Effect of estrogen on molecular and functional characteristics of the rodent vaginal muscularis

摘要

Introduction.: Vaginal atrophy is a consequence of menopause; however, little is known concerning the effect of a decrease in systemic estrogen on vaginal smooth muscle structure and function. As the incidence of pelvic floor disorders increases with age, it is important to determine if estrogen regulates the molecular composition and contractility of the vaginal muscularis. Aim.: The goal of this study was to determine the effect of estrogen on molecular and functional characteristics of the vaginal muscularis utilizing a rodent model of surgical menopause. Methods.: Three- to 4-month old Sprague-Dawley rats underwent sham laparotomy (Sham, N=18) or ovariectomy (Ovx, N=39). Two weeks following surgery, animals received a subcutaneous osmotic pump containing vehicle (Sham, Ovx) or 17β-estradiol (Ovx). Animals were euthanized 1 week later, and the proximal vagina was collected for analysis of contractile protein expression and in vitro studies of contractility. Measurements were analyzed using a one-way analysis of variance followed by Tukey's post hoc analysis (α=0.05). Main Outcome Measures.: Protein and mRNA transcript expression levels of contractile proteins, in vitro measurements of vaginal contractility. Results.: Ovariectomy decreased the expression of carboxyl-terminal myosin heavy chain isoform (SM1) and h-caldesmon and reduced the amplitude of contraction of the vaginal muscularis in response to KCl. Estradiol replacement reversed these changes. No differences were detected in the % vaginal muscularis, mRNA transcript expression of amino-terminal MHC isoforms, l-caldesmon expression, and maximal velocity of shortening. Conclusion.: Systemic estrogen replacement restores functional and molecular characteristics of the vaginal muscularis of ovariectomized rats. Our results indicate that menopause is associated with changes in the vaginal muscularis, which may contribute to the increased incidence of pelvic floor disorders with age.