Developmental reproductive impacts of gestational polystyrene nanoplastics exposure: precocious puberty and impaired ovarian reserve in female offspring.

Dietary ingestion of nanoplastics through contaminated food and drinking water has become a pressing human health concern. Despite this pressing health concern, the developmental reproductive impacts of gestational nanoplastics exposure on female offspring remains poorly characterized. Using ICR mouse models subjected to prenatal exposure to 60-nm polystyrene nanoplastics (PS-NPs: 5, 50, or 500 mg/kg/day), this study demonstrated that maternal perinatal PS-NPs exposure significantly disrupted ovarian development, induced precocious puberty, and caused ovarian follicular depletion in female offspring, evidenced by reduced ovarian coefficients, advanced vaginal opening, depleted primordial follicles, and elevated atretic follicles. Mechanistically, ovarian development dysregulations arise from suppressed FOXL2-CYP19A1 signaling and downregulated RSPO1/WNT4/β-catenin pathways, while precocious puberty is driven by earlier elevation of serum GnRH levels and hypothalamic reprogramming. Quantitative proteomics reveals dose-dependent pathway alterations: low-dose PS-NPs dysregulate immune/estrogen responses, whereas high-dose exposure causes steroidogenic disruption and apoptotic dysregulation. Serum hormone profiling showed markedly reduced AMH/E2 and elevated LH, corroborated by transcriptional downregulation of key receptors (amh, ERα, and AR). These findings highlight a potential risk to fetal ovarian development posed by maternal nanoplastics exposure, urging the incorporation of developmental and reproductive toxicity into the comprehensive risk assessment of human exposure to micro/nano-plastics.