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.本研究探究了双酚A（bisphenol-A, BPA）暴露对大鼠后代海马体转录组谱的产前影响。本研究对产前暴露于BPA的新生幼鼠海马体进行分离后，开展RNA测序（RNA-seq）转录组分析，最终鉴定出一批与孤独症谱系障碍（Autism Spectrum Disorder, ASD）相关的差异表达基因（differentially expressed genes, DEGs）。在这批差异表达基因中，包括Auts2、Foxp2在内的多个孤独症谱系障碍候选基因出现表达失调，且其对BPA暴露的响应存在性别差异。对上述差异表达基因的相互作用组与通路分析显示，雄性个体中的差异表达基因与孤独症谱系障碍相关的神经功能及神经紊乱存在显著关联。本研究结果表明，产前BPA暴露可改变大鼠海马体内与孤独症谱系障碍相关的基因表达，同时提示母体BPA暴露或可通过失调孤独症谱系障碍中功能受损的神经功能相关基因，提升子代的孤独症谱系障碍易感性。