Inorganic Arsenic as an Endocrine Disruptor: Modulation of the Glucocorticoid Receptor Pathway in Placental Cells via CpG Methylation

Details

• Personal Author:
  Fry RC ; Martin EM ; Meakin CJ ; Nylander-French LA ; Szilagyi JT
• Description:
  Prenatal exposure to inorganic arsenic (iAs) has been associated with adverse developmental and reproductive outcomes. These outcomes may be tied to altered functionality of nuclear transcription factors such as the glucocorticoid receptor (GR) in the placenta and associated gene expression. The GR pathway is integral for proper fetal and placental development, and perturbations in this pathway may underlie observed associations between prenatal iAs exposure and adverse birth outcomes. We therefore set out to investigate whether iAs modulates the GR signaling pathway in placental cells. JEG-3 trophoblasts were exposed to environmentally-relevant doses of iAs, and mRNA expression assessed. To examine the links between iAs exposure, the GR signaling pathway, and epigenetic modification, DNA methylation levels were also quantified. Treatment with iAs altered the expression of 12 GR-genes that play a role in fetal and placental development. Furthermore, at a gene-specific level, mRNA abundance was associated with changes in DNA methylation patterning in JEG-3 cells, suggesting that the effects of iAs are mediated by epigenetic mechanisms. The identified target genes have been associated with prenatal iAs exposure, placental physiology, and fetal development. This study provides further evidence for iAs as an endocrine disruptor and provides insight as to the mechanisms by which prenatal iAs exposure may induce adverse birth outcomes. [Description provided by NIOSH]
• Subjects:
  Arsenic Endocrine System Fetus Inorganic Chemicals Occupational Health Pregnancy Safety Urogenital System
• Keywords:
  Cell Signaling Endocrine Disruptors Gene Expression Prenatal Exposure Reproductive Effects
• ISSN:
  0893-228X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  North Carolina ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  493-499
• Volume:
  32
• Issue:
  3
• NIOSHTIC Number:
  nn:20058296
• Citation:
  Chem Res Toxicol 2019 Mar; 32(3):493-499
• Contact Point Address:
  Rebecca C. Fry, Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina 27516, United States
• Email:
  rfry@unc.edu
• CAS Registry Number:
  Arsenic (CAS RN 7440-38-2)
• Federal Fiscal Year:
  2019
• Performing Organization:
  University of North Carolina, Chapel Hill
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Chemical Research in Toxicology
• End Date:
  20270630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e0c4792a5d80eb8de560c52358c3d282866702d9d2db61d27b56a293d2f42088edcb5d02afd9448228addf8b71871e637e95fbfc71660b2b5afcd404dcca6b87
• Download URL:
  https://stacks.cdc.gov/view/cdc/221423/cdc_221423_DS1.pdf
• File Type:
  [PDF - 1.10 MB ]