Autism-related transcription factors underlying the sex-specific effects of prenatal bisphenol a exposure on transcriptome-interactome profiles in the offspring prefrontal cortex

Songphon Kanlayaprasit, Surangrat Thongkorn, Pawinee Panjabud, Depicha Jindatip, Valerie W. Hu, Takako Kikkawa, Noriko Osumi, Tewarit Sarachana

Research output: Contribution to journalArticlepeer-review

Abstract

Bisphenol A (BPA) is an environmental risk factor for autism spectrum disorder (ASD). BPA exposure dysregulates ASD-related genes in the hippocampus and neurological functions of offspring. However, whether prenatal BPA exposure has an impact on genes in the prefrontal cortex, another brain region highly implicated in ASD, and through what mechanisms have not been investigated. Here, we demonstrated that prenatal BPA exposure disrupts the transcriptome–interactome profiles of the prefrontal cortex of neonatal rats. Interestingly, the list of BPA-responsive genes was significantly enriched with known ASD candidate genes, as well as genes that were dysregulated in the postmortem brain tissues of ASD cases from multiple independent studies. Moreover, several differentially expressed genes in the offspring’s prefrontal cortex were the targets of ASD-related transcription factors, including AR, ESR1, and RORA. The hypergeometric distribution analysis revealed that BPA may regulate the expression of such genes through these transcription factors in a sex-dependent manner. The molecular docking analysis of BPA and ASD-related transcription factors revealed novel potential targets of BPA, including RORA, SOX5, TCF4, and YY1. Our findings indicated that prenatal BPA exposure disrupts ASD-related genes in the offspring’s prefrontal cortex and may increase the risk of ASD through sex-dependent molecular mechanisms, which should be investigated further.

Original languageEnglish
Article number13201
JournalInternational journal of molecular sciences
Volume22
Issue number24
DOIs
Publication statusPublished - 2021 Dec 1

Keywords

  • Autism spectrum disorder
  • Bisphenol A
  • Endocrine-disrupting chemical
  • Interactome
  • Molecular docking
  • Prefrontal cortex
  • Prenatal exposure
  • Sex differences
  • Transcription factor
  • Transcriptome

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint

Dive into the research topics of 'Autism-related transcription factors underlying the sex-specific effects of prenatal bisphenol a exposure on transcriptome-interactome profiles in the offspring prefrontal cortex'. Together they form a unique fingerprint.

Cite this