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. 2019 Feb 28;9(1):3038.
doi: 10.1038/s41598-019-39386-w.

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

Surangrat Thongkorn  1 , Songphon Kanlayaprasit  1 , Depicha Jindatip  2 , Tewin Tencomnao  3 , Valerie W Hu  4 , Tewarit Sarachana  5
Affiliations

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

Surangrat Thongkorn et al. Sci Rep. .

Abstract

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
The regulatory network of DEGs in hippocampal tissues is related to neurological diseases/disorders and functions that are impacted in ASD. The gene regulatory network was predicted by IPA software using the list of DEGs from RNA-seq (colored; red = up-regulation; green = down-regulation), and the IPA showed that these genes are associated with functions that are impacted in individuals with ASD. (A) male (B) female.
Figure 2
Figure 2
Box plot of ASD-related gene expression in hippocampal tissues. The expression levels of Auts2 (A), Foxp2 (B), Smarcc2 (C), and Dicer1 (D) were determined in both sexes and separately in males and females. The qRT-PCR analyses revealed that Auts2 and Foxp2 were significantly down-regulated in the hippocampi of both sexes and males that were prenatally exposed to BPA. In contrast, Smarcc2 was significantly reduced in both sexes and in females, and Dicer1 was significantly reduced in both sexes. * P-value < 0.05.
See this image and copyright information in PMC

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