Placenta and fetal brain share a neurodevelopmental disorder DNA methylation profile in a mouse model of prenatal PCB exposure

Benjamin I. Laufer, Kari Neier, Anthony E. Valenzuela, Dag H. Yasui, Rebecca J. Schmidt, Pamela J. Lein, Janine M. LaSalle

Research output: Contribution to journalArticlepeer-review

Abstract

Polychlorinated biphenyls (PCBs) are developmental neurotoxicants implicated as environmental risk factors for neurodevelopmental disorders (NDDs). Here, we report the effects of prenatal exposure to a human-relevant mixture of PCBs on the DNA methylation profiles of mouse placenta and fetal brain. Thousands of differentially methylated regions (DMRs) distinguish placenta and fetal brain from PCB-exposed mice from sex-matched vehicle controls. In both placenta and fetal brain, PCB-associated DMRs are enriched for functions related to neurodevelopment and cellular signaling and enriched within regions of bivalent chromatin. The placenta and brain PCB DMRs overlap significantly and map to a shared subset of genes enriched for Wnt signaling, Slit/Robo signaling, and genes differentially expressed in NDD models. The consensus PCB DMRs also significantly overlap with DMRs from human NDD brain and placenta. These results demonstrate that PCB-exposed placenta contains a subset of DMRs that overlap fetal brain DMRs relevant to an NDD.

Original languageEnglish (US)
Article number110442
JournalCell Reports
Volume38
Issue number9
DOIs
StatePublished - Mar 1 2022

Keywords

  • autism spectrum disorders
  • brain
  • DNA methylation
  • epigenetics
  • MeCP2
  • neurodevelopmental disorders
  • PCBs
  • placenta
  • polychlorinated biphenyls
  • Rett syndrome
  • whole-genome bisulfite sequencing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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