Empagliflozin improves sperm quality in diabetic rats by lowering oxidative stress and reducing apoptosis-related genes expression

Abstract

Type 2 diabetes mellitus (T2DM) negatively impacts sperm health by increasing oxidative stress. Empagliflozin, a type of sodium-glucose cotransporter 2 (SGLT2) inhibitor, not only reduces blood glucose levels in T2DM but also has antioxidant properties. This study aimed to investigate the antioxidant effects of empagliflozin on sperm quality and spermatogenesis indices in rats with T2DM.Male rats were divided into three groups (n = 6): control, diabetes mellitus (DM, induced by streptozotocin + nicotinamide), and DM treated with empagliflozin (10 mg/kg, 56 days, via gavage). Sperm parameters including sperm count, viability, motility, normal morphology, DNA integrity, maturation, tail length, and daily sperm production were analyzed. Additionally, spermatogenesis indices, Bax/Bcl2 ratio and serum levels of superoxide dismutase (SOD), total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured. In the DM group, there was a significant decrease in the mean sperm parameters, SOD, TAC, and spermatogenesis indices, along with a significant increase in the percentage of single-stranded DNA (AO⁺), immature sperm nuclei (AB⁺), MDA levels, and Bax/Bcl2 ratio, compared to the control group. In the DM + empagliflozin group, there was a significant increase in the mean sperm parameters, SOD levels (P˂0.001), and spermatogenesis indices. Additionally, there was a significant decrease in the mean AB+ (P˂0.01), AO⁺, MDA levels (P˂0.001), and Bax/Bcl2 ratio compared to the DM group. The results showed that empagliflozin can mitigate the adverse effects of diabetes and improve sperm quality and increase sperm production in diabetic rats.