| IntroductionStress urinary incontinence (SUI) is a serious common chronic disease of the middle-aged and old women. Stress urinary incontinence (SUI) is a leakage of urine during moments of physical activity that increases abdominal pressure. Its cause is complex, age is one of the main risk factors of the disease, and however, its pathogenesis is still unclear. According to the well-recognized SUI pathogenesis theories, that is, the integral theory and hammock hypothesis, the imperfection of the structure and function of the urethral support tissues leads to the occurrence of SUI. The urethral support tissue is composed of a large number of extracellular matrix (ECM) and a small amount of cells with fibroblast as the main component. Studies have shown that the obstacle of ECM remodeling is a key factor in the onset of SUI, and estrogen directly involved in the reconstruction process of ECM. Aquaporins (APQs) may transport water selectively and efficiently, and participate in cell migration, associated with a variety of tissue damage repair. Studies showed that an estrogen-response element was identified in the Aquaporin2(AQP2) promoter, confirmed that estrogen dose-dependently increased AQP2expression in endometrial cell, thereby promoting endometrial cell migration, invasion, adhesion and proliferation. In this study, AQP2was localized in fibroblasts of female urethral support tissues by immunofluorescence, and western blot method was employed to observe the expression differences of AQP2in fibroblasts of female urethral support tissues among premenopausal SUI, premenopausal control, postmenopausal SUI and postmenopausal control to explore the correlation of AQP2expression and SUI. By measuring serum estradiol (E2) levels to explore the relevance of AQP2expression in fibroblasts of female urethral support tissues and serum E2levels.Materials and Methods:Anterior vaginal wall tissues (urethral support tissues) were obtained from36women who visited the Women’s Hospital, School of Medicine, Zhejiang University from January2013to March2014, including9cases of premenopausal SUI,9cases of premenopausal control,9cases of postmenopausal SUI and9cases postmenopausal control. The anterior vaginal wall was collected during operations due to urinary incontinence (SUI group) or Paraurethral cyst, Urethral diverticulum and vaginal wall cyst near the urethra (control group). Vaginal wall with the size of0.5*1cm2that is near the urethra were derived as study specimens. The fibroblasts were obtained by primary culture of fresh specimens of female urethral support tissues, and identified by immunohistochemistry. The immunofluorescence technique was carried out to determine the expression of the all subtypes of AQPs in the fibroblasts. The Western blot assay was conducted to investigate the expression of AQP2protein in the fibroblasts. Serum E2levels were determinated by ECLIA method.Results1. The immunofluorescence techniques and Western blot assay showed that AQP2expressed in the fibroblasts of urethral support tissue.2. T test demonstrated that the age, delivery times, BMI and menopause were similar among the all study specimens. Serum E2levels in the premenopausal SUI group, premenopausal control group, postmenopausal SUI group and postmenopausal control group were311.43±93.63nmol/L,530.30±232.21nmol/L,39.91±16.76nmol/L and31.30±9.95nmol/L. There were differences between the premenopausal SUI group and premenopausal control group (P<0.05), and similar between the postmenopausal SUI group and postmenopausal control group (P>0.05).In addition, there were significant negative correlation between serum E2levels and AQP2in fibroblasts of all urethral support tissues (r=-0.537, P<0.05) and in fibroblasts of urethral support tissues with SUI(r=-0.860, P<0.05).3. T test demonstrated that the expression of AQP2in fibroblasts of urethral support tissue were similar between general SUI group (26.29±2.53) and general control group(25.32±3.80)(P>0.05), the expression of AQP2in fibroblasts of total postmenopausal urethral support tissue(28.36±1.31) increased significantly than in fibroblasts of total premenopausal urethral support tissue(23.25±2.40)(P<0.05).The protein expression of AQP2in fibroblasts of urethral support tissue in the premenopausal SUI group, postmenopausal SUI group, premenopausal control group and postmenopausal control group were24.03±0.98,28.54±1.11,22.46±3.15and28.19±1.54.The level were similar between premenopausal SUI group vs. premenopausal control group(P>0.05) and postmenopausal SUI group vs. postmenopausal control group(P>0.05). The level in postmenopausal SUI group increased significantly than in premenopausal SUI group (P<0.05). The level in postmenopausal control group increased significantly than in premenopausal control group (P<0.05) too.Conclusion1. AQP2expressed in fibroblasts of female urethral support tissues.2. The expression of AQP2is closely associated with Serum estrogen levels. We hypothesized that low estrogen levels might increase AQP2expression in fibroblasts of postmenopausal urethral support tissue, resulted in the expression of AQP2increased significantly in fibroblasts of urethral support tissues of postmenopausal women with SUI compared to the premenopausal women with SUI. |
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