2 (CDK2), extracellular signal‑regulated kinase1/2 (ERK1/2) and rapidly accelerated fibrosarcoma‑1 (Raf‑1) were examined. Overexpression of Mfn2 resulted in the decreased proliferation of cells and the induction of G0/G1 phase arrest. Concomitantly, the relative expression levels of procollagen proteins, CDK2 and the phosphorylation levels of ERK1/2 and Raf‑1 proteins were notably decreased, while the levels of the p21waf1 protein were increased in the Mfn2 overexpressing group. Opposing results were reported cells following Mfn2 silencing via RNA interference. The results of the present study indicated that the cell cycle of the fibroblasts, their cellular proliferation and the levels of the procollagen proteins could be inhibited via the Ras‑Raf‑ERK axis as a result of the increased levels of Mfn2 during the development of POP.

Changes in the PGC-1α and mtDNA copy number may play a role in the development of pelvic organ prolapse in pre-menopausal patients

ObjectiveThe alternations of mtDNA may play an important role in the molecular pathogenesis and process of Pelvic Organ Prolapse (POP) formation in both pre-menopausal and post-menopausal women. The aim of the present study is to analyze the association between the mitochondrial biogenesis gene and development of POP in the uterosacral ligaments (UL) of pre-menopausal women. Materials and methodsSeventy one pre-menopausal women, all below 52 years of age, were enrolled in this study. UL biopsies were obtained from uterine specimens taken from 33 women with POP (n = 33, study group) and 38 myoma patients without POP (n = 38, control group). Quantitative Real-Time PCR was performed to measure mitochondrial DNA (mtDNA) copy number and mtDNA4977. Western blotting and immunohistochemistry were used to assess the protein expression of PGC-1α, TFAM, NRF-1 and NRF-2. Statistical analysis was performed using SPSS statistical software and the Mann–Whitney U test, and the continuous variables were analyzed using the Student's t-test in demographic data. ResultsThere were no significant differences in the patient demographics between the two groups (p > 0.05). The mtDNA copy number in the UL of pre-menopausal patients with prolapse was significantly higher than that in the no prolapse group (p = 0.008). There were no significant differences between the mtDNA4977 of the POP and non-POP groups, but a significantly higher expression of PGC-1α in the POP group compared to the non-POP group (1.59 ± 1.30 v.s. 0.66 ± 0.53; p = 0.036). The expression of TFAM in the POP group was higher than in the non-POP group). There was no significant difference in the TFAM(p = 0.377), NRF-1 and NRF-2 expression between the POP and non-POP groups (p = 0.647; p = 0.682). ConclusionsChanges in the PGC-1α and mtDNA copy number may play a role in the development of Pelvic Organ Prolapse in pre-menopausal patients.