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.
Highlights
Studies have suggested that exposure to heavy metal toxicants can influence the global DNA methylation profile
We found that acute childhood Pb exposure can alter the methylation profile of DNA isolated from the blood[3]
Approximately 1 μ g of DNA was isolated from each dried bloodspot and DNA methylation levels at over 450,000 CpG sites were determined with the Illumina Human Methylation 450 K (HM450K) assay
Summary
Studies have suggested that exposure to heavy metal toxicants can influence the global DNA methylation profile. In recent studies conducted in our lab we have demonstrated that Pb-exposure can cause locus specific changes in DNA methylation which can be detected in dried blood spots (DBS)[3] and in human embryonic stem cells (hESCs)[4]. We tested the hypothesis that human-fetal-germ-cell exposure to environmental toxins causes epigenetic changes in the newborn blood from a grandchild of an exposed pregnant woman (Fig. 1A). In the later developmental stages, the DNA methylation pattern is maintained by the maintenance DNA methyltransferase (DNMT1)[12] This may contribute to transmission of epigenetic traits from the mother to her grandchildren. We assume that the locus specific DNA methylation changes due to Pb exposure in the mother was carried over to her grandchildren because she exposed her fetal germ cells during the implantation stage of her pregnancy
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