Maternal levels of endocrine disrupting chemicals in the first trimester of pregnancy are associated with infant cord blood DNA methylation

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.

Early pregnancy exposure to endocrine disrupting chemical mixtures are associated with inflammatory changes in maternal and neonatal circulation

“…As of October 2018, 289 women in the MMIP cohort have delivered. Other studies involving subsets of MMIP participants have been published previously 21,52,53 .…”

“…Details on phthalate and phenol exposure assessment have been previously published by Montrose et al ., 2018 53 . Briefly, using maternal urine samples collected between 8 and 14 weeks’ gestation, 12 phthalate metabolites and 12 phenol metabolites were quantified via isotope dilution liquid chromatography and tandem mass spectrometry.…”

Oestrogenic Endocrine Disruptors in the Placenta and the Fetus

“…Maternal exposure to BPA in early pregnancy predicts DNA methylation in newborns, which is associated with gene expression levels related to growth and metabolism. And DNA methylation has a potential impact on disease susceptibility in the fetus [54]. Female mice exposure to BPA during early pregnancy can result in impaired remodeling of uterine SAs, which has a negative effect on vasoconstrictive ability and blood flow velocity, limiting the blood supply to the placenta and fetus.…”

Fetal–Maternal Exposure to Endocrine Disruptors: Correlation with Diet Intake and Pregnancy Outcomes

“…A recent cohort study reported the negative association among first-trimester maternal exposure to BPA and phthalates and term cord blood methylation of imprinted (H19, IGF2) and non-imprinted (PPARA, ESR1) genes and LINE-1 repetitive elements [ 82 ], epigenetic targets associated with growth, development and metabolism. Of note, a sex-stratified analysis for DNA methylation revealed that these EDC-induced effects were female-specific [ 82 ], confirming the epigenetics-related sexually dimorphic effects of EDC exposure during prenatal development previously demonstrated in several animal models [ 83 ]. A similar designed study was performed on 296 newborns from the CHAMACOS Mexican–American longitudinal birth cohort.…”