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

Background: Imidacloprid, a widely used neonicotinoid pesticide, is associated with endocrine disruption and reproductive toxicity in females. Phytotherapeutics such as Vitex agnus-castus and Nigella sativa have shown promising effects in fertility regulation and hormonal modulation. This study aimed to assess their therapeutic potential, individually and in combination, against Imidacloprid-induced infertility in female Wistar rats. Methods: A total of 48 Wistar albino rats (36 females and 12 males) were divided into seven groups (n = 6). Infertility was induced using Imidacloprid. Test groups were treated with Vitex agnus-castus , Nigella sativa , their combination, or standard clomiphene citrate for 28 days following induction. Hormonal assays (LH, FSH, estrogen, progesterone), fertility index, pup birth rate, and histopathological evaluation of ovaries and uterus were performed. Results: Imidacloprid significantly reduced fertility index, altered reproductive hormones, and caused ovarian and uterine structural damage. Treatment with Vitex agnus-castus and Nigella sativa individually improved hormonal balance, fertility index, and histopathological architecture. Combination therapy demonstrated superior efficacy compared to individual treatments, approaching the effects of clomiphene citrate. Conclusion: Vitex agnus-castus and Nigella sativa confer protection against Imidacloprid-induced infertility through endocrine modulation and restoration of reproductive tissue integrity. Combination therapy exhibited synergistic effects, suggesting potential as a phytotherapeutic strategy for managing pesticide-induced female infertility.