Microarray analysis of differentially expressed genes in vaginal tissues from women with stress urinary incontinence compared with asymptomatic women

Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305-5317, USA.
Human Reproduction (Impact Factor: 4.57). 02/2006; 21(1):22-9. DOI: 10.1093/humrep/dei276
Source: PubMed


The pathophysiology of pelvic floor dysfunction resulting in stress urinary incontinence (SUI) in women is complex. Evidence suggests that there is also a genetic predisposition towards SUI. We sought to identify differentially expressed genes involved in extracellular matrix (ECM) metabolism in vaginal tissues from women with SUI in the secretory phase of menses compared with asymptomatic women.
Tissue samples were taken from the periurethral vaginal wall of five pairs of premenopausal, age-matched SUI and continent women and subjected to microarray analysis using the GeneChip Human Genome U133 oligonucleotide chip set.
Extensive statistical analyses generated a list of 79 differentially expressed genes. Elafin, keratin 16, collagen type XVII and plakophilin 1 were consistently identified as up-regulated ECM genes. Elafin, a serine protease inhibitor involved in the elastin degradation pathway and wound healing, was expressed in pelvic fibroblasts and confirmed by Western blot, quantitative competitive PCR and immunofluorescence cell staining.
Genes involved in elastin metabolism were differentially expressed in vaginal tissue from women with SUI, suggesting that elastin remodelling may be important in the molecular aetiology of SUI.

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Available from: Yan Wen, May 13, 2014
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    • "Numerous genes, including actin, myosin, ECM-associated genes and transcription factors, have been studied and shown to be associated with POP (11–13). However, there have been a limited number of studies investigating the role of immune-associated genes in POP. "
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    ABSTRACT: Interferon (IFN)-γ is a potent proinflammatory molecule. However, few studies have investigated the expression levels of IFN-γ during pelvic organ prolapse (POP). In the present study, the expression levels and tissue localization of IFN-γ and its pathway-associated genes were detected in the vaginal walls of premenopausal females with POP and asymptomatic controls using quantitative polymerase chain reaction and immunohistochemistry. When compared with the matched controls, an 8.6-fold increase in IFN-γ, 3.8-fold increase in IFN-γ receptor (IFNGR)1, 2.6-fold increase in IFNGR2, 3.4-fold increase in signal transducer and activator of transcription-1, 2.2-fold increase in janus kinase-1 and 5.1-fold increase in nuclear factor (NF)-κB mRNA expression levels were observed in the females with premenopausal POP. In all the females with POP, higher mRNA expression levels of IFN-γ and its receptors were observed when compared with the controls. Expression levels of all the proteins were detected by immunohistochemistry, and the results demonstrated higher staining for IFN-γ, IFNGRs and pathway-associated genes in females with POP. Therefore, the results indicated that IFN-γ may be used as an inflammatory marker for POP development, and is associated with NF-κB.
    Full-text · Article · Oct 2014 · Experimental and therapeutic medicine
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    • "Recent studies have identified genes that encode for components of the extra cellular matrix and these are thought to predispose some individuals to UI [3,16]. Analysis of endopelvic fascia biopsies in women with UI, shows that their tissues have increased degradation of nascent collagen and collagenolytic activity [16]. These findings indicate a strong link between genetics and risk for UI. "
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    ABSTRACT: Background Urinary incontinence (UI) continues to affect millions of women worldwide and those living in resource poor settings seem to be more affected. The purpose of this study was to determine the prevalence of UI and factors associated with UI symptom severity (UISS) among women in a selected district in India. Methods A cross-sectional design was used to collect data from a sample of 598 community dwelling women in the age range of 20 to 60 years. Data was collected using a questionnaire survey of participants who were found in their homes. Results The prevalence of UI was 33.8% and the majority of women had negative attitudes about the condition. For instance most women were in agreement with statements such as: UI cannot be prevented or cured (98%); women with UI are cursed (97%); women are not supposed to tell anyone about the problem (90%) and others. Of the 202 women with self-reported UI, the majority reported having moderate UISS (78%) and others rated the symptoms as mild (22%). The woman’s age at first birth (p<.01) was negatively associated with UISS, while the number of pregnancies (p<.01) and weight of the largest baby ever delivered (p<.01), were positively associated with UISS. The weight of the largest baby delivered had the strongest impact on predicting UISS. Conclusions Many community dwelling women are suffering from UI at proportions which warrant significant public health consideration. Therefore public health programs to prevent UI or worsening of symptoms are required and should emphasize health education, because of the pervasive negative attitudes among affected and unaffected women. The predictors reported here can be used to priotize care for affected women and to encourage early uptake of health actions and behaviors that promote pelvic floor strengthening in at risk women who may be reluctant to disclose UI.
    Full-text · Article · Apr 2013 · BMC Women's Health
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    • "Birth trauma from vaginal delivery may include denervation damage, ischemia and mechanical injuries to the muscular, nervous and connective components of the lower urinary tract tissues [3,9–12]. Recent studies have indicated that in SUI-affected periurethral connective tissues, the metabolism of collagen and elastin is altered [13] [14] [15]. Lysyl oxidase (LOX), an extracellular matrix (ECM) remodeling enzyme, is required for the oxidative deamination of lysine residues in collagen and elastin molecules required for fiber cross-linking. "
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    ABSTRACT: The molecular mechanisms underlying stress urinary incontinence (SUI) are not clear. This study was conducted to evaluate molecular alterations in the urethras of mice with experimentally induced SUI. Eighteen virgin female mice were equally distributed into three groups as follows: two groups undergoing vaginal distension (VD) for 1 h with 3 mm and 8 mm dilators each, and a non-instrumented control group. Changes in leak point pressure (LPP), morphology, lysyl oxidase (LOX) expression and the metabolism of urethral connective tissue were assessed. The LPP was significantly decreased in the 3 mm and 8 mm VD groups compared with that in the control group. Collagen and elastin expression in the urethra was significantly decreased in the 8 mm VD group compared with that in the control group, while LOX expression was significantly enhanced. SUI following vaginal trauma involves over-expression of LOX and decreased synthesis of extracellular matrix components or increased proteolysis in the urethra.
    Full-text · Article · May 2012 · European journal of obstetrics, gynecology, and reproductive biology
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