Prenatal environmental stressors impair postnatal microglia function and adult behavior in males

Gestational exposure to environmental toxins and socioeconomic stressors is epidemiologically linked to neurodevelopmental disorders with strong male bias, such as autism. We model these prenatal risk factors in mice by co-exposing pregnant dams to an environmental pollutant and limited-resource stress, which robustly activates the maternal immune system. Only male offspring display long-lasting behavioral abnormalities and alterations in the activity of brain networks encoding social interactions. Cellularly, prenatal stressors diminish microglial function within the anterior cingulate cortex, a central node of the social coding network, in males during early postnatal development. Precise inhibition of microglial phagocytosis within the anterior cingulate cortex (ACC) of wild-type (WT) mice during the same critical period mimics the impact of prenatal stressors on a male-specific behavior, indicating that environmental stressors alter neural circuit formation in males via impairing microglia function during development. [Display omitted] •Prenatal exposure to air pollution and stress (DEP + MS) induces MIA•DEP + MS induces social/communication and circuit deficits in male offspring•DEP + MS impairs microglial pruning of developing thalamocortical synapses•Inhibition of microglial phagocytosis phenocopies social deficits observed in DEP + MS Block et al. show that combined exposure to air pollution and maternal stress during pregnancy activates the maternal immune system and induces male-specific impairments in social behavior and circuit connectivity in offspring. Cellularly, prenatal stressors diminish microglia phagocytic function, and inhibition of microglia phagocytosis phenocopies behavioral deficits from prenatal stressors.