Prenatal exposure to environmental toxins induces sexually dimorphic transcriptome changes in neonatal offspring

Purpose: Gestational exposure to environmental toxins and socioeconomic stressors are epidemiologically linked to neurodevelopmental disorders with strong male-bias, such as autism. We modeled these prenatal risk factors in mice, by co-exposing pregnant dams to an environmental pollutant and limited-resource stress, which robustly activated the maternal immune system. Only male offspring displayed long-lasting behavioral abnormalities and alterations in the activity of brain networks encoding social interactions. Cellularly, prenatal stressors diminished microglial function within the anterior cingulate cortex, a central node of the social coding network, in males during early postnatal development. Genetic ablation of microglia during the same critical period mimicked 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. Methods: Pregnant dams were exposed with either CON or DEP+MS, at P8 prefrontal cortices of male and female offspring born to exposed mothers were collected and RNA was extracted. . RNA-seq libraries were prepared using the commercially available KAPA Stranded mRNA-Seq Kit. Sequencing was performed on an Illumina NovaSeq 6000 using S-Prime flow cell at 50bp paired-end