Prenatal and Lactational Exposure to Polystyrene Nanoplastics Induces Lipid Accumulation in Vascular Smooth Muscle Cells of Male Offspring via the MAPK/ERK/UHRF1 Signaling Pathway

Nanoplastics (NPs) have been shown to cross the placental barrier and disrupt systemic metabolism, raising concerns about their potential impact on developmental health. Despite accumulating evidence implicating NPs in metabolic toxicity, the effect of early-life NPs exposure on offspring vascular lipid metabolism has not been fully elucidated. In this study, pregnant mice were exposed to 100-nm PS-NPs at drinking-water concentrations of 0.1, 1, and 10 µg/mL throughout embryonic-lactational, and male offspring were examined at postnatal day 21. Our findings demonstrated that exposure to PS-NPs during the embryonic and lactational periods induced lipid accumulation in the medial layer of the aorta in male offspring, accompanied by elevated serum triglyceride (TG) levels, suggesting that early-life exposure disrupts vascular lipid homeostasis. In vitro findings further confirmed that PS-NPs exposure led to lipid accumulation in mouse aortic vascular smooth muscle (MOVAS) cells, accompanied by elevated intracellular TG levels. Mechanistically, PS-NPs exposure activated the MAPK/ERK signaling pathway, accompanied by the upregulation of UHRF1, a key epigenetic regulator of lipid metabolism. Further pharmacological inhibition of ERK using PD98059 significantly attenuated both UHRF1 expression and lipid accumulation, providing additional evidence supporting the critical role of the MAPK/ERK/UHRF1 axis in PS-NPs-induced lipid dysregulation. Additionally, siRNA-mediated knockdown of UHRF1 alleviated PS-NPs-induced lipid accumulation, supporting the pivotal role of UHRF1 in the cellular response to PS-NPs exposure. Overall, these findings demonstrate that prenatal and lactational exposure to PS-NPs disrupts early vascular lipid homeostasis in male offspring by activating the MAPK/ERK/UHRF1 signaling pathway in vascular smooth muscle cells.