Title: Maternal levels of endocrine disrupting chemicals in the first trimester of pregnancy are associated with infant cord blood DNA methylation.
Authors: Montrose, Luke; Padmanabhan, Vasantha; Goodrich, Jaclyn M; Domino, Steven E; Treadwell, Marjorie C; Meeker, John D; Watkins, Deborah J; Dolinoy, Dana C
Published In Epigenetics, (2018)
Abstract: 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 ΣDEHP 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.
PubMed ID: 29513082
MeSH Terms: Benzhydryl Compounds/urine; DNA Methylation/drug effects; DNA Methylation/genetics*; Endocrine Disruptors/blood*; Endocrine Disruptors/toxicity; Endocrine Disruptors/urine; Environmental Pollutants/toxicity; Estrogen Receptor alpha/genetics; Female; Fetal Blood/drug effects*; Gene Expression Regulation, Developmental/drug effects; Genomic Imprinting/drug effects*; Humans; Infant; Insulin-Like Growth Factor II/genetics; Long Interspersed Nucleotide Elements/genetics; Male; PPAR alpha/genetics; Phenols/urine; Pregnancy; Pregnancy Trimester, First; RNA, Long Noncoding/genetics