Humanin ameliorates diabetes-induced testicular damage in a streptozotocin-induced mouse model

Diabetes mellitus is a major metabolic disorder closely associated with oxidative stress and male reproductive dysfunction. Humanin, a mitochondria-derived peptide, has been reported to exert cytoprotective, anti-apoptotic and antioxidant effects in various disease models; however, its role in diabetes-induced testicular damage remains unclear. This study aimed to investigate the effects of humanin on oxidative stress parameters in seminal vesicle fluid and histopathological alterations in testicular tissue in a streptozotocin (STZ)-induced diabetic mouse model. A total of 40 adult male Balb/C mice were randomly assigned into four groups: Control, Humanin (HN), STZ, and STZ+HN (n = 10 per group). Diabetes was induced via intraperitoneal administration of STZ (150 mg/kg). Humanin (4 mg/kg) was administered intraperitoneally for 15 days following diabetes induction. Total antioxidant status (TAS), total oxidant status (TOS), and glutathione (GSH) levels in seminal vesicle fluid were measured using ELISA. Testicular tissues were evaluated histopathologically and histomorphometrically. STZ-induced diabetes resulted in a significant decrease in TAS and GSH levels and an increase in TOS levels in seminal vesicle fluid (P < 0.05). Humanin treatment significantly increased TAS and GSH levels while reducing TOS levels compared to the STZ group (P < 0.05). Histopathological analysis demonstrated seminiferous tubule degeneration, germ cell loss, interstitial oedema, and vascular congestion in diabetic mice, whereas these alterations and associated histomorphometric abnormalities were significantly ameliorated following humanin treatment. Humanin attenuated diabetes-induced oxidative imbalance and testicular histopathological damage in STZ-induced diabetic mice. These findings suggest that humanin may exert protective effects against diabetes-associated testicular injury. Further studies are required to elucidate the underlying molecular mechanisms and validate these findings in broader experimental settings.