Maternal exposure to PM2.5 impairs behaviors and hippocampal plasticity in association with reduced cysteine levels in adult offspring

Autism spectrum disorder (ASD) is characterized by early-onset challenges in social communication and repetitive behaviors, influenced by both genetic and environmental factors. The global increase in ASD diagnoses has drawn attention to air pollution as a significant environmental risk factor, although the underlying mechanisms remain unclear. This study investigates the impact of maternal exposure to the air pollutant PM _2.5 on ASD risk in offspring. In this study, female C57BL/6J mice were exposed to PM _2.5 via intratracheal instillation every three days for two weeks prior to mating, with exposure continuing until birth. Both male and female offspring exhibited reduced social novelty and increased repetitive behaviors, only male offspring showed significant impairment in working memory. PM _2.5 exposure led to an increased number of proliferating progenitor cells and immature neurons in the hippocampus of male offspring, a change not observed in females. However, PM _2.5 exposure resulted in reduced dendritic length exclusively in female offspring, while both sexes experienced decreased long-term potentiation and synaptic GluN2B protein expression. These structural changes were associated with significantly lower cysteine levels in the hippocampi of offspring of both sexes, but not with changes in relative abundance of gut microbiota and neuroinflammatory response in the hippocampus. These findings suggest that maternal PM _2.5 exposure may induce autism-like behaviors in offspring, potentially linked to reduced hippocampal cysteine levels and hippocampal dysfunction.