Sex Differences in the Effects of Prenatal Bisphenol A Exposure on Genes Associated with Autism Spectrum Disorder in the Hippocampus.
Sex Differences in the Effects of Prenatal Bisphenol A Exposure on Genes Associated with Autism Spectrum Disorder in the Hippocampus.
复制标题
产前双酚 A 暴露对海马自闭症谱系障碍相关基因影响的性别差异。
DOI：
10.1038/s41598-019-39386-w
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发表时间：
2019
影响因子：
4.6
通讯作者：
Sarachana,Tewarit
中科院分区：
文献类型：
--
作者：
Thongkorn,Surangrat;Kanlayaprasit,Songphon;Jindatip,Depicha;Tencomnao,Tewin;Hu,ValerieW;Sarachana,Tewarit
自闭症谱系障碍（ASD）是一种神经发育障碍，令人费解地偏向于男性。虽然产前接触双酚A（BPA）最近与ASD风险有关，但BPA是否会使发育中的大脑中ASD相关基因失调仍不清楚。在这项研究中，通过RNA-seq分析对从产前暴露于BPA的新生幼崽中分离的Eschampi进行了转录组分析，并揭示了与ASD相关的差异表达基因（DEG）列表。在DEG中，几个ASD候选基因，包括Auts 2和Foxp 2，在BPA暴露的反应中表现出失调和性别差异。DEG的相互作用组和通路分析使用Incidity Pathway Analysis软件揭示了男性DEG与ASD相关的神经功能/疾病之间的显著相关性。此外，对先前发表的BPA研究的转录组分析数据的重新分析一致表明，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暴露改变了海马中ASD相关基因的表达，并表明母体BPA暴露可能通过与ASD中已知受到负面影响的神经功能相关的基因失调来增加ASD易感性，这值得进一步研究。
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, includingAuts2andFoxp2, 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.