Impact of diabetic hyperglycaemia and insulin therapy on autophagy and impairment in rat epididymis

Blood glucose dysregulation and hyperglycaemia caused by diabetes mellitus are intimately associated with male infertility. Two-month-old Sprague-Dawley rats were given a single dose of streptozotocin (55 mg/kg) by intraperitoneal injection to induce type I diabetes mellitus (DM group). The treatment group was given 1 unit/day of insulin for 16 weeks (INS group). The normal control group (NC group) was given food ad libitum. In the DM group, the histological analysis of caput and cauda epididymal ducts showed broken stereocilia and more lipid vacuolisations in the principal cells. The interstitial hyperplasia and inflammatory cell infiltration were observed in epididymal tissues. Transmission electron microscopy observation showed that the principal cells in the DM group contained more vacuoles, partly lost stereocilia, and swollen mitochondria. The autophagosomes were observed as well. Western blotting results of LC3II/I and P62 protein expression indicated that autophagy was downregulated in the DM group. The total antioxidant activity and GPx5 expression of epididymal tissues were also decreased. In the INS group, significant improvements were observed in epididymal tissues. Our study suggests that diabetic hyperglycaemia causes autophagy dysregulation in epididymal tissues, which may play a role in diabetes-induced rat epididymal injury. Insulin treatment is beneficial for diabetic-associated epididymal dysfunction.