Mohammad Bostanifard, Hamid Reza Moradi, Zabihollah Khaksar, Sajjad Abbasi, Behzad Shirkavand Hadavand, Milad Faraji
• PS-NPs cross placenta and accumulate in fetal and postnatal ovaries. • Maternal PS-NP exposure disrupts folliculogenesis and ovarian structure. • Oxidative stress and hormonal imbalance accompany PS-NP–induced toxicity. • Ovarian damage from PS-NPs persists from gestation through postnatal stages. Polystyrene nanoplastics (PS-NPs) are emerging environmental contaminants that can cross biological barriers and accumulate in the reproductive organs. This study evaluated developmental ovarian toxicity after maternal and lactational PS-NP exposure in rats on gestational day 20 (GD20) and postnatal days 30 and 60 (PD30, PD60). Pregnant Sprague–Dawley rats were administered PS-NPs at doses of 0.1, 1, or 10 mg/kg/day during gestation and lactation. At GD20, fetal ovaries from exposed dams showed a significant reduction in primordial follicle number and diameter, early granulosa cell disorganization, and a lower parenchyma-to-stroma ratio, indicating impaired folliculogenesis. By PD30 and PD60, ovarian alterations intensified in a dose-dependent manner, including granulosa layer thinning, follicular degeneration, and cortical disarray, which were most pronounced in the high-dose group. Fluorescence microscopy confirmed the transplacental and lactational transfer of rhodamine-labeled PS-NPs, with persistent and dose-dependent accumulation in the follicles and stroma. Biochemically, PS-NP exposure increased the total oxidant status (TOS) and oxidative stress index (OSI) while decreasing the total antioxidant capacity (TAC). Serum estradiol and progesterone levels declined markedly, consistent with oxidative and endocrine disruption. Immunohistochemistry revealed the upregulation of P53 and downregulation of BCL-2, indicating apoptosis-mediated ovarian injury. These findings demonstrate that combined gestational and lactational PS-NP exposure causes persistent, dose-dependent ovarian damage from the fetal stage through postnatal development, highlighting the reproductive risks associated with maternal nanoplastic exposure in an increasingly polluted environment.