Prenatal arsenic exposure alters the placental expression of multiple epigenetic regulators in a sex-dependent manner 06 Biological Sciences 0604 Genetics 11 Medical and Health Sciences 1114 Paediatrics and Reproductive Medicine

Emily F. Winterbottom, Yuka Moroishi, Yuliya Halchenko, David A. Armstrong, Paul J. Beach, Quang P. Nguyen, Anthony J Capobianco, Nagi Ayad, Carmen J. Marsit, Zhigang Li, Margaret R. Karagas, David J Robbins

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 (p < 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.

Original languageEnglish (US)
Article number18
JournalEnvironmental Health: A Global Access Science Source
Volume18
Issue number1
DOIs
StatePublished - Feb 28 2019

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Reproductive Medicine
Biological Science Disciplines
Medical Genetics
Arsenic
Epigenomics
Pediatrics
Health
Histone Code
Placenta
Gene Expression
Post Translational Protein Processing
Genes
Fetal Diseases
Patent Ductus Arteriosus
Congenital Heart Defects
DNA Methylation
Chromatin
Parturition
Mutation

Keywords

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

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Cite this

Prenatal arsenic exposure alters the placental expression of multiple epigenetic regulators in a sex-dependent manner 06 Biological Sciences 0604 Genetics 11 Medical and Health Sciences 1114 Paediatrics and Reproductive Medicine. / Winterbottom, Emily F.; Moroishi, Yuka; Halchenko, Yuliya; Armstrong, David A.; Beach, Paul J.; Nguyen, Quang P.; Capobianco, Anthony J; Ayad, Nagi; Marsit, Carmen J.; Li, Zhigang; Karagas, Margaret R.; Robbins, David J.

In: Environmental Health: A Global Access Science Source, Vol. 18, No. 1, 18, 28.02.2019.

Research output: Contribution to journalArticle

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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 (p < 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.",
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T1 - Prenatal arsenic exposure alters the placental expression of multiple epigenetic regulators in a sex-dependent manner 06 Biological Sciences 0604 Genetics 11 Medical and Health Sciences 1114 Paediatrics and Reproductive Medicine

AU - Winterbottom, Emily F.

AU - Moroishi, Yuka

AU - Halchenko, Yuliya

AU - Armstrong, David A.

AU - Beach, Paul J.

AU - Nguyen, Quang P.

AU - Capobianco, Anthony J

AU - Ayad, Nagi

AU - Marsit, Carmen J.

AU - Li, Zhigang

AU - Karagas, Margaret R.

AU - Robbins, David J

PY - 2019/2/28

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N2 - 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 (p < 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.

AB - 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 (p < 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.

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