Dataset Information

Alteration of vaginal elastin metabolism in women with pelvic organ prolapse.

ABSTRACT: To compare elastin metabolism in the vagina of women with and without pelvic organ prolapse and to define the regulation of this process by hormone therapy (HT).Eighty-seven histologically confirmed full-thickness vaginal biopsies were procured from study participants at time of surgery. Premenopausal women with no prolapse served as controls. Women with prolapse were divided into three groups: premenopausal, postmenopausal not on HT, and postmenopausal on HT. The epithelium was excised leaving the subepithelium, muscularis, and adventitia for analyses. The elastin precursor, tropoelastin, was measured by immunoblotting and mature elastin protein via a desmosine cross-link radioimmunoassay. Matrix metalloproteinases (MMPs)-2 and -9 were quantitated by gelatin zymography. Data were analyzed using Kruskal-Wallis test and post hoc analysis using the Mann-Whitney U test.Tropoelastin (432%), mature elastin (55%), proMMP-9 (90%), and active MMP-9 (106%) were increased in women with prolapse relative to those in the control group while active MMP-2 (41%) was decreased. Comparison of tropoelastin and mature elastin values obtained from the same women showed them to be independently regulated (r=0.19). Interestingly, the highest amount of both proteins occurred in postmenopausal patients not on HT.Elastin metabolism is altered in the vagina of women with prolapse relative to those in the control group, suggesting that vaginal tissue is rapidly remodeling in response to mechanical stretch. We found that elastin levels are highest in the absence of hormones.

SUBMITTER: Zong W

PROVIDER: S-EPMC3042770 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Alteration of vaginal elastin metabolism in women with pelvic organ prolapse.

Zong Wenjun W Stein Suzan E SE Starcher Barry B Meyn Leslie A LA Moalli Pamela A PA

Obstetrics and gynecology 20100501 5

<h4>Objective</h4>To compare elastin metabolism in the vagina of women with and without pelvic organ prolapse and to define the regulation of this process by hormone therapy (HT).<h4>Methods</h4>Eighty-seven histologically confirmed full-thickness vaginal biopsies were procured from study participants at time of surgery. Premenopausal women with no prolapse served as controls. Women with prolapse were divided into three groups: premenopausal, postmenopausal not on HT, and postmenopausal on HT. T ...[more]

PMID: 20410768

Similar Datasets

Project description:The aim of this study was to compare differences in expressions and relationships between key genes involved in extracellular matrix metabolism and tissue cellularity in women with and without pelvic organ prolapse (POP).A total of 80 biopsies (anterior cuff, posterior cuff, and/or leading edge) were obtained from 30 women: n = 10 premenopausal without POP (controls), n = 10 premenopausal with POP, and n = 10 postmenopausal with POP. Quantitative reverse-transcriptase polymerase chain reaction was used to assess gene expression of bone morphogenetic protein 1 (BMP1), collagen types I (COL1) and III (COL3), relaxin family peptide receptor 1 (RXFP1), matrix metallopeptidase 2, and TIMP metallopeptidase inhibitors 2 and 3. Hematoxylin and eosin staining was used to assess cellularity of the connective tissue layer. Kruskal-Wallis test, Mann-Whitney U test, Pearson correlation, or linear regression analyses were used, as appropriate.Bone morphogenetic protein 1 expression was significantly up-regulated in patients with POP compared with controls. Bone morphogenetic protein 1 expression was correlated with COL1 expression in all groups but only correlated with TIMP metallopeptidase inhibitor 3 expression in controls. Similarly, COL3 expression was correlated with RXFP1 expression in women with POP but not in controls. The degree of dependence (slope of the regression line) between COL1 and COL3 expressions was significantly elevated in premenopausal women with POP compared with the other 2 groups. The slopes between COL1-COL3, COL3-matrix metallopeptidase 2, COL1-RXFP1, and COL3-RXFP1 expressions were significantly lower in postmenopausal women compared with premenopausal women with POP. No differences were found in overall tissue cellularity.Bone morphogenetic protein 1 expression may play a significant role in the pathophysiology of POP. The finding that BMP1 expression was correlated with COL1 expression in all groups suggests a conserved association between BMP1 and collagen synthesis in the vaginal wall. The elevated slope between COL1 and COL3 expressions may be associated with early (premenopausal) development of POP. The expression of RXFP1 in postmenopausal women and its altered intergene regulation suggests a role for RXFP1 in connective tissue metabolism outside pregnancy.

Project description:AIM: The molecular etiology of pelvic organ prolapse (POP) is complex and not well understood. We compared the expression/activity of extracellular matrix (ECM)-processing (procollagen I N-proteinase/ a disintegrin and metalloproteinase with thrombospondin motifs [ADAMTS]-2,-3,-14) and ECM-degrading (matrix metalloproteinase [MMP]-1, -2, -7, -8, -9, -12) enzymes and their natural tissue inhibitors (tissue inhibitors of metalloproteinase [TIMP]-1,-2,-3,-4) in vaginal tissues from premenopausal women with advanced POP (POP-Q stage ? 3) and asymptomatic controls (POP-Q = 0). STUDY DESIGN: We sampled the anterior vaginal wall of 36 premenopausal women (17 patients with POP and 19 controls) undergoing total hysterectomy. Exclusion criteria include steroid therapy, malignancy, previous pelvic surgery, and connective tissue diseases. Total RNAs and proteins were quantified by real-time polymerase chain reaction, immunoblotting, and Luminex assay; MMPs activity was analyzed by zymography and tissue localization by immunohistochemistry. RESULTS: The MMP-2 gelatinase activity as well as expression of 58-kDa isoform of ADAMTS-2 was upregulated in patients with POP, irrespective of menstrual phase status, secretory or proliferative, when compared to controls (P < .05). The TIMP-1-4 gene and TIMP-1 protein expression were significantly (P < .05) reduced, whereas protein expression of MMP-12 (pro and active forms) was significantly increased in vaginal biopsies of patients with POP in the proliferative phase of the menstrual cycle compared to corresponding controls. Analyses of MMP-12, TIMP-1, and ADAMTS-2 tissue immunostaining indicate similar localization in the vaginal specimens from control and patients with POP. CONCLUSION: Expression of ECM-remodeling proteins is altered in the vagina of premenopausal patients with severe POP. We speculate that dysregulation of MMP/TIMP complexes and ADAMTS-2 proteins may cause connective tissue defects, which result in weakened vaginal wall support and POP development.

Dataset Information

Alteration of vaginal elastin metabolism in women with pelvic organ prolapse.

Publications

Alteration of vaginal elastin metabolism in women with pelvic organ prolapse.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets