Increased Matrix Metalloproteinases-1,-9 in the Uterosacral Ligaments and Vaginal Tissue from Women with Pelvic Organ Prolapse.
Michal Dviri, Elad Leron, Jacob Dreiher, Moshe Mazor, Ruthy Shaco-Levy. Soroka University Medical Center, Beer-Sheva, Israel; Ben-Gurion University, Beer-Sheva, Israel
Background: Pelvic Organ Prolapse (POP) is a widespread disease, associated with significant morbidity, but its pathophysiology is still poorly understood. Reduced collagen content, altered ratios of different collagen types, and increased tissue expression of matrix metalloproteinases (MMPs) have been found in samples of vaginal tissue taken from women with prolapse compared with controls. MMP-1 cleaves type I collagen, the most abundant connective tissue protein. Thus, it may play a critical role in the loss of tissue strength in POP. MMP-9 is a rapid gelatinase degrading MMP-1 cleavage products. Our purpose was to investigate the possible association of increased MMPs-1,-9 expression with POP. Additionally, we aimed to evaluate whether inflammatory processes contribute to POP development, possibly by release of various cytokines.
Design: 40 women who underwent hysterectomy, 20 with POP grade 2 and above, and 20 without POP, participated in the study. Biopsies from the uterosacral ligaments and vaginal mucosa were obtained from each woman. Each biopsy was sectioned and stained with MMP-1 and MMP-9 by immunohistochemical methods and with hematoxyline and eosin (H&E). MMP-1,-9 expression was evaluated on the immunostained slides. Possible inflammatory changes (lymphoplasmacytic infiltrate and vascular proliferation) were examined on the H&E stained slides.
Results: A higher stromal (extra-cellular) expression of MMP-1,-9 was found in POP cases compared with controls in vaginal biopsies (MMP-1: p=0.004, MMP-9: p=0.042) as well as in uterosacral ligaments biopsies (MMP-1: p=0.011, MMP-9: p=0.015). Increased intracellular expression of both MMPs was also demonstrated in fibroblasts in vaginal and uterosacral ligaments biopsies of women with POP (p<0.001 for MMP-1 and MMP-9). The degree of inflammatory changes, reflected by the number of lymphocytes, plasma cells and capillary-sized blood vessels per 10 high power fields, was similar in specimens obtained from women with and without POP.
Conclusions: The expression of MMP-1,9 appears to be increased in tissues from women with POP. It is possible that MMPs-1,-9 contribute to loss of connective tissue strength and thus participate in the pathogenesis of POP. However, it is also plausible that the biomechanical changes associated with POP resulted in the alteration of MMPs expression. Inflammation does not seem to play an important role in the pathogenesis of POP.
Category: Gynecologic & Obstetrics
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 132, Tuesday Afternoon