Synergistic Amelioration of Imidacloprid-Induced fertility impairment by Vitex agnus-castus and Nigella sativa in Female Rats: Mechanistic Evidence of Hormonal and Reproductive Restoration.

BACKGROUND: Imidacloprid, a widely used neonicotinoid pesticide, has been associated with endocrine disruption and reproductive toxicity. Natural phytotherapeutics with hormone-modulating and antioxidant properties may offer protective benefits against such chemically induced reproductive dysfunction. OBJECTIVE: To evaluate the therapeutic potential of Vitex agnus-castus and Nigella sativa, administered individually and in combination, in mitigating imidacloprid-induced fertility impairment in female Wistar rats. METHODS: Female Wistar rats were exposed to imidacloprid (10 mg/kg/day, orally) for 28 days to induce reproductive toxicity. Following exposure, animals received treatment with Vitex agnus-castus extract (250 mg/kg), Nigella sativa extract (150 mg/kg), their combination or clomiphene citrate (1 mg/kg/day for 9 days) as a reference drug. Reproductive hormone levels (LH, FSH and estrogen), fertility outcomes (litter size) and histopathological changes in ovarian and uterine tissues were assessed. RESULTS: Imidacloprid exposure significantly decreased serum LH, FSH, estrogen levels and litter size (p < 0.05), confirming reproductive dysfunction. Treatment with both plant extracts improved hormonal profiles and fertility parameters. The combined therapy demonstrated the most pronounced recovery, producing effects comparable to clomiphene citrate. Histological examination revealed restoration of normal ovarian follicular development and uterine architecture in treated groups. CONCLUSION: Vitex agnus-castus and Nigella sativa, particularly in combination, effectively ameliorated imidacloprid-induced endocrine and reproductive disturbances, suggesting their potential as complementary therapeutic agents against pesticide-related fertility impairment.