Protective effects of metformin and vitamin C on diabetes-induced testicular dysfunction.

In brief: Diabetes mellitus negatively impacts reproductive health in males. This study demonstrates the protective effects of a combination of metformin and vitamin C on diabetes-induced testicular damage. Abstract: This study aimed to investigate the potential protective effects of combined metformin (Met) and vitamin C (VitC) therapy on diabetes mellitus (DM)-induced testicular damage, sperm parameters, and the regulation of gene and protein expression associated with reproductive function. 36 C57BL mice were divided into six groups: control, VitC, DM, DM+VitC, DM+Met, and DM+VitC+Met. Diabetes mellitus was induced with streptozotocin, and treatment with Met (250 mg/kg/day) and VitC (100 mg/kg/day) for 40 days. Sperm parameters and serum oxidative stress markers were also evaluated. Sperm viability and apoptosis were assessed using Muse Cell Analyzer. Dnah7 and Tomm20 gene expression in the testis was determined by real-time PCR. Spermatogenesis was evaluated using the Johnsen score. Caspase-3 and proliferating cell nuclear antigen levels in the testes were assessed using western blotting and immunohistochemistry. Hyperglycaemia and decreased superoxide dismutase levels were observed in the DM group. Combination therapy resulted in higher sperm viability, Johnsen score, and testicular Tomm20 and Dnah7 mRNA expression levels than monotherapy. The combined administration of Met and VitC has significant potential for managing DM-associated reproductive dysfunction by maintaining sperm viability, Johnsen scores, and testicular protein profiles. Our results suggest that combination therapy holds promise for protecting testicular function and modulating key molecular markers, thereby mitigating DM-induced testicular damage at the molecular level.