期刊
REPRODUCTIVE TOXICOLOGY
卷 57, 期 -, 页码 43-49出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.reprotox.2015.05.002
关键词
Epigenetics; In utero; Methylation; Manganese; Placenta; Pregnancy; LOC284276
资金
- NIH-NIMH [R01MH094609]
- US EPA [RD83544201]
- NHLBI [T32HL076134-04]
- National Institutes of Health [P50-DA-036107-01]
- NIH-NIEHS [R01 ES022223, P01 ES022832, T32ES007272]
Adequate micronutrient intake, including manganese (Mn), is important for fetal development. Both Mn deficiencies and excess exposures are associated with later-life disease, and Mn accumulates in the placenta. Placental functional alterations may alter fetal programming and lifelong health, and we hypothesized that prenatal exposures to Mn may alter placental function through epigenetic mechanisms. Using Illumina's HumanMethylation450 BeadArray, DNA methylation of >485,000 CpG loci genome-wide was interrogated in 61 placental samples and Mn associations assessed genome-wide via omnibus test (p = 0.045). 713 loci were associated with Mn exposure (p<0.0001). Five significantly differentially-methylated (p < 1.3 x 10(-7)) loci reside in neurodevelopmental, fetal growth and cancer-related genes. cg22284422, within the uncharacterized LOC284276 gene, was associated with birth weight; for every 10% increase in methylation, lower birth weights were observed, with an average decrease of 293.44g. Our observations suggest a link between prenatal micronutrient levels, placental epigenetic status and birth weight, although these preliminary results require validation. (C) 2015 Elsevier Inc. All rights reserved.
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