Hum. Reprod. Advance Access originally published online on February 1, 2006
Human Reproduction 2006 21(5):1266-1273; doi:10.1093/humrep/dei485
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Do extracellular matrix protein expressions change with cyclic reproductive hormones in pelvic connective tissue from women with stress urinary incontinence?
Stanford University School of Medicine, Stanford, CA, USA
1 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, Stanford University School of Medicine, 300 Pasteur Drive, HH-333 Stanford, CA 94305-5317, USA. E-mail: yanwen{at}stanford.edu
BACKGROUND: To evaluate differential expression of transforming growth factor (TGF-
1), latent transforming factor-binding proteins (LTBP-1, LTBP-2) and elastin microfibril components (fibrillin-1 and fibrillin-2) in vaginal tissue from women with stress urinary incontinence (SUI). METHODS: In this case–control study, vaginal tissue from women in both phases of the menstrual cycle was obtained. Messenger RNA (mRNA) expressions of LTBP-1, LTBP-2, fibrillin-1, fibrillin-2 and TGF-1 were determined by relative real-time quantification PCR. Tissue localization was analysed by immunohistochemistry, and semiquantitative protein expression was evaluated by Western blot analysis. RESULTS: Vaginal wall fibroblasts synthesized all proteins tested. LTBP-1, LTBP-2 and TGF-1 co-localized with elastin microfibrils, fibrillin-1 and fibrillin-2 in the extracellular matrix. LTBP-1 mRNA and protein expressions were higher in control versus women affected with SUI in the proliferative phase (P = 0.04), while in the secretory phase, mRNA expression in cases was higher (P = 0.04). Fibrillin-1 mRNA was higher in women affected by SUI versus controls in both phases, but no statistical differences in fibrillin-1 protein expression were observed between the two groups in either phase. LTBP-2 and TGF-1 mRNA expressions showed the same trends as LTBP-1. CONCLUSION: LTBP-1, LTBP-2, TGF-1, fibrillin-1, and fibrillin-2 expressions are hormonally regulated in vaginal wall fibroblasts and differ in women affected by SUI when compared to controls. These data suggest a mechanism to regulate TGF-1 activity in pelvic connective tissue.
Key words:
elastin/fibrillin/latent transforming factor-binding proteins/stress urinary incontinence/transforming growth factor-
This study is supported by National Institutes of Health Grant R401 AGO1790 (to M.L.P.)
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