The Ph.D. Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Sci Rep. 2019 Feb 28;9(1):3038. doi: 10.1038/s41598-019-39386-w.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder inexplicably biased towards males. Although prenatal exposure to bisphenol A (BPA) has recently been associated with the ASD risk, whether BPA dysregulates ASD-related genes in the developing brain remains unclear. In this study, 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 using Ingenuity Pathway Analysis software revealed significant associations between the DEGs in males and neurological functions/disorders associated with ASD. Moreover, the reanalysis of transcriptome profiling data from previously published BPA studies consistently showed that BPA-responsive genes were significantly associated with ASD-related genes. 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, which deserves further investigations.
自闭症谱系障碍（ASD）是一种神经发育障碍，男性明显易患。虽然最近有研究表明产前暴露于双酚 A（BPA）与 ASD 风险相关，但 BPA 是否会在发育中的大脑中扰乱与 ASD 相关的基因仍不清楚。在这项研究中，通过对产前暴露于 BPA 的新生幼鼠海马组织的 RNA-seq 分析进行转录组谱分析，揭示了与 ASD 相关的一组差异表达基因（DEG）。在 DEG 中，一些 ASD 候选基因，包括 Auts2 和 Foxp2，受到 BPA 暴露的调控，并表现出性别差异。使用 IPA 软件对 DEG 的互作网络和通路分析显示，雄性中 DEG 与与 ASD 相关的神经功能/疾病之间存在显著关联。此外，对先前发表的 BPA 研究中的转录组谱数据的重新分析表明，BPA 反应基因与 ASD 相关基因显著相关。这项研究的结果表明，产前 BPA 暴露会改变海马体中与 ASD 相关基因的表达，并表明母体 BPA 暴露可能通过扰乱与神经功能相关的基因来增加 ASD 的易感性，这些基因在 ASD 中受到负面影响，值得进一步研究。
