Prenatal exposure to polystyrene nanoplastics impairs offspring fertility in mice by disrupting meiotic recombination and chromatin accessibility in oocytes.

Polystyrene nanoplastics (PS-NPs) are ubiquitous environmental contaminants capable of crossing the placental barrier, yet their impact on mammalian germline development and the reproductive potential of the subsequent generation remains poorly understood. To elucidate the intergenerational effects of prenatal PS-NPs exposure on female offspring fertility and dissect the underlying molecular mechanisms governing oocyte meiotic defects, we established a mouse model of prenatal PS-NPs exposure by administering daily oral gavage of PS-NPs (10 mg/kg/day) and employed an integrative multi-omics strategy combining single-cell transcriptomics (scRNA-seq), chromatin accessibility profiling (scATAC-seq), and functional cellular assays. We demonstrate that prenatal exposure to PS-NPs induced a marked decline in the fertility of female offspring. At the cellular level, PS-NPs delayed meiotic prophase I progression and severely compromised homologous recombination. Mechanistically, PS-NPs disrupted the global chromatin accessibility and epigenetic homeostasis of oocytes. Specifically, we observed aberrant histone modifications, characterized by reduced acetylation and increased ubiquitination/SUMOylation, along with restricted chromatin accessibility at loci critical for meiotic axis assembly and recombination. Furthermore, we identified a distinct subpopulation of arrested zygotene oocytes undergoing apoptosis and autophagy driven by this chromatin dysregulation. Collectively, our findings uncover a novel epigenetic mechanism by which environmental nanoplastics impair meiotic integrity, highlighting chromatin remodeling as a vulnerable target of nanotoxicity, and provide critical insights into the long-term reproductive risks posed by plastic pollution.