Gestational exposure to PM2.5 is associated with adverse postnatal outcomes.PM2.5 can enter alveoli by using intratracheal instillation,even penetrate through lung cells into the blood circulation.Subsequently,they are transferred across the placenta and fetal blood brain barrier,causing the adverse birth outcomes of offspring.This study demonstrated that the gestational exposure resulted in cognitive and emotional disorders in female offspring although the offspring were not exposed to PM2,5.Placental metabolic pathways modulated fetal brain development and played a pivotal role for maternal-placental-fetal interactions in the fetal programming of adult behavioral and mental disorders.Samples of fetus,offspring hippocampus and placenta from the mice exposed to PM2.5 were investigated using a compre-hensive approach including mass spectrometry-based lipidomics and three-dimensional imaging.The exposure induced the neuro-degeneration in hippocampus,impairment of placental cytoarchitecture,and reprogramming of lipidome,which might affect the modulation of maternal-fetal cross-talk and result in the behavior disorders of offspring.The variation of spatial distribution of lipids was profoundly affected in dorsal pallium and hippocampal formation regions of fetal brain,offspring hippocampus,as well as labyrinth and junctional zones of placenta.The abundance alteration of lipid markers associated with neurodegenerative diseases was validated in transgenic mouse model with Alzheimer's disease and human cerebrospinal fluid from patients with Parkinson's disease.The finding could help with the selec-tion of more suitable heterogeneous-related substructures targeting PM2.5 exposure and the exploration of PM2.5-induced toxicological effects on neurodegenerative diseases.