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

doi:10.1016/j.celrep.2022.110442

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

Cell Rep. 2022 Mar 1;38(9):110442. doi: 10.1016/j.celrep.2022.110442.

Authors

Benjamin I Laufer¹, Kari Neier², Anthony E Valenzuela³, Dag H Yasui¹, Rebecca J Schmidt⁴, Pamela J Lein⁵, Janine M LaSalle⁶

Affiliations

¹ Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, CA 95616, USA; UC Davis Genome Center, University of California, Davis, Davis, CA 95616, USA; MIND Institute, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.
² Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, CA 95616, USA; UC Davis Genome Center, University of California, Davis, Davis, CA 95616, USA; MIND Institute, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA; Perinatal Origins of Disparities Center, University of California, Davis, Davis, CA 95616, USA.
³ Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.
⁴ MIND Institute, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA; Perinatal Origins of Disparities Center, University of California, Davis, Davis, CA 95616, USA; Department of Public Health Sciences, School of Medicine, University of California, Davis, Davis, CA 95616, USA.
⁵ MIND Institute, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA; Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.
⁶ Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, CA 95616, USA; UC Davis Genome Center, University of California, Davis, Davis, CA 95616, USA; MIND Institute, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA; Perinatal Origins of Disparities Center, University of California, Davis, Davis, CA 95616, USA. Electronic address: jmlasalle@ucdavis.edu.

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.

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

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain
DNA Methylation / genetics
Female
Mice
Neurodevelopmental Disorders* / genetics
Placenta
Polychlorinated Biphenyls* / toxicity
Pregnancy

Substances

Polychlorinated Biphenyls

Abstract

Publication types

MeSH terms

Substances

Grants and funding