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Multigenerational epigenetic inheritance in humans: DNA methylation changes associated with maternal exposure to lead can be transmitted to the grandchildren - PubMed

  • ️Thu Jan 01 2015

Multigenerational epigenetic inheritance in humans: DNA methylation changes associated with maternal exposure to lead can be transmitted to the grandchildren

Arko Sen et al. Sci Rep. 2015.

Abstract

We report that the DNA methylation profile of a child's neonatal whole blood can be significantly influenced by his or her mother's neonatal blood lead levels (BLL). We recruited 35 mother-infant pairs in Detroit and measured the whole blood lead (Pb) levels and DNA methylation levels at over 450,000 loci from current blood and neonatal blood from both the mother and the child. We found that mothers with high neonatal BLL correlate with altered DNA methylation at 564 loci in their children's neonatal blood. Our results suggest that Pb exposure during pregnancy affects the DNA methylation status of the fetal germ cells, which leads to altered DNA methylation in grandchildren's neonatal dried blood spots. This is the first demonstration that an environmental exposure in pregnant mothers can have an epigenetic effect on the DNA methylation pattern in the grandchildren.

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Figure 1
Figure 1. Maternal prenatal exposure to lead (Pb) and its effect on the child’s neonatal and current blood.

(A) Illustration depicting the plan of study. The F1 represents the maternal grandmother, F2 the mother in this study when she was a fetus, and F3 the child born when the mother matured. (B) A-clustering followed by differential methylation analysis by generalized estimating equation (GEE) revealed 115 CpG clusters mapping to 346 CpG sites differentially methylated in child’s neonatal blood spots (CNBS) with high BLL in mother’s neonatal blood spot (MNBS) compared to CNBS with low BLL in MNBS. We observed more hyper-methylated CpG clusters (n = 98) compared to hypo-methylated CpG clusters (n = 17) at an exposure effect cut-off of 0.05 (5%) and an FDR p-value ≤ 0.05. (C) Differential methylation analysis revealed no association between DNA methylation levels in a child’s current blood spot (CCBS) and mother’s neonatal BLL (n = 14). (D) Overlap between the 320 CpG sites mapping to 116 clusters identified in a previous study, and the 564 CpG sites mapping to 183 clusters identified in this study. The 320 CpG sites (CCBS postnatal) correspond to the effects of BLL in CNBS on CCBS DNA methylation that we reported earlier. The 564 CpG sites (CNBS prenatal) correspond to the effects of BLL in MNBS on CNBS DNA methylation that we report in this study (Fig. 1B). Note children recruited for the previous study are the same as in this study.

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References

    1. Wright R. O. et al. Biomarkers of lead exposure and DNA methylation within retrotransposons. Environ Health Perspect 118, 790–795, 10.1289/ehp.0901429 (2010). - DOI - PMC - PubMed
    1. Dosunmu R., Alashwal H. & Zawia N. H. Genome-wide expression and methylation profiling in the aged rodent brain due to early-life Pb exposure and its relevance to aging. Mech Ageing Dev 133, 435–443, 10.1016/j.mad.2012.05.003 (2012). - DOI - PMC - PubMed
    1. Sen A. et al. Early life lead exposure causes gender specific changes in the DNA methylation profile of DNA extracted from dried blood spots. Epigenomics in press, 10.2217/EPI.15.2 (2015). - DOI - PMC - PubMed
    1. Senut M. C. et al. Lead exposure disrupts global DNA methylation in human embryonic stem cells and alters their neuronal differentiation. Toxicol Sci 139, 142–161, 10.1093/toxsci/kfu028 (2014). - DOI - PMC - PubMed
    1. Wolff G. L., Kodell R. L., Moore S. R. & Cooney C. A. Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice. FASEB journal: official publication of the Federation of American Societies for Experimental Biology 12, 949–957 (1998). - PubMed

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