Placenta and fetal brain share a neurodevelopmental disorder DNA methylation profile in a mouse model of prenatal PCB exposure
| Autor: | Benjamin I. Laufer, Kari Neier, Anthony E. Valenzuela, Dag H. Yasui, Rebecca J. Schmidt, Pamela J. Lein, Janine M. LaSalle |
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| Rok vydání: | 2022 |
| Předmět: |
placenta
polychlorinated biphenyls Placenta autism spectrum disorders brain Intellectual and Developmental Disabilities (IDD) Medical Physiology Reproductive health and childbirth General Biochemistry Genetics and Molecular Biology Mice Rett syndrome Pregnancy Genetics Animals PCBs reproductive and urinary physiology MeCP2 Pediatric DNA methylation epigenetics neurodevelopmental disorders Prevention Neurosciences Brain DNA Methylation Polychlorinated Biphenyls Brain Disorders Neurodevelopmental Disorders embryonic structures Female Biochemistry and Cell Biology whole-genome bisulfite sequencing |
| Zdroj: | Cell reports, vol 38, iss 9 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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