Sex Differences in the Effects of Prenatal Bisphenol A Exposure on Genes Associated with Autism Spectrum Disorder in the Hippocampus

In this study, we investigated the prenatal effects of bisphenol-A (BPA) exposure on transcriptome profiles in the hippocampus of the rat offspring. Transcriptome profiling by RNA-seq analysis of hippocampi isolated from neonatal pups prenatally exposed to BPA was conducted and revealed a list of differentially expressed genes (DEGs) associated with ASD. Among the DEGs, several ASD candidate genes, including Auts2 and Foxp2, were dysregulated and showed sex differences in response to BPA exposure. The interactome and pathway analyses of DEGs revealed significant associations between the DEGs in males and neurological functions/disorders associated with ASD. The findings from this study indicate that prenatal BPA exposure alters the expression of ASD-linked genes in the hippocampus and suggest that maternal BPA exposure may increase ASD susceptibility by dysregulating genes associated with neurological functions known to be negatively impacted in ASD. Overall design: We conducted experiments using the neonatal rat hippocampus maternally exposed to BPA or vehicle control (BPA treament; pooled 3 hippocampi, vehicle control; pooled 3 hippocampi). 10-week-old female rats were daily treated with BPA at the concentration of 5,000 µg/kg·BW or vehicle control from gestation day 1 (GD1) until parturition. RNA was isolated and cDNA was synthesized. The transcriptome profiles was performed using a high-throughtput RNA-seq.