Polystyrene micro- and nanoplastics exposure during pregnancy compromises offspring skin barrier function via interference with PPAR-mediated lipid metabolism

The ubiquitous presence of micro- and nanoplastics (PS-MNPs) in the environment has raised significant concerns regarding their potential developmental toxicity. However, the impact of maternal polystyrene(PS) - MNP exposure on the skin barrier function of offspring remains unknown. In this study, pregnant mice were exposed to PS-MPs and PS-NPs (10 mg/L) via drinking water during gestation. We assessed the neonatal (P0) skin development through histological analysis and trans-epidermal water loss (TEWL) measurements. Multi-omics approaches were employed to identify toxic mechanisms. HaCaT cells were employed as an in vitro model to investigate cellular uptake, localization, and cytotoxicity of PS-MNPs. Maternal exposure to both PS-MPs and PS-NPs significantly impaired epidermal barrier development in P0 offspring. At an exposure level of 10 mg/L, TEWL values were significantly elevated, accompanied by a compensatory increase in epidermal thickness. Multi-omics analysis revealed that PS-MNP exposure suppressed the PPARα -mediated lipid metabolic pathway, leading to a systemic imbalance in lipid homeostasis within the skin tissue. Interestingly, PS-MPs specifically triggered dysregulation in DNA replication and cell cycle-related signaling. In vitro assays demonstrated that PS-NPs could penetrate HaCaT cells and accumulate in lysosomes and cell membranes, exerting dose-dependent cytotoxicity. Conversely, PS-MPs primarily resided in the intercellular spaces and exhibited lower toxicity. Our findings demonstrate that maternal PS-MNP exposure compromises offspring skin barrier integrity by interfering with PPARα -mediated lipid metabolism. This study provides critical evidence for the health risks of maternal MNPs exposure on neonatal skin development, and identifies potential biomarkers for MNPs-induced cutaneous toxicity.