Impact of diabetes mellitus on female reproductive physiology: Role of oxidative stress and metabolic dysregulation

Diabetes mellitus is a chronic metabolic disorder marked by persistent hyperglycaemia and associated with significant reproductive dysfunctions, particularly affecting ovarian morphology and function. Hyperglycaemia-induced oxidative stress and hormonal imbalances impair folliculogenesis and steroidogenesis, leading to fertility issues and adverse pregnancy outcomes . Among antidiabetic therapies, insulin and metformin are widely used for glycaemic control, while canagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, is gaining attention for its systemic antioxidant and anti-inflammatory effects. This study aimed to evaluate and compare the histological effects of insulin, metformin, and canagliflozin on the ovaries of streptozotocin (STZ)-induced type 2 diabetic pregnant Wistar rats. Thirty-five adult female Wistar rats were randomly assigned into five groups: Group A (non-diabetic control), Group B (diabetic untreated), Group C (diabetic + insulin), Group D (diabetic + metformin), and Group E (diabetic + canagliflozin). Diabetes was induced using intraperitoneal STZ injections (45 mg/kg and 35 mg/kg), and treatments were administered accordingly. After 28 days, the animals were sacrificed, and ovarian tissues were harvested for histological examination. Results indicated significant reductions in blood glucose levels in insulin, metformin, and canagliflozin-treated groups compared to the diabetic untreated group (p<0.05), with canagliflozin showing the greatest glycaemic improvement. Histologically, ovaries in the diabetic untreated group exhibited mild stromal alterations. Insulin-treated ovaries revealed stromal fatty degeneration, while metformin-treated ovaries maintained near-normal histoarchitecture. Canagliflozin-treated ovaries displayed the most preserved ovarian structure, comparable to control, with well-formed follicles and normal stroma. In conclusion, while all antidiabetic agents offered varying degrees of ovarian protection, canagliflozin showed superior efficacy in restoring ovarian morphology and improving metabolic status, suggesting its potential advantage in preserving fertility during diabetic pregnancy.