Prenatal Chlorpyrifos Exposure Induces Ovarian Toxicity in Rat Offspring: Modulatory Potential of Curcumin

Background: Chlorpyrifos (CPF) is a widely used organophosphate pesticide that can reach the developing organism during gestation. The finite ovarian follicle pool is established early, yet prenatal CPF effects on it remain poorly characterized by unbiased quantitative methods. This study evaluated the developmental ovarian toxicity of prenatal CPF exposure and the modulatory potential of curcumin in rat offspring. Methods: Pregnant Wistar rats were assigned to Control, Sham, CPF (5 mg/kg/day), CUR (100 mg/kg/day), and CPF + CUR groups (five dams per group). Anogenital distance was recorded at birth (PND1). Female offspring were examined at postnatal day 28 using ovarian weight, histopathology, unbiased stereological follicle quantification, cortical volume estimation, serum anti-Müllerian hormone (AMH), serum cholinesterase activity, and biochemical markers of ovarian oxidative status and inflammation. The litter was the unit of analysis (n = 5 litters per group). Results: Prenatal CPF exposure produced marked, quantifiable alterations in ovarian structure, including decreased cortical volume, structural disorganization, vascular alterations, and follicular degeneration. Primordial, preantral, and antral follicle counts were significantly reduced versus controls (p < 0.0001), accompanied by significantly reduced ovarian weight and a shorter anogenital distance at birth. Serum AMH was lower in CPF-exposed offspring, and serum cholinesterase activity was reduced. In the curcumin co-treatment group, changes were partially less pronounced, with better-preserved follicular architecture and higher cortical volume than the CPF group. Ovarian oxidative and inflammatory activity increased with CPF exposure and was less marked with curcumin co-treatment. Reproductive-hormone measurements, including AMH, were not analytically validated in-house and are reported as exploratory. Conclusions: Prenatal CPF exposure induced structural and biochemical alterations consistent with developmental ovarian toxicity in rat offspring. Curcumin co-administration was associated with partially less pronounced changes, suggesting a modulatory rather than a fully protective role. Given the limited number of litters, findings should be interpreted with caution.