Dataset Information

Trimester-Specific Associations of Prenatal Lead Exposure With Infant Cord Blood DNA Methylation at Birth.

ABSTRACT: Gestational exposure to lead (Pb) adversely impacts offspring health through multiple mechanisms, one of which is the alteration of the epigenome including DNA methylation. This study aims to identify differentially methylated CpG sites associated with trimester-specific maternal Pb exposure in umbilical cord blood (UCB) leukocytes. Eighty-nine mother-child dyads from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) longitudinal birth cohorts with available UCB samples were selected for DNA methylation analysis via the Infinium Methylation EPIC BeadChip, which quantifies methylation at >850?000 CpG sites. Maternal blood lead levels (BLLs) during each trimester (T1: 6.56?±?5.35?µg/dL; T2: 5.93?±?5.00?µg/dL; T3: 6.09?±?4.51?µg/dL), bone Pb (patella: 11.8?±?9.25?µg/g; tibia: 11.8?±?6.73?µg/g), a measure of cumulative Pb exposure, and UCB Pb (4.86?±?3.74?µg/dL) were measured. After quality control screening, data from 786?024 CpG sites were used to identify differentially methylated positions (DMPs) and differentially methylated regions (DMRs) by Pb biomarkers using separate linear regression models, controlling for sex and estimated UCB cell-type proportions. We identified 3 DMPs associated with maternal T1 BLL, 2 with T3 BLL, and 2 with tibia bone Pb. We identified one DMR within PDGFRL associated with T1 BLL, one located at chr6:30095136-30095295 with T3 BLL, and one within TRHR with tibia bone Pb (adjusted P-value?

SUBMITTER: Rygiel CA

PROVIDER: S-EPMC7372614 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Trimester-Specific Associations of Prenatal Lead Exposure With Infant Cord Blood DNA Methylation at Birth.

Rygiel Christine A CA Dolinoy Dana C DC Perng Wei W Jones Tamara R TR Solano Maritsa M Hu Howard H Téllez-Rojo Martha M MM Peterson Karen E KE Goodrich Jaclyn M JM

Epigenetics insights 20200720

Gestational exposure to lead (Pb) adversely impacts offspring health through multiple mechanisms, one of which is the alteration of the epigenome including DNA methylation. This study aims to identify differentially methylated CpG sites associated with trimester-specific maternal Pb exposure in umbilical cord blood (UCB) leukocytes. Eighty-nine mother-child dyads from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) longitudinal birth cohorts with available UCB samples were ...[more]

PMID: 32734142

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Project description:BackgroundMercury is a global pollutant, and prenatal exposure is associated with adverse health effects. To date, no studies have evaluated the association between prenatal mercury exposure and DNA hydroxymethylation, an epigenetic modification important for tissue differentiation and embryonic development.ObjectivesWe sought to evaluate the association between prenatal mercury exposure and offspring global DNA methylation and hydroxymethylation at birth and test for persistence of the association in childhood.MethodsWithin Project Viva, a U.S. prebirth cohort, we examined associations of maternal second trimester red blood cell mercury (RBC-Hg) concentrations with global 5-hydroxymethylcytosine (%-5hmC) and 5-methylcytosine (%-5mC) DNA content in blood collected at birth (n=306), early childhood (n=68; 2.9 to 4.9 y), and midchildhood (n=260; 6.7 to 10.5 y).ResultsMedian prenatal RBC-Hg concentration was 3.23?g/g [interquartile?range?(IQR)=3.29]. At birth, median cord blood %-5mC, %-5hmC, and their ratio were 4.95%, 0.22%, and 24.37, respectively. The mean adjusted difference [95% confidence interval (CI)] of blood %-5hmC for a doubling in prenatal RBC-Hg concentration was -0.013% (-0.029, 0.002), -0.031% (-0.056, -0.006), and 0.005% (-0.007, 0.018) at birth, early, and midchildhood, respectively. The corresponding relative adjusted change in the genomic ratio of %-5mC to %-5hmC for a doubling in prenatal RBC-Hg concentration was 4.70% (0.04, 9.58), 22.42% (7.73, 39.11), and 0.73% (-4.18, 5.88) at birth, early, and midchildhood, respectively. No associations were present between prenatal maternal RBC-Hg and %-5mC at any time point.ConclusionsPrenatal mercury exposure was associated with lower %-5hmC genomic content and a corresponding increase in the ratio of %-5mC to %-5hmC in cord blood. This association was persistent in early but not midchildhood blood. Our results demonstrate the potential malleability of epigenetic modifications associated with mercury exposure in utero. https://doi.org/10.1289/EHP1467.

Project description:BACKGROUND:Bisphenol A (BPA) is an endocrine disruptor that affects fetal growth in experimental studies. Bisphenol F (BPF) and bisphenol S (BPS), which have been substituted for BPA in some consumer products, have also shown endocrine-disrupting effects in experimental models. However, the effects of BPF and BPS on fetal growth in humans are unknown. OBJECTIVES:Our goal was to investigate trimester-specific associations of urinary concentrations of BPA, BPF, and BPS with size at birth. METHODS:The present study included 845 pregnant women from Wuhan, China (2013-2015), who provided one urine sample in each of the first, second, and third trimesters. Linear regressions with generalized estimating equations were applied to estimate trimester-specific associations of urinary bisphenol concentrations with birth weight, birth length, and ponderal index. Linear mixed-effects models were used to identify potential critical windows of susceptibility to bisphenols by comparing the exposure patterns of newborns in the 10th percentile of each birth anthropometric measurement to that of those in the 90th percentile. RESULTS:Medians (25th-75th percentiles) of urinary concentrations of BPA, BPF, and BPS were 1.40 (0.19-3.85), 0.65 (0.34-1.39), and 0.38 (0.13-1.11) ng/mL, respectively. Urinary BPA concentrations in different trimesters were inversely, but not significantly, associated with birth weight and ponderal index. Urinary concentrations of BPF and BPS during some trimesters were associated with significantly lower birth weight, birth length, or ponderal index, with significant trend p-values (ptrend<0.05) across quartiles of BPF and BPS concentrations. The observed associations were unchanged after additionally adjusting for other bisphenols. In addition, newborns in the 10th percentile of each birth anthropometry measure had higher BPF and BPS exposures during pregnancy than newborns in the 90th percentile of each outcome. CONCLUSIONS:Prenatal exposure to BPF and BPS was inversely associated with size at birth in this cohort. Replication in other populations is needed. https://doi.org/10.1289/EHP4664.

Project description:BackgroundGestational lead (Pb) exposure can adversely affect offspring health through multiple mechanisms, including epigenomic alterations via DNA methylation (5mC) and hydroxymethylation (5hmC), an intermediate in oxidative demethylation. Most current methods do not distinguish between 5mC and 5hmC, limiting insights into their individual roles.ObjectiveOur study sought to identify the association of trimester-specific (T1, T2, T3) prenatal Pb exposure with 5mC and 5hmC levels at multiple cytosine-phosphate-guanine sites within gene regions previously associated with prenatal Pb (HCN2, NINJ2, RAB5A, TPPP) in whole blood leukocytes of children ages 11-18 years of age.MethodsParticipants from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohorts were selected (n=144) for pyrosequencing analysis following oxidative or standard sodium bisulfite treatment. This workflow directly quantifies total methylation (5mC+5hmC) and 5mC only; 5hmC is estimated by subtraction.ResultsParticipants were 51% male, and mean maternal blood lead levels (BLL) were 6.43±5.16μg/dL in Trimester 1 (T1), 5.66±5.21μg/dL in Trimester 2 (T2), and 5.86±4.34μg/dL in Trimester 3 (T3). In addition, 5hmC levels were calculated for HCN2 (mean±standard deviation(SD), 2.08±4.18%), NINJ2 (G/C: 2.01±5.95; GG: 0.90±3.97), RAB5A (0.66±0.80%), and TPPP (1.11±6.67%). Furthermore, 5mC levels were measured in HCN2 (81.3±9.63%), NINJ2 (heterozygotes: 38.6±7.39%; GG homozygotes: 67.3±9.83%), RAB5A (1.41±1.21%), and TPPP (92.5±8.03%). Several significant associations between BLLs and 5mC/5hmC were identified: T1 BLLs with 5mC in HCN2 (β=-0.37, p=0.03) and 5hmC in NINJ2 (β=0.49, p=0.003); T2 BLLs with 5mC in HCN2 (β=0.37, p=0.03) and 5hmC in NINJ2 (β=0.27, p=0.008); and T3 BLLs with 5mC in HCN2 (β=0.50, p=0.01) and NINJ2 (β=-0.35, p=0.004) and 5hmC in NINJ2 (β=0.45, p<0.001). NINJ2 5mC was negatively correlated with gene expression (Pearson r=-0.5, p-value=0.005), whereas 5hmC was positively correlated (r=0.4, p-value=0.04).DiscussionThese findings suggest there is variable 5hmC in human whole blood and that prenatal Pb exposure is associated with gene-specific 5mC and 5hmC levels at adolescence, providing evidence to consider 5hmC as a regulatory mechanism that is responsive to environmental exposures. https://doi.org/10.1289/EHP8507.

Dataset Information

Trimester-Specific Associations of Prenatal Lead Exposure With Infant Cord Blood DNA Methylation at Birth.

Publications

Trimester-Specific Associations of Prenatal Lead Exposure With Infant Cord Blood DNA Methylation at Birth.

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