Estradiol Ameliorates Diabetes-Induced Changes in Vaginal Structure of db/db Mouse Model

Abstract

INTRODUCTION: Women with diabetes experience diminished genital arousal, reduced vaginal lubrication, vaginal atrophy, dyspareunia, and increased infections. Limited studies are available investigating the effects of diabetic complications on the vagina. AIMS: The goals of this study were to investigate type 2 diabetes-induced changes in vaginal structure, and to determine if estradiol treatment ameliorates these changes. METHODS: Eight-week-old female diabetic (db/db) mice (strain BKS*Cg-m+/+Lepr(db)/J) and age-matched control normoglycemic female littermates were used to investigate the effects of type 2 diabetes on vaginal tissue structural integrity. Diabetic animals were divided into two subgroups: diabetic treated with vehicle only and diabetic treated with pellets containing estradiol. At 16 weeks, the animals were sacrificed, and the vaginal tissues were excised and analyzed by histological and immunohistochemical methods to assess diabetes-induced changes in vaginal tissue and the extent by which these parameters are restored by estradiol treatment. MAIN OUTCOME MEASURES: The effects of type 2 diabetes and estradiol supplementation were investigated on vaginal histoarchitecture. RESULTS: Diabetic animals exhibited high blood glucose levels (>600 mg/dL), increased body weight (43.0 +/- 6.0 g vs. 24.4 +/- 2.0 g), and reduced plasma estradiol levels (65.5 +/- 6.6 pg/mL vs. 80.77 +/- 13.2 pg/mL) when compared to control animals. Diabetes resulted in significant thinning of the epithelium (P <or= 0.05), marked decrease in the muscularis area (P </= 0.05), distinct truncation of elastic fibers, and significant reduction of the nitrergic immunoreactive nerve fibers (P <or= 0.05). Treatment of diabetic animals with estradiol restored epithelial thickness (P <or= 0.05), muscularis area (P <or= 0.05), and elastic fiber distribution, and partially restored the density of nitrergic nerve fibers. CONCLUSIONS: The data in this study demonstrate that type 2 diabetes disrupts vaginal structural integrity and that estradiol supplementation ameliorates the diabetes-induced vaginal pathology.