The effect of prolonged dietary sodium nitrate treatment on the hypothalamus-pituitary-gonadal axis and testicular structure and function in streptozotocin-induced diabetic male rats

Abstract

The aim of this study was to evaluate the effect of prolonged dietary nitrate supplementation on the gonadotropin level, testicular histology and morphometry, expression of miR-34b and p53 mRNA, and spermatogenesis in streptozotocin-induced diabetic male rats. Methods: Fifty male Wistar rats were divided into 5 groups: Control (C), control + nitrate (CN), diabetes (D), diabetes + insulin (DI), and diabetes + nitrate (DN). Diabetes was induced using 45 mg kg⁻¹ of streptozotocin intraperitoneally. Rats in the CN and DN groups were administered sodium nitrate in drinking water (100 mg L⁻¹). NPH insulin (2–4 U d⁻¹) was injected subcutaneously in the DI group for 2 months. Nitrate and insulin supplementation was started one month after confirmation of diabetes. Results: Nitrate supplementation in the DN group significantly increased the body weight (p < 0.05), sperm parameters (p < 0.001), indices of spermatogenesis (p < 0.001), and testis histopathology as well as decreased the blood glucose level (p < 0.001) compared to the untreated diabetic group, although it had no significant effect on testicular parameters, LH and FSH levels. Nitrate administration in the DN group also decreased miR-34b (p < 0.001) and p53 mRNA (p < 0.001) expression, and increased serum insulin and NOx levels compared to the untreated diabetic rats. Conclusions: Chronic nitrate supplementation in streptozotocin-induced diabetic rats improved fertility parameters, which may be associated with increased miR-34b and decreased p53 mRNA.