Ascorbic acid alleviates reproductive toxicity of di-(2-ethyl hexyl) phthalate in female Wistar rats

Objective: To investigate the potential of ascorbic acid in mitigating reproductive toxicity induced by di-(2-ethyl hexyl) phthalate (DEHP) in female Wistar rats, focusing on oxidative stress, hormone levels, and gonadotropin receptors expression. Methods: Forty female Wistar rats [30 days old, weighing (60±10)g] were randomly divided into five groups ( n =8 per group). Group 1 received corn oil (control). Groups 2 and 3 were administered DEHP at 10 and 100 mg/kg body weight (b.wt.), respectively. Groups 4 and 5 received DEHP at 10 and 100 mg/ kg b.wt., respectively, plus ascorbic acid 100 mg/kg b.wt.. All treatments were given orally for 30 days. Blood and ovarian tissues were collected to assess serum reproductive hormones, gonadotropin receptor gene expression, oxidative stress markers, and apoptosis. Results: DEHP, particularly at the higher dose, significantly decreased hormone levels (follicle-stimulating hormone, luteinizing hormone, estradiol) and gonadotropin receptor gene expression ( FSHR, LHR ), while increasing oxidative stress and apoptosis. Co-treatment with ascorbic acid significantly improved these parameters, reducing oxidative stress and apoptosis, and restoring hormone levels and gonadotropin receptor expression. Histopathology revealed fewer atretic follicles and less disruption in ovarian structure in DEHP and ascorbic acid-treated groups compared to those treated with DEHP alone. Conclusions: Ascorbic acid demonstrates protective effects against DEHP-induced reproductive toxicity in female rats, likely through mitigating oxidative stress and normalizing hormone levels and ovarian function.