Diabetes Mellitus Induces Vaginal Tissue Fibrosis by TGF-beta; 1 Expression in the Rat Model

Abstract

The commonly reported sexual problem in women with diabetes mellitus is lack of vaginal lubrication. It is our hypothesis that reduced vaginal lubrication in diabetic women may result from the structural changes of the vagina. The aim of this study was to investigate in the diabetic rat model the vaginal structures using histochemistry and the expression of TGF-beta 1 using immunohistochemistry. Twenty female Sprague-Dawley rats (200-210 g) were divided into two groups: control and experimental. The experimental group (n = 10) received intravenous injection of streptozotocin (50 mg/kg). After 4 weeks, blood glucose levels were measured, and the vagina of the rat was excised. Serial sections of the vagina were used to perform hematoxylin and eosin (H & E) and Masson's trichrome stains, and for immunohistochemistry to identify TGF-beta 1 expression. The mean blood glucose concentrations were 67 +/- 11 mg/dL (range; 50-85) in the control group and 522 +/- 61 mg/dl (range; 429-590) in the experimental group. In the diabetic animals, vaginal tissue revealed reduced epithelial layers and decreased vaginal submucosal vasculatures compared to the control animals. The collagen connective tissue in the submucosal area of the diabetic animal tissue showed a dense and irregular, distorted arrangement. The immunoreactivity of TGF-beta 1 in the diabetic animals was prominent in the collagen connective tissue, fibroblasts, and smooth muscle fibers, whereas no immunoactivity was detected in the vaginal structures of the control animals. Diabetes mellitus may induce vaginal tissue fibrosis by TGF-beta 1 expression in the rat model. This implies that reduced vaginal lubrication in the diabetic women may result from the structural changes of the vagina.

Sexual dysfunction in diabetic women

“…to electrical stimulation of nerves (EFS), to NO donors, and to calcitonin gene-related peptide (CGRP)] and the contractile response of vaginal tissue to norepinephrine and to EFS. 65 Other rat studies have indicated that diabetes causes a significant decrease in nervestimulated clitoral and vaginal blood flow, induces diffuse fibrosis of the clitoris and the vaginal tissue, and reduces muscular layer and epithelial thickness in the vagina, 63,64,66 thus impairing sexual response. Studies in humans, using vaginal plethysmography as an objective measure of physiological arousal, have found an association between diabetes and decreased vaginal lubrication.…”

“…Studies in animals have indicated that diabetes, by inducing structural and functional changes in the female genital tract, may result in impaired arousal and orgasmic sexual response. 63,64 In a rat model of streptozotocin-induced diabetes it has been shown that diabetes impaired the relaxation responses of the vaginal tissue to almost all transmitter systems [i.e. to electrical stimulation of nerves (EFS), to NO donors, and to calcitonin gene-related peptide (CGRP)] and the contractile response of vaginal tissue to norepinephrine and to EFS.…”

T. gondii Infection Acquired during Pregnancy and/or after Birth may be Responsible for Development of both Type 1 and 2 Diabetes Mellitus

“…HuC/HuD,anti-human neuronal protein HuC/HuD identifies all neuronal cell bodies in the ganglion; NADHd, diaphorase positive [520]. These are important findings because TGF-β system mediated also diabetic renal hypertrophy and fibrosis build-up due to the extracellular matrix production [521,522], and TGF-β1 was found to induce vaginal tissue fibrosis in animal model [523], while the beta cell hypertrophy, beta cell damage and fibrosis, with reduction in insulin secretion, is characteristic for patients with T2DM [7]. In this context, a significant increase of plasma TGF-β1 levels caused by latent T. gondii infection may play a key role in development of pancreatic islet beta cell abnormalities found in T2DM.…”

Protective Effects of Adeno-associated Virus Mediated Brain-derived Neurotrophic Factor Expression on Retinal Ganglion Cells in Diabetic Rats

“…Animals were fasted for 18-24 h and STZ (65 mg/kg) in 0.02 M citrate saline buffer was administered intraperitoneally, as described previously (Giraldi et al 2001;Park et al 2001;Usta et al 2003). The control group animals received citrate buffer only.…”