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Environ Health. 2019 Feb 28;18(1):18. doi: 10.1186/s12940-019-0455-9.

Prenatal arsenic exposure alters the placental expression of multiple epigenetic regulators in a sex-dependent manner.

Author information

1
Molecular Oncology Program, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. emily.winterbottom@gmail.com.
2
Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, 03755, USA.
3
Pulmonary and Critical Care Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, 03756, USA.
4
Molecular Oncology Program, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
5
Center for Therapeutic Innovation, Department of Psychiatry and Behavioral Sciences, The Miami Project to Cure Paralysis, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL, 33136, USA.
6
Department of Environmental Health, Rollins School of Public Health at Emory University, Atlanta, GA, 30322, USA.
7
Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, 03755, USA. Margaret.R.Karagas@dartmouth.edu.

Abstract

BACKGROUND:

Prenatal exposure to arsenic has been linked to a range of adverse health conditions in later life. Such fetal origins of disease are frequently the result of environmental effects on the epigenome, leading to long-term alterations in gene expression. Several studies have demonstrated effects of prenatal arsenic exposure on DNA methylation; however the impact of arsenic on the generation and decoding of post-translational histone modifications (PTHMs) is less well characterized, and has not been studied in the context of prenatal human exposures.

METHODS:

In the current study, we examined the effect of exposure to low-to-moderate levels of arsenic in a US birth cohort, on the expression of 138 genes encoding key epigenetic regulators in the fetal portion of the placenta. Our candidate genes included readers, writers and erasers of PTHMs, and chromatin remodelers.

RESULTS:

Arsenic exposure was associated with the expression of 27 of the 138 epigenetic genes analyzed. When the cohort was stratified by fetal sex, arsenic exposure was associated with the expression of 40 genes in male fetal placenta, and only 3 non-overlapping genes in female fetal placenta. In particular, we identified an inverse relationship between arsenic exposure and expression of the gene encoding the histone methyltransferase, PRDM6 (pā€‰<ā€‰0.001). Mutation of PRDM6 has been linked to the congenital heart defect, patent ductus arteriosus.

CONCLUSIONS:

Our findings suggest that prenatal arsenic exposure may have sex-specific effects on the fetal epigenome, which could plausibly contribute to its subsequent health impacts.

KEYWORDS:

Arsenic; Epigenetic; Fetal placenta; Histones; PRDM6; Prenatal; Sex

PMID:
30819207
PMCID:
PMC6396530
DOI:
10.1186/s12940-019-0455-9
[Indexed for MEDLINE]
Free PMC Article

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