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Tissue and sex-specific programming of DNA methylation by perinatal lead exposure: implications for environmental epigenetics studies.

Authors
  • Svoboda, Laurie K1
  • Neier, Kari1
  • Wang, Kai2
  • Cavalcante, Raymond G3
  • Rygiel, Christine A1
  • Tsai, Zing1, 2
  • Jones, Tamara R1
  • Liu, Siyu2
  • Goodrich, Jaclyn M1
  • Lalancette, Claudia3
  • Colacino, Justin A1, 4
  • Sartor, Maureen A2, 5
  • Dolinoy, Dana C1, 4
  • 1 Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA.
  • 2 Department of Computational Medicine and Bioinformatics, University of Michigan Medical School Palmer Commons, Ann Arbor, MI, USA.
  • 3 Epigenomics Core, University of Michigan, Medical School, Ann Arbor, MI, USA.
  • 4 Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA.
  • 5 Department of Biostatistics, University of Michigan, School of Public Health, Ann Arbor, MI, USA.
Type
Published Article
Journal
Epigenetics
Publisher
Landes Bioscience
Publication Date
Oct 01, 2021
Volume
16
Issue
10
Pages
1102–1122
Identifiers
DOI: 10.1080/15592294.2020.1841872
PMID: 33164632
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Early developmental environment can influence long-term health through reprogramming of the epigenome. Human environmental epigenetics studies rely on surrogate tissues, such as blood, to assess the effects of environment on disease-relevant but inaccessible target tissues. However, the extent to which environment-induced epigenetic changes are conserved between these tissues is unclear. A better understanding of this conservation is imperative for effective design and interpretation of human environmental epigenetics studies. The Toxicant Exposures and Responses by Genomic and Epigenomic Regulators of Transcription (TaRGET II) consortium was established by the National Institute of Environmental Health Sciences to address the utility of surrogate tissues as proxies for toxicant-induced epigenetic changes in target tissues. We and others have recently reported that perinatal exposure to lead (Pb) is associated with adverse metabolic outcomes. Here, we investigated the sex-specific effects of perinatal exposure to a human environmentally relevant level of Pb on DNA methylation in paired liver and blood samples from adult mice using enhanced reduced-representation bisulphite sequencing. Although Pb exposure ceased at 3 weeks of age, we observed thousands of sex-specific differentially methylated cytosines in the blood and liver of Pb-exposed animals at 5 months of age, including 44 genomically imprinted loci. We observed significant tissue overlap in the genes mapping to differentially methylated cytosines. A small but significant subset of Pb-altered genes exhibit basal sex differences in gene expression in the mouse liver. Collectively, these data identify potential molecular targets for Pb-induced metabolic diseases, and inform the design of more robust human environmental epigenomics studies.

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