Potential of Stevia rebaudiana Bertoni Aquatic Extract in Treating Diabetes-Induced Infertility: Effects on Autophagy and Apoptosis.

Background: Infertility is one of the major complications of diabetes. Diabetic-mediated oxidative stress could destroy autophagy in testes, leading to damaged sperm and male infertility. Stevia rebaudiana Bertoni is a medicinal herb with various health-beneficial effects, such as improving diabetes-induced infertility. However, till now, no exact mechanism is known for its effects on diabetic testes. This study aimed to investigate the anti-infertility role of S. rebaudiana aqueous extract in diabetic rats induced by streptozotocin (STZ) by focusing on autophagy and apoptosis pathways and antioxidant activity. Methods: Male rats were divided into four groups of five, including a healthy control group, a diabetic control (STZ) group, and metformin (MET)-treated (500 mg/kg) and stevia-treated (400 mg/kg) diabetic groups for 30 days. After the experimental period was over, rats were sacrificed. Testes tissue and blood samples were prepared for biochemical, molecular, and histopathological analyses. Results: Treatments with stevia and MET significantly increased body weight and testosterone levels and decreased FBS compared to the STZ group. Moreover, both treatments decreased the mRNA expression of Akt1, Mtor, Sqstm1/p62, Nfkb1 and caspase-9 and increased the expression of Becn1, Atg3, Atg5, Atg7, Map1lc3b/LC3B, Nrf2 and Bcl2, suggesting a possible improvement in autophagy- and apoptosis-related responses in diabetic rats. Histopathological changes and sperm characteristics also showed improvement following stevia and MET treatments. Conclusions: Stevia aqueous extract could exert potential therapeutic effects on diabetes-induced infertility in diabetic rats, possibly through the modulation of autophagy, apoptosis, and antioxidant activity.