Cardenas Andres, Rifas-Shiman Sheryl L, Godderis Lode, Duca Radu-Corneliu, Navas-Acien Ana, Litonjua Augusto A, DeMeo Dawn L, Brennan Kasey J, Amarasiriwardena Chitra J, Hivert Marie-France, Gillman Matthew W, Oken Emily, Baccarelli Andrea A
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute , Boston, Massachusetts, USA.
Department of Public Health and Primary Care, Katholieke Universiteit Leuven , Leuven, Belgium.
Environ Health Perspect. 2017 Aug 29;125(8):087022. doi: 10.1289/EHP1467.
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.
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.
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 (=306), early childhood (=68; 2.9 to 4.9 y), and midchildhood (=260; 6.7 to 10.5 y).
Median prenatal RBC-Hg concentration was 3.23μg/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.
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 . https://doi.org/10.1289/EHP1467.
汞是一种全球污染物，孕期接触汞与不良健康影响相关。迄今为止，尚无研究评估孕期汞暴露与DNA羟甲基化之间的关联，而DNA羟甲基化是一种对组织分化和胚胎发育很重要的表观遗传修饰。
我们试图评估孕期汞暴露与出生时后代全基因组DNA甲基化和羟甲基化之间的关联，并检测这种关联在儿童期是否持续存在。
在“活力计划”（美国一个产前队列研究）中，我们研究了孕中期母体红细胞汞（RBC-Hg）浓度与出生时（n = 306）、幼儿期（n = 68；2.9至4.9岁）和童年中期（n = 260；6.7至10.5岁）采集的血液中全基因组5-羟甲基胞嘧啶（%-5hmC）和5-甲基胞嘧啶（%-5mC）DNA含量之间的关联。
孕期RBC-Hg浓度中位数为3.23μg/g[四分位间距（IQR）= 3.29]。出生时，脐血%-5mC、%-5hmC及其比值的中位数分别为4.95%、0.22%和24.37。孕期RBC-Hg浓度翻倍时，出生时、幼儿期和童年中期血液中%-5hmC的平均校正差异[95%置信区间（CI）]分别为-0.013%（-0.029，0.002）、-0.031%（-0.056，-0.006）和0.005%（-0.007，0.018）。孕期RBC-Hg浓度翻倍时，出生时、幼儿期和童年中期%-5mC与%-5hmC基因组比值的相应相对校正变化分别为4.70%（0.04，9.58）、22.42%（7.73，39.11）和0.73%（-4.18，5.88）。在任何时间点，孕期母体RBC-Hg与%-5mC之间均无关联。
孕期汞暴露与脐血中较低的%-5hmC基因组含量以及%-5mC与%-5hmC比值相应增加有关。这种关联在幼儿期血液中持续存在，但在童年中期血液中不存在。我们的结果表明与汞暴露相关的表观遗传修饰具有潜在的可塑性。https://doi.org/10.1289/EHP1467
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