Early-life exposure to polypropylene nanoplastics induces neurodevelopmental toxicity in mice and human iPSC-derived cerebral organoids

Nanoplastics (NPs) are emerging environmental pollutants that pose growing concerns due to their potential health risks. However, the effects of inhaled NP exposure during pregnancy on fetal brain development remain poorly understood. In this study, we investigated the impact of maternal exposure to polypropylene nanoplastics (PP-NPs) on fetal brain development and neurobehavioral outcomes in a mouse model and further explored its mechanism in human cerebral organoids. Maternal exposure to PP-NPs significantly impaired neuronal differentiation and proliferation in the fetal cortex. Neurobehavioral assessments revealed significant deficits in offspring following maternal exposure, including impaired spatial memory, reduced motor coordination, and heightened anxiety-like behavior. Furthermore, human brain organoids exposed to PP-NPs exhibited reduced growth and neuronal differentiation, with significant downregulation of key neuronal markers such as TUJ1, MAP2, and PAX6. Transcriptomic analysis identified alterations in gene expression, particularly in neuroactive ligand-receptor interaction pathway. Molecular docking and fluorescence co-localization analysis further suggested CYSLTR1 and PTH1R as key molecular targets of PP-NPs. These findings provide novel insights into the toxicological effects of NPs on the developing brain and emphasize the need for preventive measures to protect fetal neurodevelopment during pregnancy.