Maternal exposure to PM2.5 induces cognitive impairment in offspring via cerebellar neuroinflammation and oxidative stress

Available evidence suggest that exposure to PM2.5 during pregnancy is associated with reduced cognitive function in offspring. This study aimed to investigate the effects of maternal exposure to PM2.5 on offspring cognitive function and to elucidate the underlying mechanisms. In this work, pregnant C57BL/6 female mice were exposed to concentrated ambient PM2.5 or filtered air from day 0.5 (=vaginal plug) to day 15.5 in the Shanghai Meteorological and Environmental Animal Exposure System, and offspring cerebellar tissues were collected on embryonic day 15.5, as well as postnatal days 0, 10 and 42. The mean PM2.5 concentrations exposed to the pregnant mice were 73.06 ± 4.90 μg/m3 and 11.15 ± 2.71 μg/m3 in the concentrated ambient PM2.5 and filtered air chambers, respectively. Maternal concentrated PM2.5 exposure was negatively correlated with offspring spatial memory significantly as assessed by the Morris water maze. Compared with the filtered air group, PM2.5-exposed offspring mice had reduced cerebellar microglia. Both RNA and protein levels of IL-8 and TNF-α were elevated in the concentrated ambient PM2.5 group. PM2.5 exposure increased the level of 8-OHG in miRNA of microglia and Purkinje cells in 6-week-old offspring. The level of prostaglandin F2α (8-iso-PGF2Aα) in the cerebellum was increased at different growing stages of offspring after gestational exposure of PM2.5. These results suggested that maternal air pollution exposure might cause inflammatory damage and oxidative stress to the cerebellum, contributing to reduced cognitive performance in mice offspring.