Douglas Ruden, Ph.D.
Wayne State University
NIEHS Grants R01ES012933, R21ES021893, P30ES020957
An NIEHS-funded study showed that mothers with high neonatal blood levels of lead — indicating that the mothers themselves experienced lead exposure in the womb — can bring about epigenetic changes in their unborn children. This study is one of the first to show that an environmental exposure in pregnant mothers can have an epigenetic effect on DNA methylation in their grandchildren.
Epigenetic changes, such as DNA methylation, are chemical modifications that change how DNA is expressed without altering the genetic code. For the study, the researchers measured lead levels and methylation at over 450,000 DNA locations, or loci, from current blood and neonatal dried blood spots from both the mother and child of 35 mother-infant pairs. The samples came from the Michigan Neonatal Biobank, which contains most of the neonatal dried blood spots from children born in Michigan since 1984.
The researchers found that mothers whose own neonatal blood spots showed high lead levels, correlated with DNA methylation changes at 564 loci in their children’s neonatal blood. These results suggest that lead 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. The study also showed that the altered DNA methylation status detected in the grandchildren’s blood is apparently normalized during postnatal development.
Citation: Sen A, Heredia N, Senut MC, Land S, Hollocher K, Lu X, Dereski MO, Ruden DM. 2015. Multigenerational epigenetic inheritance in humans: DNA methylation changes associated with maternal exposure to lead can be transmitted to the grandchildren. Sci Rep 5:14466.