The rs2018736 fibulin-5 polymorphism as a determinant for pelvic organ prolapse: a case-control study.

OBJECTIVE: Fibulin-5 is a connective tissue component and may play a role in pelvic organ prolapse (POP) pathogenesis. This study aimed to verify the association of the rs2018736 polymorphism of the fibulin-5 gene with POP in postmenopausal Brazilian women, and to determine the risk factors for POP. METHOD: This observational, cross-sectional, case-control study assessed postmenopausal women with advanced POP (stages III and IV) and control women (stages 0 and I) by examination and peripheral blood sample collection. DNA sequences were analyzed by real-time reverse-transcriptase polymerase chain reaction. A logistic regression model was used with p < 0.05 for significance. RESULTS: A total of 565 participants were evaluated (325 POP and 240 control). The homozygous C allele of rs2018736 (CC) was protective against POP (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.26-0.91). Age (OR 1.09, 95% CI 1.05-1.13), number of pregnancies (OR 1.14, 95% CI 1.01-1.28), vaginal delivery (OR 5.32, 95% CI 2.58-11.01), forceps delivery (OR 3.34, 95% CI 1.72-6.47), weight of newborn (OR 1.0007, 95% CI 1.0002-1.0011), family history of POP (OR 2.35, 95% CI 1.24-4.44), hypertension (OR 1.74, 95% CI 1.01-3.00) and diabetes (OR 2.19, 95% CI 1.07-4.48)] were independent predictors for POP; cesarean (OR 0.02, 95% CI 0.005-0.09) was protective. CONCLUSION: The rs2018736-CC genotype of the fibulin-5 gene has a protective role against POP.

Association between the rs1036819 polymorphism of the ZFAT gene and pelvic organ prolapse: a case-control study.

INTRODUCTION AND HYPOTHESIS: The identification of risk factors for pelvic organ prolapse (POP) would contribute to planning prevention strategies. This study tests the hypothesis that the rs1036819 polymorphism in the ZFAT gene is associated with POP and investigates other risk factors for prolapse development. METHODS: A case-control study was carried out including 826 postmenopausal women divided into POP cases (stages III and IV) and controls (stages 0 and I), assessed by anamnesis, examination, and peripheral blood samples. DNA was extracted from blood and genotyped by real-time RT-PCR. We used logistic regression models for the association analyses of variables, with p < 0.05 for significance. RESULTS: Five hundred and sixty-eight women were evaluated (315 POP and 253 controls). The minor allele C was found in 19.3% of our sample and the genotype frequencies of AA, AC, and CC were similar in both groups. Age (OR 1.09, 95% CI 1.06-1.13), number of pregnancies (OR 1.23, 95% CI 1.08-1.41), history of one vaginal delivery (OR 3.39, 95% CI 1.38-8.33) or two or more (OR 2.51, 95% CI 1.04-6.07), weight of the largest newborn (OR 1.0001, 95% CI 1-1.001), and family history of POP (OR 2.27, 95% CI 1.24-4.13) were independent risk factors for POP, whereas one cesarean section (OR 0.48, 95% CI 0.27-0.88) or two or more (OR 0.14, 95% CI 0.05-0.38) were protective. CONCLUSIONS: No association was detected between the rs1036819 polymorphism of the ZFAT gene and advanced POP. Age, number of pregnancies, at least one vaginal delivery, weight of the newborn, and POP family history were independent risk factors for POP.

Mouse Knockout Models for Pelvic Organ Prolapse: a Systematic Review.

INTRODUCTION AND HYPOTHESIS: Mouse knockout (KO) models of pelvic organ prolapse (POP) have contributed mechanistic evidence for the role of connective tissue defects, specifically impaired elastic matrix remodeling. Our objective was to summarize what mouse KO models for POP are available and what have we learned from these mouse models about the pathophysiological mechanisms of POP development. METHODS: We conducted a systematic review and reported narrative findings according to PRISMA guidelines. Two independent reviewers searched PubMed, Scopus and Embase for relevant manuscripts and conference abstracts for the time frame of January 1, 2000, to March 31, 2021. Conference abstracts were limited to the past 5 years. RESULTS: The search strategy resulted in 294 total titles. We ultimately included 25 articles and an additional 11 conference abstracts. Five KO models have been studied: Loxl1, Fbln5, Fbln3, Hoxa11 and Upii-sv40t. Loxl1 and Fbln5 KO models have provided the most reliable and predictable POP phenotype. Loxl1 KO mice develop POP primarily from failure to heal after giving birth, whereas Fbln5 KO mice develop POP with aging. These mouse KO models have been used for a wide variety of investigations including genetic pathways involved in development of POP, biomechanical properties of the pelvic floor, elastic fiber deposition, POP therapies and the pathophysiology associated with mesh complications. CONCLUSIONS: Mouse KO models have proved to be a valuable tool in the study of specific genes and their role in the development and progression of POP. They may be useful to study POP treatments and POP complications.

Long-term effects of muscle-derived stem cell therapy on the regeneration of the urethra of female rats.

INTRODUCTION AND HYPOTHESIS: The aim was to analyze the long-term effects of muscle-derived stem cells (MDSCs) therapy in traumatized urethras of female rats regarding messenger ribonucleic acid (mRNA) expression of collagens 1 and 3, Ngf and Ki67; and the mRNA and protein expression of Myh11 and Myh2. METHODS: Muscle-derived stem cells were injected into the tail vein of rats 3 days after trauma by vaginal distention. Urethras were analyzed from 30 animals divided into three groups: control without injury or treatment, trauma (30 days post-injury), and MDSC (30 days post-injury who received MDSC therapy). Real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed. The Kruskal-Wallis and ANOVA tests were used with p < 0.05 indicating significance. RESULTS: We detected increased Myh11 and Myh2 mRNA expression in the trauma group compared with the control group (p = 0.03 and p = 0.04 respectively). Ki67 and Col1a1 genes were overexpressed in the MDSC group compared with both the trauma (p = 0.02 and p = 0.008 respectively) and the control group (p = 0.01 and p = 0.03 respectively). Col3a1 gene was upregulated in the MDSC compared with the control group (p = 0.03). Ngf mRNA level was lower in the MDSC group than in the trauma group (p = 0.002). Myh11, Myh2, and Desmin proteins were overexpressed in the MDSC compared with the trauma group (1.5-fold, p = 0.01; 1.5-fold, p = 0.04; 1.3-fold, p = 0.01 respectively). CONCLUSIONS: Muscle-derived stem cell therapy may have had long-term structural and molecular effects on the injured urethra of female rats, particularly on markers of cell proliferation, neural growth factor, extracellular matrix, and muscle content. This study suggests that MDSC therapy acted mainly to produce urethral sphincter regeneration marked by increased immunohistochemical expression of the proteins desmin, smooth muscle Myh11, and skeletal muscle Myh2.

Electrotherapy for urethral modulation: Are extracellular matrix molecules and growth factors potential targets?

AIMS: To evaluate the expression of genes and proteins involved in the urethral components: vessels, nerves, and extracellular matrix, in female rats after trauma by vaginal distension (VD) and after electrical stimulation therapy (electrotherapy). METHODS: We analyzed the urethras of three groups of 18 female rats 30 days posttrauma by VD: control (no interventions); trauma (animals that had VD); and electrotherapy group (those that had VD and were treated with electrical stimulation). We compared the expression of vascular endothelial growth factor (VEGF), nerve growth factor (NGF), collagen types I and III (COL1a1 and COL3a1), and lysyl-oxidase like 1 (LOXL1) among the groups. Real-time reverse transcription-polymerase chain reaction, Western blot, and immunohistochemistry were used for molecule quantification. We used the Kruskal-Wallis test and analysis of variance for statistical analyses with p < 0.05 for significance. RESULTS: The COL1a1 gene expression was higher in the electrotherapy group than the trauma group (p = 0.036). COL3a1, VEGF, NGF, LOXL1 messenger RNA (mRNA) expression did not differ among the groups (p ≥ 0.05). COL1a1, COL3a1, VEGF, NGF, LOXL1 protein levels did not significantly differ among the groups (p ≥ 0.05) in Western blot analysis or immunohistochemistry assays. CONCLUSIONS: Electrotherapy caused a long-term increase in the COL1a1 mRNA level but did not change COL1a1 protein expression or VEGF, NGF, COL3a1, and LOXL1 genes and proteins in the urethras of rats after trauma by VD.

Collagen I and collagen III polymorphisms in women with pelvic organ prolapse.

AIMS: Verify the presence of the single nucleotide polymorphisms rs1800012 of the collagen I (COL1A1) and rs1800255 of the collagen III (COL3A1) genes and their association with pelvic organ prolapse (POP) in Brazilian women and to determine risk factors for POP. METHODS: We assessed 826 postmenopausal women divided into POP (stages III and IV) and control groups (stages 0 and I) by examination and peripheral blood sample collection. DNA sequences of interest were analyzed by real-time reverse-transcriptase polymerase chain reaction. We used logistic regression analyses, recessive and codominance models of inheritance, and P < .05 for significance. RESULTS: Six-hundred and thirty-four postmenopausal women were included: 348 (54.8%) POP cases and 286 (45.1%) controls. The frequencies of GG, GA, and AA genotypes for COL1A1 were 69.12%, 20.24%, and 10.59% in POP group and 71.79%, 20%, and 8.21% in controls; GG, GT, and TT for COL3A1 were 37.54%, 59.53%, and 2.93% in POP group and 36.24%, 60.14%, and 3.62% in controls. There were no genotypic or allelic association with POP phenotype that link both SNPs rs1800012 and rs1800255 to increased risk of POP. Vaginal delivery (odds ratio [OR] = 13; 95% confidence interval [CI] [4.00-47.08]), POP family history (OR = 3.1; 95% CI [1.49-6.50]), diabetes mellitus (OR = 2.3; 95% CI [1.08-5.21]), number of pregnancies (OR = 1.2; 95% CI [1.05-1.36]), and age (OR = 1.1; 95% CI [1.09-1.19]), were variables of increased risk for POP (P < .05 for all). CONCLUSION: Our study suggests lack of association between DNA polymorphisms rs1800012 of COL1A1 and rs1800255 of COL3A1 with advanced POP. Vaginal delivery, POP family history, diabetes mellitus, number of pregnancies, and age are risk factors for POP.

The molecular effects of electrical stimulation on the muscle components of the urethra of female rats after trauma by vaginal distention.

AIMS: To evaluate the expression of genes and proteins related to the urethral muscles of female rats after trauma by vaginal distention (VD) and after electrical stimulation therapy (EST). METHODS: We compared the urethras of four groups of 20 animals each: control without trauma (C), 7 (recent-trauma) and 30 days (late-trauma) post-VD, and VD-treated with EST. We evaluated the expression of myogenic regulatory factors MYOD1 and myogenin (MYOG); skeletal muscle myosin heavy chain 1, 2, and 3 (MYH1, MYH2, and MYH3); smooth muscle MYH11; and myosin light chain 9 (MYL9). We used real-time quantitative polymerase chain reaction, Western blot analysis, and immunohistochemistry. RESULTS: MYOD1 and MYOG genes were overexpressed in the recent-trauma group compared with the other groups (P < .05). MYH1 and MYH3 genes were upregulated in the recent-trauma group compared with the control and EST groups (P < .05). The MYH2 gene was overexpressed in the late-trauma group (P < .05), while the MYH2 protein was significantly increased in the EST group compared with control, recent-trauma and late-trauma groups by 5-, 3-, and 2.7-fold change, respectively (P < .05). MYL9 and MYH11 messenger RNA were overexpressed in both trauma groups compared with control and EST groups (P < .05). MYH11 protein was not different among the study groups (P > .05). CONCLUSIONS: EST enhances the recovery of the damaged urethral tissue of rats mainly by acting on the striated-muscle components. The MYH2 pathway underlies the positive effects of EST in the external urethral sphincter.

Molecular and histomorphological evaluation of female rats' urethral tissues after an innovative trauma model of prolonged vaginal distention: immediate, short-term and long-term effects.

INTRODUCTION AND HYPOTHESIS: An animal model of vaginal distention (VD) was developed to reproduce the acute urethral injury and deficiency underlying stress urinary incontinence (SUI). Data on the chronic effects of urethral trauma and the recovery process are still scarce. We investigated acute, short- and long-term histomorphological and molecular changes in the urethra of rats post 12-h intermittent VD. METHODS: We evaluated the urethra of four groups of female rats (n = 72): control without trauma, 1 h, 7 days and 30 days post VD. We compared the gene and protein expression of the VEGF and NGF growth factors, collagens (COL1a1 and COL3a1), desmin, smooth muscle myosin (MYH11), skeletal muscle myosins (MYH1, MYH2 and MYH3) and cell proliferation marker MKi67. We used real-time RT-qPCR, and immunohistochemistry. RESULTS: Histology showed urethral damage after VD mainly involving the muscular layers. VEGF, NGF, desmin and MKi67 mRNA were significantly upregulated in the urethras of rats 1-h post VD compared with controls (P < 0.05 for all). By 7 days post trauma, COL1a1, MYH11 and MYH3 genes were overexpressed compared with controls (p < 0.05 for all). The COL3a1 protein level was increased by 2.6 times by day 7, while MYH2 protein was significantly decreased (around two times) from 7 to 30 days post VD compared with controls (p < 0.05 for both). CONCLUSIONS: The 12-h intermittent VD causes chronic alterations in the urethra represented by increased COL3a1 and decreased MYH2 protein levels in the long term. The model can potentially be used to study the mechanisms of urethral injury and recovery as well as the physiopathology of SUI.

Randomized controlled trial comparing single-incision mini-sling and transobturator midurethral sling for the treatment of stress urinary incontinence: 3-year follow-up results.

BACKGROUND: The role of single-incision mini-slings (SIMS) in stress urinary incontinence (SUI) management is still not elucidated. OBJECTIVE: To compare efficacy and safety of SIMS and transobturator sling (TOT) for SUI after 36-month follow-up. METHODS: A randomized controlled clinical trial involving 130 women with SUI that had either SIMS or TOT. Primary outcomes: objective cure defined as negative cough stress and pad tests, and subjective cure reported as satisfaction and no desire for additional treatment. SECONDARY OUTCOMES: quality-of-life by IQOL and UDI-6 questionnaires, complications and reoperation rates. Student's t, χ2 , Fisher's exact, and Mann-Whitney tests, ANOVA and P < 0.05 as cut-off point were used for statistics. RESULTS: A total of 82 patients (n:41 each arm) completed 36-month follow-up. Objective cure was lower in the SIMS compared to TOT groups by both per protocol (68.3% and 90.2%, respectively, P = 0.027) and intention-to-treat analysis considering missing data as failures (40.6% and 60.7%, respectively, P = 0.035), while similar in both groups (81.2% and 93.4%, respectively) considering missing data as successes. Subjective cure rates were similar for both groups. TOT group presented better outcome regarding the avoidance and limiting behavior domain of IQOL (P = 0.021), and UDI-6 scores (P = 0.026). Seven out of 69 (10.1%) women in the SIMS group compared with two out of 61 (3.3%) in the TOT group (P = 0.172) had repeat surgery due to recurrent SUI at year follow up. CONCLUSION: TOT was associated to higher objective cure rate than SIMS for SUI treatment although satisfaction rate was similar for both groups 3 years postoperative.

Molecular and immunohistochemical analysis of the urethra of female rats after induced trauma and intravenous therapy with muscle derived stem cells.

AIMS: To identify the urethral migration of muscle derived stem cells (MDSCs) after intravenous (IV) injection in rats that underwent vaginal distension (VD) and to analyze the effects of MDSC in the urethra of rats after trauma in regards to: (1) mRNA expression of collagens, Vegf, Ngf, Ki67, Myh11, and Myh2; (2) expression of smooth and striated muscle proteins. METHODS: MDSCs expressing green fluorescent protein (GFP) were injected into the tail vein of rats 3 days after VD. The location of GFP cells was verified at 2 h and at 7 days following IV injection. Urethras of three groups were analyzed: Control, Trauma 7D, and MDSC 7D. Real-time RT-qPCR and immunohistochemistry were performed. RESULTS: MDSCs were identified only after 2 h of the procedure in the urethra. Myh11 gene was overexpressed in the Trauma group in relation to Control. Ki67 gene expression was increased in the MDSC group relative to Trauma and Control. Col1a1 and Col3a1 genes expression were increased in the MDSC group relative to Control. Ngf mRNA level was decreased in the MDSC group in relation to Trauma. Protein expression of Mhy11, Myh2, and Desmin were increased in the MDSC group in relation to Trauma and decreased in the Trauma in relation to Control. CONCLUSION: MDSCs migrated early to the traumatized urethra, but did not integrate into the tissue. MDSC alters the expression of genes related to cell proliferation, neural growth factor and extracellular matrix and the expression of smooth and striated muscle proteins in the traumatized rat urethra.

Collagen XVIII and LOXL-4 polymorphisms in women with and without advanced pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: We verified the presence of single nucleotide polymorphisms (SNP) rs2236479 of the collagen 18 (COL18A1) and rs2862296 of the lysyl oxidase-like 4 (LOXL-4) genes and the association with pelvic organ prolapse (POP) in Brazilian women and determined risk factors for POP development. METHODS: We assessed 532 postmenopausal women divided into POP (stages III and IV) and control (stages 0 and I) groups by examination and peripheral blood sample collection. DNA sequences of interest were analyzed by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). We used logistic regression models for the analyses, with p < 0.005 for significance. RESULTS: The frequency of homozygous polymorphic alleles (AA) in COL18A1 and (GG) in LOXL-4 were similar in both groups (17.5% and 15.4% for COL18A1 and 18.9% and 20.6% for LOXL-4, respectively). There were no associations between those polymorphisms or other genotypes and POP. Multiple logistic regression analysis identified age [odds ratio (OR) = 1.10, confidence interval (CI) 95% = 1.07; 1.14), number of vaginal births (OR = 1.66, CI 95% = 1.36; 2.03), and family history (OR = 2.55 CI 95% = 1.43; 4.55) as independent risk factors for POP. CONCLUSION: Our study suggests lack of association between DNA polymorphisms rs2236479 of COL18A1 and rs2862296 of LOXL-4 with advanced POP in this population.

Hysteropreservation versus hysterectomy in the surgical treatment of uterine prolapse: systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: The efficacy and safety of removing or preserving the uterus during reconstructive pelvic surgery is a matter of debate. METHODS: We performed a systematic review and meta-analysis of studies that compared hysteropreservation and hysterectomy in the management of uterine prolapse. PubMed, Medline, SciELO and LILACS databases were searched from inception until January 2017. We selected only randomized controlled trials and observational cohort prospective comparative studies. Primary outcomes were recurrence and reoperation rates. Secondary outcomes were: operative time, blood loss, visceral injury, voiding dysfunction, duration of catheterization, length of hospital stay, mesh exposure, dyspareunia, malignant neoplasia and quality of life. RESULTS: Eleven studies (six randomized and five non-randomized) were included involving 910 patients (462 in the hysteropreservation group and 448 in the hysterectomy group). Pooled data including all surgical techniques showed no difference between the groups regarding recurrence of uterine prolapse (RR 1.65, 95% CI 0.88-3.10; p = 0.12), but the risk of recurrence following hysterectomy was lower when the vaginal route was used with native tissue repair (RR 10.61; 95% CI 1.26-88.94; p = 0.03). Hysterectomy was associated with a lower reoperation rate for any prolapse compartment than hysteropreservation (RR 2.05; 95% CI 1.13-3.74; p = 0.02). Hysteropreservation was associated with a shorter operative time (mean difference -12.43 min; 95% CI -14.11 to -10.74 ; p < 0.00001) and less blood loss (mean difference -60.42 ml; 95% CI -71.31 to -49.53 ml; p < 0.00001). Other variables were similar between the groups. CONCLUSIONS: Overall, the rate of recurrence of uterine prolapse was not lower but the rate of reoperation for prolapse was lower following hysterectomy, while operative time was shorter and blood loss was less with hysteropreservation. The limitations of this analysis were the inclusion of nonrandomized studies and the variety of surgical techniques. The results should be interpreted with caution due to potential biases.

Genes responsible for vaginal extracellular matrix metabolism are modulated by women's reproductive cycle and menopause.

OBJECTIVES: To analyze the expression of genes involved in extracellular matrix (ECM) biogenesis and remodeling in vaginal tissue of women with clinically normal pelvic floor support (defined as controls) according to the phase of menstrual cycle and postmenopausal women with and without pelvic organ prolapse (POP). MATERIALS AND METHODS: This study examined the expression of matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), and the Lysyl oxidase (LOX) family genes in the anterior vaginal wall of Caucasian women by real-time RT-PCR. Initially, mRNA expression was assessed in premenopausal controls in the secretory (group 1, n = 10) vs. proliferative (group 2, n = 8) phase of menstrual cycle. In addition, we compared premenopausal controls in the proliferative phase (group 2) vs. postmenopausal controls (group 3, n = 5). Finally, we analyzed postmenopausal controls (group 3) vs. postmenopausal women with advanced POP (group 4, n = 13). RESULTS: According to the phase of menstrual cycle, MMP1 was significantly reduced (p = 0.003), whereas the expression of TIMP1 and LOXL4 was significantly up-regulated during proliferative phase (both p < 0.01) when compared to the secretory phase in premenopausal control women. Regarding menopausal status/ageing, all MMPs were down-regulated, while TIMP3, TIMP4 and LOXL2 were significantly up-regulated in postmenopausal control women when compared to premenopausal controls (p = 0.005, p = 0.01 and p < 0.001, correspondingly). TIMP4 and LOXL2 mRNA levels were significantly decreased in postmenopausal POP patients compared to asymptomatic postmenopausal controls (p < 0.01 for both). CONCLUSIONS: Our results indicate that ovarian cycle and age-related changes influence the expression of genes encoding proteins responsible for ECM metabolism in human vagina. Moreover, POP is associated with alteration in vaginal ECM components after menopause.

Correlation between ischemic stroke topography and female urinary incontinence.

AIM: To investigate the association between ischemic stroke topography and the onset of urinary incontinence (UI); to evaluate predictors of post-stroke UI in women. METHOD: We prospectively followed up a cohort of women with ischemic stroke confirmed by clinical and computed tomography (CT) or magnetic resonance imaging (MRI) scans findings. Participants were subjected to interview, clinical evaluation, and urodynamic study if needed at 6 months post-stroke and divided in continent and incontinent groups. Non-parametric tests compared the baseline characteristics among the groups and determined association between post-stroke UI and the brain sites of injury. Logistic regression analysis determined predictors of post-stroke UI. Significance level at 5 % was set. RESULTS: 162 S-women were included: 128 (79 %) continent and 34 (21 %) incontinent. Frontal lobe lesions were higher in the incontinent group (82.9 % versus 51.2 %, p = 0.001); lesions in the parietal lobe and the left cerebral hemisphere were higher in the continent group (40.9 % versus 20 %, p = 0.023; and 61.4 % versus 40 %, p = 0.024, respectively). Frontal lobe injury [RR 3.68 (CI 1.2-11.2)], body mass index (BMI) [RR1.16 (CI 1.062-1.266)] and number of vaginal deliveries [RR 1.358 (CI 1.163-1.585)] are risk factors for post-stroke UI. Left parietal lobe injury is less likely to occur in continent women after 6 months [RR 0.168 (CI 0.029-0.981; p = 0.048)]. CONCLUSION: There is a correlation between the topography of the ischemic stroke and the onset of UI. Frontal lobe lesion, BMI and number of vaginal deliveries are predictors of post-stroke UI.

Expression of genes encoding smooth muscle contractile proteins in vaginal tissue of women with and without pelvic organ prolapse.

AIMS: We hypothesize that the expression of genes encoding vaginal smooth muscle (SM) contractile proteins is altered in patients with pelvic organ prolapse (POP) and is influenced by age and menopausal status. We aim to analyze the expression of SM-myosin heavy chain (MHY11), caldesmon (CALD1), SM gamma-actin (ACTG2), and tropomyosin (TPM1), in premenopausal and postmenopausal women with advanced POP and asymptomatic controls. METHODS: During total hysterectomy we collected anterior vaginal wall biopsy samples from 55 women, 37 premenopausal (23 patients and 14 controls), and 18 postmenopausal women (13 patients and 5 controls). Total mRNA from the tissues was quantified by real-time RT-PCR. RESULTS: MHY11 gene expression was down-regulated in premenopausal POP patients compared to premenopausal controls (fivefold, P = 0.002). In the postmenopausal groups, we observed a sixfold increase in the CALD1 gene expression in POP patients compared to asymptomatic controls (P = 0.03). The gene expression of CALD1, ACTG2, and TPM1 was significantly down-regulated in vaginal tissue of healthy women after menopause (P < 0.05). CONCLUSION: Dysregulation of the vaginal SM content in POP patients involves alteration of different cellular pathways according to age and menopausal status.

Management of Stress Urinary Incontinence With Pelvic Floor Muscle Training for a Woman With Charcot-Marie-Tooth Disease: A Case Report.

Objective: The purpose of this report is to describe the effects of pelvic floor muscle training (PFMT) in stress urinary incontinence (SUI) of a woman with Charcot-Marie-Tooth (CMT) disease. Clinical Features: A 50-year-old female patient with a diagnosis of type II CMT disease was referred to treatment as a result of a complaint of urinary loss upon effort (ie, coughing and sneezing). She reported that the symptoms started about 36 months prior. The urodynamic study revealed SUI with a Valsalva leak point pressure of 84 cmH2O. Intervention and Outcome: The treatment of SUI was carried out through a PFMT program for 12 weeks (with supervision) and exercises at home for another 12 weeks. A specialized physiotherapist measured symptoms and severity of SUI (3-day urinary diary, 1-hour pad test), pelvic floor muscle function (digital palpation, manometry and dynamometry), effect of the SUI on quality of life (Incontinence Quality of Life Questionnaire), and adherence to the outpatient sessions and to home exercise sets, which also were assessed (exercise diary). Conclusion: In this patient with CMT disease, improvements in urinary symptoms and severity of SUI, pelvic floor muscle function, and effect of SUI on quality of life were noted after PFMT.

Expression of Bone Morphogenetic Protein-1 in vaginal tissue of women with severe pelvic organ prolapse.

OBJECTIVES: To analyze the differential gene and protein expression of Bone Morphogenetic Protein-1 in vaginal tissue of women with advanced pelvic organ prolapse and controls. STUDY DESIGN: We sampled the anterior vaginal wall of 39 premenopausal (23 patients and 16 controls), and 18 postmenopausal women (13 patients and 5 controls) during hysterectomy. Total mRNAs and proteins were quantified by real-time RT-PCR and immunoblotting. RESULTS: Bone Morphogenetic Protein-1 gene expression was decreased in pre- and postmenopausal pelvic organ prolapse patients compared with asymptomatic women (P = .01). The expression of 130 kDa, 92.5 kDa, and 82.5 kDa isoforms of Bone Morphogenetic Protein-1 were down-regulated in postmenopausal patients (P = .01), whereas the 130 kDa isoform expression was up-regulated in premenopausal patients (P = .009), when compared with respective controls. CONCLUSION: The Bone Morphogenetic Protein-1 expression in human vagina was altered in patients with severe pelvic organ prolapse and influenced by menopausal status. Dysregulation of Bone Morphogenetic Protein-1 may contribute for a deficient vaginal connective tissue and support.

LOX family enzymes expression in vaginal tissue of premenopausal women with severe pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: The extracellular matrix proteins collagen and elastin provide tissue strength and resilience, whereas lysyl oxidase enzymes play a major role in their stabilization. This study examines the expression and tissue localization of lysyl oxidase family proteins in the anterior vaginal wall of premenopausal women with advanced pelvic organ prolapse (POP, n = 15) and asymptomatic controls (n = 11). All women were in the proliferative phase of menstrual cycle. METHODS: Total mRNAs and proteins extracted from the vaginal tissue were examined by real-time polymerase chain reaction and immunoblotting, and tissue specimens were analyzed by immunohistochemistry. RESULTS: The expression of LOX, LOXL1, and LOXL3 genes as well as LOX and LOXL3 proteins were significantly reduced in POP patients (P < 0.05). Immunolocalization of LOX family proteins was confirmed in all vaginal specimens. CONCLUSION: We proposed that reduced expression of LOX enzymes may result in defective assembly of pelvic tissues and development of POP.