Gene Expression Throughout Life Affected By Early Lead Exposure

A link has been found between lead exposure in children and epigenetic changes in genes that are critical in growth regulation and brain development.

The team of researchers, led by North Carolina State University biologists Cathrine Hoyo and Randy Jirtle, found the alterations appear to persist into adulthood, with more effect in males. The study clarifies the long-term effects of early lead exposure on DNA, and could help develop therapies for treating or reversing the damage.

Hoyo commented:

“We now have the first human evidence for an association between early lead exposure and three aberrantly methylated regulatory regions of imprinted genes. But from a public health perspective, the results are very exciting because we can begin to think about identifying potential biological markers for early exposure to lead and other toxins in the environment.”

Along with colleagues Kim Dietrich of the University of Cincinnati, Yue Li of Duke University, and NC State’s David Skaar, the team spent several years focusing on regulatory regions within DNA that may link early lead exposure to specific diseases, characterizing 22 of these regions to date.

Researchers investigated the 22 regions to see if lead exposure affected DNA methylation, the process controlling how a gene is expressed, determining whether or not it is switched on or off. Where methylation is altered, genes are either turned off, or they are more active than they normally would be.

“Genes are like computers with both hardware and software,” says Jirtle. “Most scientists have been studying the hardware, which is the genetic sequence, without looking at the software, which is the regulatory layer that alters how that gene is expressed. This study gives us a first look at how the software may be affected by early exposure to lead.”

The team pinpointed three imprinted genes whose expression was affected in adulthood by lead exposure from birth to 6 and a half years of age:

  • PEG3 (methylation decreased)
  • IGF2/H19 (methylation decreased)
  • PLAGL1/HYMAI (methylation increased)

The methylation was gender-specific: decreased methylation for PEG3, which is associated with fetal development, affected males more than females, while the opposite was true for IGF2/H19. PLAGL1/HYMAI methylation, which increased, was not sex-specific.

Furthermore, they found that raised blood levels of lead later in postnatal development did not appear to have any other effects on the regulatory regions. Methylation alterations occurred during the first 12 months, even as lead exposure continued to increase over the study period.

Lead Exposure during Early Human Development and DNA Methylation of Imprinted Gene Regulatory Elements in Adulthood.
Cathrine Hoyo, et al
Environ Health Perspect; DOI: 10.1289/ehp.1408577

Image: Interaction of DNA (in orange) with histones (in blue). By Thomas Splettstoesser CC BY-SA 3.0