Montrose, Luke Padmanabhan, Vasantha Goodrich, Jaclyn M. Domino, Steven E. Treadwell, Marjorie C. Meeker, John D. Watkins, Deborah J. Dolinoy, Dana C. Maternal levels of endocrine disrupting chemicals in the first trimester of pregnancy are associated with infant cord blood DNA methylation <p>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 (<i>IGF2</i>, <i>H19</i>) and non-imprinted (<i>PPARA</i>, <i>ESR1</i>) genes along with LINE-1 repetitive elements. Findings revealed decreases in methylation of LINE-1, <i>IGF2</i>, and <i>PPARA</i> 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 <i>PPARA</i> methylation. Changes in DNA methylation were also inversely correlated with <i>PPARA</i> gene expression determined by RT-qPCR (r = −0.34, <i>P</i> = 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 <i>IGF2</i> methylation and a 1.22 (95%CI: −2.27, −0.16) percentage point decrease in <i>PPARA</i> 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.</p> Toxicoepigenetics;DOHaD;DNA methylation;metabolism;phthalate;BPA 2019-08-15
    https://tandf.figshare.com/articles/dataset/Maternal_levels_of_endocrine_disrupting_chemicals_in_the_first_trimester_of_pregnancy_are_associated_with_infant_cord_blood_DNA_methylation/6154457
10.6084/m9.figshare.6154457.v2