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Sci Rep. 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.

Author information

1
The Ph.D. Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
2
Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
3
Age-related Inflammation and Degeneration Research Unit, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
4
Department of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA.
5
Age-related Inflammation and Degeneration Research Unit, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand. tewarit.sa@chula.ac.th.

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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