Resveratrol Mitigates Diabetic Testicular Dysfunction, Endocrine Deficits, and Insulin Resistance via Suppression of Sperm-Endocrine Aberrations and Oxidative Inflammation in Rats

Abstract

Diabetes mellitus (DM) provokes reproductive impairments through endocrine disturbance, sperm deficits, and testicular oxidative inflammation. The study investigated the reproductive protective effects of resveratrol (RSV) against testicular oxidative inflammation, sperm/endocrine deficits, and insulin resistance in streptozotocin- (STZ-, 65 mg/kg) induced DM rat model. Male rats were randomly divided into 4 groups ( $n=6$ ): control, DM, RSV (150 mg/kg bw, orally), and RSV+DM group (21 days). The nontreated DM rats showed marked decreases in serum insulin, reproductive hormones (T, LH, and FSH), and lipid profile levels compared to control. The homeostatic index of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI) were adversely modulated. Sperm count and motility were profoundly decreased, whereas sperm abnormality was significantly increased. The testicular activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and malondialdehyde (MDA) level, along with inflammatory cytokines (TNF-α, IL-6, IL-4, and IL-10) were significantly dysregulated. The DM induced histopathological lesions compared to control rats. Interestingly, the RSV administration to DM rats attenuated the altered reproductive parameters, restored antioxidant mechanism, and anti-inflammatory responses with improved insulin resistance. RSV could prevent DM-induced reproductive deficits and insulin resistance via modulating oxidative stress-mediated testicular inflammation in rats.