Maternal Levels of Endocrine Disrupting Chemicals in the First Trimester of Pregnancy Are Associated with Infant Cord Blood DNA Methylation

Details

• Personal Author:
  Dolinoy DC ; Domino SE ; Goodrich JM ; Meeker JD ; Montrose L ; Padmanabhan V ; Treadwell MC ; Watkins DJ
• Description:
  Endocrine disrupting chemicals (EDCs) pose a public health risk through disruption of normal biological processes. Identifying toxicoepigenetic mechanisms of developmental exposure-induced effects for EDCs, such as phthalates or bisphenol A (BPA), is essential. Here, we investigate whether maternal exposure to EDCs is predictive of infant DNA methylation at candidate gene regions. In the Michigan Mother-Infant Pairs (MMIP) cohort, DNA was extracted from cord blood leukocytes for methylation analysis by pyrosequencing (n = 116) and methylation changes related to first trimester levels of 9 phthalate metabolites and BPA. Growth and metabolism-related genes selected for methylation analysis included imprinted (IGF2, H19) and non-imprinted (PPARA, ESR1) genes along with LINE-1 repetitive elements. Findings revealed decreases in methylation of LINE-1, IGF2, and PPARA with increasing phthalate concentrations. For example, a log unit increase in SDEHP corresponded to a 1.03 [95% confidence interval (CI): -1.83, -0.22] percentage point decrease in PPARA methylation. Changes in DNA methylation were also inversely correlated with PPARA gene expression determined by RT-qPCR (r = -0.34, P = 0.02), thereby providing evidence in support of functional relevance. A sex-stratified analysis of EDCs and DNA methylation showed that some relationships were female-specific. For example, urinary BPA exposure was associated with a 1.35 (95%CI: -2.69, -0.01) percentage point decrease in IGF2 methylation and a 1.22 (95%CI: -2.27, -0.16) percentage point decrease in PPARA methylation in females only. These findings add to a body of evidence suggesting epigenetically labile regions may provide a conduit linking early exposures with disease risk later in life and that toxicoepigenetic susceptibility may be sex specific. [Description provided by NIOSH]
• Subjects:
  Cohort Studies Endocrine System Occupational Health Phthalic Acids Pregnancy Safety Sex Characteristics Toxicology Women
• Keywords:
  Author Keywords: Toxicoepigenetics Bisphenol A BPA Cohort Studies DNA Methylation DOHaD Endocrine Disruptors Metabolism Phthalate Phthalates Prenatal Exposure Sex Factors

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• ISSN:
  1559-2294
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Michigan ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  301-309
• Volume:
  13
• Issue:
  3
• NIOSHTIC Number:
  nn:20056612
• Citation:
  Epigenetics 2018 Mar; 13(3):301-309
• Contact Point Address:
  Vasantha Padmanabhan, Department of Environmental Health Sciences, 6150 SPH2, 1420 Washington Heights, Ann Arbor, MI 48109, USA
• Email:
  vasantha@umich.edu
• CAS Registry Number:
  2,2-Bis(4-hydroxyphenyl)propane (CAS RN 80-05-7)
• Federal Fiscal Year:
  2018
• Performing Organization:
  University of Michigan, Ann Arbor
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Epigenetics
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:385c31d7d0fbedbc08e0cfe495c5327f7d6c20a7990bd8005362e46fbd1e9952872c68916e27422832cb78fe083af306ed6fb66defb2eb1525af23e7b2c47bfd
• Download URL:
  https://stacks.cdc.gov/view/cdc/214185/cdc_214185_DS1.pdf
• File Type:
  [PDF - 869.88 KB ]