Polystyrene nanoplastics impair placental function and promote embryo resorption through ROS-mediated ferroptosis-related injury.

Polystyrene nanoplastics (PS-NPs) are widespread environmental pollutants that have attracted growing concerns regarding reproductive health. Nevertheless, their effects on spontaneous abortion (SAB) and the underlying mechanisms remain unclear. In this study, we investigated the reproductive toxicity of 50 nm PS-NPs using a pregnant mouse exposure model and HTR-8/SVneo trophoblast cells. In vivo, PS-NPs crossed the placental barrier, disrupted placental structure, altered pregnancy-related hormone levels, and increased embryo resorption. In vitro, PS-NPs reduced trophoblast cell viability and migration, induced cell cycle arrest and apoptosis, and caused mitochondrial dysfunction. Combined transcriptomic and metabolomic analyses further demonstrated that PS-NPs disrupted glutathione and glycerophospholipid metabolism and enriched pathways associated with ferroptosis. Mechanistically, PS-NPs induced reactive oxygen species (ROS) accumulation, glutathione depletion, iron overload, lipid peroxidation, GPX4 downregulation, and ACSL4 upregulation, indicating activation of ferroptosis. Functional rescue experiments in HTR-8/SVneo cells revealed that the ferroptosis inhibitor Ferrostatin-1 partially alleviated PS-NPs-induced ferroptotic injury, whereas the ROS scavenger N-acetylcysteine partially reduced ROS accumulation and improved mitochondrial function. Collectively, our findings suggest that PS-NPs exposure impairs placental function and pregnancy maintenance, with ROS-mediated ferroptosis-related trophoblast injury potentially involved, providing novel insights into the reproductive toxicity of nanoplastics during pregnancy.