Maternal exposure to polypropylene nanoplastics disrupts sex- and region-specific lipid metabolism in the brains of C57BL/6N mouse offspring.

Polypropylene nanoplastics (PPNPs), produced through the degradation of widely used plastic products, are increasingly recognized as emerging environmental contaminants with potential neurodevelopmental toxicity. However, the long-term biochemical consequences of prenatal PPNP exposure on brain development remain poorly understood. In this study, we performed a region- and sex-specific targeted lipidomic analysis to examine how maternal oral exposure to PPNPs during pregnancy and lactation alters brain lipid composition in offspring at postnatal day 21. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we profiled lipid classes in the hippocampus (HP), cortex (CTX), cerebellum (CB), and dorsal raphe nucleus (DR) of both male and female mice. Our findings revealed distinct, region-specific lipid remodeling patterns in response to PPNP exposure. Females exhibited consistent reductions in neuroprotective lipids, including lysophosphatidylethanolamines (LPEs) and plasmalogens, most prominently in the hippocampus. Males, in contrast, displayed elevated triglyceride levels and region-specific alterations in phospholipid composition, such as reduced phosphatidylcholines in the hippocampus and dorsal raphe. These results indicate that maternal nanoplastic exposure, even without postnatal contact, can cause persistent, sex-specific disturbances in brain lipid metabolism. To our knowledge, this study provides the first targeted lipidomic characterization of offspring brains following maternal PPNP exposure and highlights the importance of brain region-specific lipid analysis for identifying localized disruptions in neurodevelopment caused by environmental pollutants.