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+/+Leprdb/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 ≤ 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 ≤ 0.05). Treatment of diabetic animals with estradiol restored epithelial thickness (P ≤ 0.05), muscularis area (P ≤ 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.

Estradiol restores diabetes-induced reductions in sex steroid receptor expression and distribution in the vagina of db/db mouse model

“…We further demonstrate that estradiol supplementation in diabetic animals restores most of these diabetes-induced changes in the vagina. Our previous study using the same animal model suggests that the restorative effect of estradiol supplementation occurs despite the persistence of hyperglycemia [19]. Because the vagina is a target tissue for sex steroids, it is likely that diabetes-induced changes in receptor expression impede vaginal tissue physiological function.…”

“…Mice were housed 2-3 animals per cage with food and water available ad libitum. Blood glucose levels were determined at 12 and 16 weeks of age, using an Accu-check blood glucose meter (Roche Diagnostics, Basel, Switzerland) as previously described [15,19]. Animals were considered diabetic when blood glucose level exceeded 250 mg/dl (13.86 mmol/L).…”

“…At the conclusion of the experiments, animals were sacrificed, blood was drawn from the abdominal aorta and allowed to coagulate at 4 • C and centrifuged. Plasma samples were analyzed for estradiol by immunoassay at the Endocrinology Laboratory, Animal Health Diagnostic Center at the Cornell University College of Veterinary Medicine (Ithaca, NY) as previously described [15,19].…”

“…We have reported that type 2 diabetes alters vaginal histoarchitecture and estradiol treatment ameliorates this pathology [19]. To date, however, no studies have investigated the effects of type 2 diabetes on vaginal physiology and the potential disruption of sex steroid receptor signaling in diabetic females.…”

Restoration of Vaginal Epithelial Atrophy in Ovariectomized Rats with Sex Steroid Hormones

“…However a divisive study [29] showed that estrogen treatment in women decreased collagen content compared to placebo treatment. Estradiol administration in diabetic mouse significantly increased the volume of the muscle layer and the lamina propria, but induced less marked changes in elastic fibers [30].…”