Lead from mom's bones influences baby's gene patterns.

Apr 21, 2009

Pilsner JR, H Hu, A Ettinger, BN Sanchez, RO Wright, D Cantonwine, A Lazarus, H Lamadrid-Figueroa, A Mercado-Garcia, MM Tellez-Rojo and M Hernandez-Avila. Influence of prenatal lead exposure on genomic methylation of cord blood DNA. Environmental Health Perspectives doi: 10.1289/ehp.0800497.




2009-0418pregnantprofile
mahalie, Flickr.

 

Lead released from a woman's bones during pregnancy can affect her developing baby's DNA in ways that can alter gene expression and possibly increase the child's lifelong susceptibility to disease. This is the first study to show that lead can influence genetic programming in human cells, and hence, gene expression, throughout life.

 

 

Context

The idea that exposures before birth can change development and have lifelong health effects is called fetal origins of disease. Original research linked poor nutrition to a host of adult health problems including heart disease and diabetes. More recently, animal studies show similar links with prebirth exposures to environmental toxins.

Preterm deliveries and low birth weight are associated with prebirth lead exposure. These are also risk factors for other health issues as the child grows into adulthood.

As a neurotoxin, lead can permanently affect brain development, altering intelligence, cognition and behavior. Lead exposure is associated with mental decline in old age and may be related to the risk of developing Alzheimer disease.

The epigenome is the genetic code that is read and translated into directions that control most development and body functions through life. Environmental exposures can permanently change the way these genes turn on and off, a process called 'gene expression.' The "epigenetic" changes are caused by reprogramming not by changes in the DNA sequence.

Methylation of DNA is one of the most studied epigentic processes. Methylation describes a process used by genes to control which genes are turned on and which genes are turned off. If the gene is turned off by methylation, then the activities that gene codes for won't be carried out.

Animal studies with monkeys and rodents find that lead exposure in early life affects epigenetic control of genes. In those studies, lead changed the genes that control expression and regulation of proteins and enzymes associated with Alzheimer's disease (Basha et al. 2005; Wu et al. 2008)

Lead is a natural metal used in a number of manufacturing operations. It is released into the environment during mining, smelting, steel welding, lead soldering, battery manufacturing and from firing ranges and auto repair shops.

Consumer products can also contain lead. Jewelry, toys, keys and some folk medicines are examples. Government agencies regulate the amount of lead in products. Some items are recalled due to the lead. 

People are exposed to lead through air, dust, water, food and soil. In older buildings, lead paint and dust are major sources, especially for children, who ingest the metal through hand-to-mouth activity and by mouthing toys.

Like calcium and other minerals, lead is deposited and stored in bones, where, over time, it slowly leaves the skeleton. Pregnancy increases that rate of transfer exposing mother and developing child to current and previously stored sources of lead.

What did they do?

This study is part of the larger Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study, which is designed to examine how a mother's total lead burden affects fetal and infant development.

Between 1994 and 1995, Pilsner and colleagues recruited pregnant women from three hospitals in Mexico City. Lead levels were measured in two ways—in umbilical cord blood samples collected at birth and in the mother's leg bones (left tibia and left patella) about one month after they had their babies. 

The lead levels were compared to changes in methylation of two important genes, LINE-1 and Alu, that regulate expression. DNA methylation was measured in 103 umbilical cord blood samples.

During the statistical analysis, researchers took into account factors such as maternal age at delivery, maternal education, cigarette smoking during pregnancy and infant gender.


What did they find?

The most significant findings were related to the impact of maternal cumulative bone lead measures on genomic DNA methylation.

The mothers' tibia and patella lead measures were found to be inversely associated with methylation levels of the two genes (Alu and LINE-1). That is, as lead levels increased in the bones, gene methylation decreased in the blood cells sampled from the umbilical cord blood.

Both Alu and LINE-1 "are known to be heavily methylated in normal tissue," according to the authors.

No associations were found between cord blood lead levels -- which would indicate current lead exposures -- and DNA methylation.

For the first time, researchers find that prenatal exposure to lead stored in a mother's bones can influence the way genes are programmed and expressed later in life. The results are in line with prior studies on animals that also find that lead can affect and change epigenetic programming.

These changes to when and how DNA is read and translated can have permanent and lifelong impacts on susceptibility to disease. This study may give us clues as to how fetal chemical exposure can predispose us to disease much later in life.

Specifically, the results are important because they increase understanding of how exposure may cause the known impacts of lead on health. The change to epigenetic programming "may be a mechanism by which lead alters susceptibility to diseases such as Alzheimer’s disease," the authors report.

Based on the findings, lead exposure may influence many generations, even after the exposure has stopped. A mother and developing child will be exposed to both current lead sources and lead that had been previously stored in the mother’s bones. Lead that is transferred from mother to child, and maybe grandchild and beyond, could alter how the DNA that guides all body functions is expressed in subsequent generations.

The authors caution for potential limitations of the study. First, the blood cells -- called leukocytes -- used in this study may not represent DNA methylation changes in other tissue, such as the central nervous system. Also, the blood cell DNA used in the study is a mix of numerous cell types, which may have influenced the findings.

Additional research is necessary to confirm these findings and investigate whether prenatal lead exposure influences epigenome-wide and gene-specific DNA methylation.

Resources

Basha, MR, W Wei, SA Bakheet, N Benitez, HK Siddiqi YW Ge et al. 2005. The fetal basis of
amyloidogenesis: exposure to lead and latent overexpression of amyloid precursor protein and
beta-amyloid in the aging brain
. Journal of Nueroscience 25(4):823-829.

Bradbury, J. Human Epigenome Project—up and running. PLoS Biology 1(3): e82.

Jedrychowski, W, F{ Perera, J Jankowski, D Mrozek-Budzyn, E Mroz, E Flak, S Edwards, A Skarupa and I Lisowska-Miszczyk. 2009. Very low prenatal exposure to lead and mental development of children in infancy and early childhood. Krakow Prospective
Cohort Study
. Neuroepidemiology 32: 270-278.

LaFee, S. 2009. Bioscientists focus on the new, vast potential of epigenetics. The San Diego Union-Tribune March 30.

 Lead. Agency for Toxic Substances and Diseasae Registry

What is epigenetics? The European Epigenome Network of Excellence. 

Wu J, MR Basha, B Brock, DP Cox, F Cardozo-Pelaez, CA McPherson, et al. 2008. Alzheimer's disease (AD)-like pathology in aged monkeys after infantile exposure to environmental metal lead (Pb): evidence for a developmental origin and environmental link for AD. Journal of Neuroscience 28(1):3-9.

 

 

Lead & children's health
More news about
Lead & children's health