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

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

Research output: Contribution to journal › Article › peer-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 language	English (US)
Article number	110442
Journal	Cell Reports
Volume	38
Issue number	9
DOIs	https://doi.org/10.1016/j.celrep.2022.110442
State	Published - 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)

Access to Document

10.1016/j.celrep.2022.110442

Cite this

Placenta and fetal brain share a neurodevelopmental disorder DNA methylation profile in a mouse model of prenatal PCB exposure. / Laufer, Benjamin I.; Neier, Kari; Valenzuela, Anthony E.; Yasui, Dag H.; Schmidt, Rebecca J.; Lein, Pamela J.; LaSalle, Janine M.

In: Cell Reports, Vol. 38, No. 9, 110442, 01.03.2022.

Research output: Contribution to journal › Article › peer-review

@article{83388c83af10453fbddbc179d0d7a398,

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

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

author = "Laufer, {Benjamin I.} and Kari Neier and Valenzuela, {Anthony E.} and Yasui, {Dag H.} and Schmidt, {Rebecca J.} and Lein, {Pamela J.} and LaSalle, {Janine M.}",

note = "Funding Information: This work was supported by a National Institutes of Health (NIH) grant ( R01ES029213 ) to J.M.L., P.J.L., and R.J.S.; a Canadian Institutes of Health Research (CIHR) Banting postdoctoral fellowship ( BPF-162684 ) to B.I.L.; a NIH postdoctoral fellowship ( F32HD105325 ) to K.N.; and the UC Davis Intellectual and Developmental Disabilities Research Center (IDDRC) ( P50HD103526 ). The library preparation and sequencing was carried out by the DNA Technologies and Expression Analysis Cores at the UC Davis Genome Center and was supported by a NIH Shared Instrumentation Grant ( 1S10OD010786-01 ). The synthesis of the PCB mixture was supported by the Superfund Research Center at The University of Iowa ( P42 ES013661 ). We also thank Dr. Kimberly Keil Stietz and Dr. Annie Ciernia for input related to the mouse work. Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = mar,

day = "1",

doi = "10.1016/j.celrep.2022.110442",

language = "English (US)",

volume = "38",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "9",

}

TY - JOUR

T1 - Placenta and fetal brain share a neurodevelopmental disorder DNA methylation profile in a mouse model of prenatal PCB exposure

AU - Laufer, Benjamin I.

AU - Neier, Kari

AU - Valenzuela, Anthony E.

AU - Yasui, Dag H.

AU - Schmidt, Rebecca J.

AU - Lein, Pamela J.

AU - LaSalle, Janine M.

N1 - Funding Information: This work was supported by a National Institutes of Health (NIH) grant ( R01ES029213 ) to J.M.L., P.J.L., and R.J.S.; a Canadian Institutes of Health Research (CIHR) Banting postdoctoral fellowship ( BPF-162684 ) to B.I.L.; a NIH postdoctoral fellowship ( F32HD105325 ) to K.N.; and the UC Davis Intellectual and Developmental Disabilities Research Center (IDDRC) ( P50HD103526 ). The library preparation and sequencing was carried out by the DNA Technologies and Expression Analysis Cores at the UC Davis Genome Center and was supported by a NIH Shared Instrumentation Grant ( 1S10OD010786-01 ). The synthesis of the PCB mixture was supported by the Superfund Research Center at The University of Iowa ( P42 ES013661 ). We also thank Dr. Kimberly Keil Stietz and Dr. Annie Ciernia for input related to the mouse work. Publisher Copyright: © 2022 The Authors

PY - 2022/3/1

Y1 - 2022/3/1

N2 - 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.

AB - 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.

KW - autism spectrum disorders

KW - brain

KW - DNA methylation

KW - epigenetics

KW - MeCP2

KW - neurodevelopmental disorders

KW - PCBs

KW - placenta

KW - polychlorinated biphenyls

KW - Rett syndrome

KW - whole-genome bisulfite sequencing

UR - http://www.scopus.com/inward/record.url?scp=85125275485&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85125275485&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2022.110442

DO - 10.1016/j.celrep.2022.110442

M3 - Article

C2 - 35235788

AN - SCOPUS:85125275485

VL - 38

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 9

M1 - 110442

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this