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

LINE-1 and <i>EPAS1</i> DNA methylation associations with high-altitude exposure

Recent discoveries indicate a genetic basis for high-altitude adaptation among human groups who have resided at high altitude for millennia, including Andeans, Tibetans, and Ethiopians. Yet, genetics alone does not explain the extent of variation in altitude-adaptive phenotypes. Current and past environments may also play a role, and one way to determine the effect of the environment is through the epigenome. To characterize if Andean adaptive responses to high altitude have an epigenetic component, we analyzed DNA methylation of the promoter region of EPAS1 and LINE-1 repetitive element among 572 Quechua individuals from high- (4,388 m) and low-altitude (0 m) in Peru. Participants recruited at high altitude had lower EPAS1 DNA methylation and higher LINE-1 methylation. Altitude of birth was associated with higher LINE-1 methylation, not with EPAS1 methylation. The number of years lived at high altitude was negatively associated with EPAS1 methylation and positively associated with LINE-1 methylation. We found four one-carbon metabolism SNPs (MTHFD1 rs2236225, TYMS rs502396, FOLH1 rs202676, GLDC rs10975681) that cumulatively explained 11.29% of the variation in average LINE-1 methylation. And identified an association between LINE-1 methylation and genome-wide SNP principal component 1 that distinguishes European from Indigenous American ancestry suggesting that European admixture decreases LINE-1 methylation. Our results indicate that both current and lifetime exposure to high-altitude hypoxia have an effect on EPAS1 and LINE-1 methylation among Andean Quechua, suggesting that epigenetic modifications may play a role in high-altitude adaptation.</p

MMIP Ox Stress Supplemental Tables Revision clean.docx

Supplemental data for the report submitted to Journal of Clinical Endocrinology and Metabolism titled "Maternal Exposure to Environmental Disruptors and Sexually-Dimorphic Changes in Maternal and Neonatal Oxidative Stress"<br

Data from: Maternal Exposure to Environmental Disruptors and Sexually-Dimorphic Changes in Maternal and Neonatal Oxidative Stress

Supplemental tables and figures from: Maternal Exposure to Environmental Disruptors and Sexually-Dimorphic Changes in Maternal and Neonatal Oxidative Stres

Per- and Polyfluoroalkyl Substances (PFAS), Epigenetic Age, and DNA Methylation: A Cross-Sectional Study of Firefighters

Supplemental Table S1. Serum PFAS Concentrations (geometric means, ng/mL) by Categorical Demographic Variables Supplemental Table S2. Significantly Differentially Methylated CpG Sites by PFAS Seum Concentration (at q-value Supplemental Table S3. Significantly Differentially Methylated Regions by PFAS Exposure Supplemental Table S4. Pathways Enriched for Differential Methylation by PFAS Exposure Supplemental Table S5. Association between Serum PFAS Concentrations (ln-transformed ng/mL) and Cell Type Estimates </div