TY - JOUR
T1 - Prenatal exposure to mercury
T2 - Associations with global DNA methylation and hydroxymethylation in cord blood and in childhood
AU - Cardenas, Andres
AU - Rifas-Shiman, Sheryl L.
AU - Godderis, Lode
AU - Duca, Radu Corneliu
AU - Navas-Acien, Ana
AU - Litonjua, Augusto A.
AU - Demeo, Dawn L.
AU - Brennan, Kasey J.
AU - Amarasiriwardena, Chitra J.
AU - Hivert, Marie France
AU - Gillman, Matthew W.
AU - Oken, Emily
AU - Baccarelli, Andrea A.
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health (R01 NR013945, R01 ES021357, R01 HD034568, K24 HD069408, R01 ES016314, R01 HL 111108, and P30 ES009089).
Publisher Copyright:
© 2017, Public Health Services, US Dept of Health and Human Services. All rights reserved.
PY - 2017/8
Y1 - 2017/8
N2 - Background: Mercury 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. Objectives: We 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. Methods: Within 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). Results: Median prenatal RBC-Hg concentration was 3.23 μg/g [interquartilerange (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. Conclusions: Prenatal 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.
AB - Background: Mercury 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. Objectives: We 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. Methods: Within 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). Results: Median prenatal RBC-Hg concentration was 3.23 μg/g [interquartilerange (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. Conclusions: Prenatal 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.
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U2 - 10.1289/EHP1467
DO - 10.1289/EHP1467
M3 - Article
C2 - 28934725
AN - SCOPUS:85031751411
SN - 0091-6765
VL - 125
JO - Environmental health perspectives
JF - Environmental health perspectives
IS - 8
ER -