Transgenerational transmission of neurodevelopmental disorders induced by maternal exposure to PM2.5

Abstract

The pathological traits or diseases susceptibility caused by maternal exposure to environmental adverse insults (infection, malnutrition, environmental toxicants) could be transmitted across generations. It remains uncertain, however, whether the neurodevelopmental disturbances of offspring induced by maternal exposure to PM2.5 during early life can be inherited by subsequent generations without further exposure. In the current study, using transgenerational animal models, we found that F1 female showed poorer performance in Morris Water Maze (MWM), and the deficits in spatial learning and memory similarly presented in F2-F3 female. The transgenerationally-transmitted neurobehavioral disorders were mediated both via maternal and paternal lineage. Since the epigenetic modifications have been reported to be involved in the disturbed neurodevelopment induced by maternal exposure to detrimental environmental factors during early life, we further explored the possible epigenetic mechanism of the transgenerational effects. Intriguingly, the results displayed the significant increase in expression of Dnmt3a in F1 female offspring. And the hypermethylation of Bdnf promoter Ⅳ and downregulated expression of Bdnf in hippocampus were stably transmitted across the generations until the third generation. There was another interesting finding that the transgenerational effects were sex-specific and only emerged in female offspring. Together, our study indicated for the first time that maternal exposure to PM2.5 during early life could detrimentally affect neurobehaviors in multiple generations, and the declined expression of Bdnf induced by hypermethylation of Bdnf promoter Ⅳ mediated by Dnmts might be the potential molecular mechanism.

Keywords: Neurodevelopmental disorders; PM2.5; Transgenerational effects.