Cited by 276Heavy Metal Exposure and ToxicityEpigenetics and DNA MethylationBirth, Development, and Health

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Influence of Prenatal Lead Exposure on Genomic Methylation of Cord Blood DNA

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Pilsner, J. Richard, Hu, Howard, Ettinger, Adrienne, Sánchez, Brisa N., Wright, Robert O., Cantonwine, David, Lazarus, Alicia, Lamadrid-Figueroa, Héctor, Mercado-García, Adriana, Téllez-Rojo, Martha Maria, Hernández-Avila, Mauricio·2009·Environmental Health Perspectives

DOI 10.1289/ehp.0800497PMC PMC2737027

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Abstract

Background: Fetal lead exposure is associated with adverse pregnancy outcomes and developmental and cognitive deficits; however, the mechanism(s) by which lead-induced toxicity occurs remains unknown. Epigenetic fetal programming via DNA methylation may provide a pathway by which environmental lead exposure can influence disease susceptibility. Objective: This study was designed to determine whether prenatal lead exposure is associated with alterations in genomic methylation of leukocyte DNA levels from umbilical cord samples. Methods: We measured genomic DNA methylation, as assessed by Alu and LINE-1 (long interspersed nuclear element-1) methylation via pyrosequencing, on 103 umbilical cord blood samples from the biorepository of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study group. Prenatal lead exposure had been assessed by measuring maternal bone lead levels at the mid-tibial shaft and the patella using a spot-source 109Cd K-shell X-ray fluorescence instrument. Results: We found an inverse dose–response relationship in which quartiles of patella lead correlated with cord LINE-1 methylation (p for trend = 0.01) and and tibia lead correlated with Alu methylation (p for trend = 0.05). In mixed effects regression models, maternal tibia lead was negatively associated with umbilical cord genomic DNA methylation of Alu (β= −0.027; p = 0.01). We found no associations between cord blood lead and cord genomic DNA methylation. Conclusions: Prenatal lead exposure is inversely associated with genomic DNA methylation in cord blood. These data suggest that the epigenome of the developing fetus can be influenced by maternal cumulative lead burden, which may influence long-term epigenetic programming and disease susceptibility throughout the life course.

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Authors: Pilsner, J. R., Hu, H., Ettinger, A., Sánchez, B. N., Wright, R. O., Cantonwine, D., Lazarus, A., Lamadrid-Figueroa, H., Mercado-García, A., Téllez-Rojo, M. M., & Hernández-Avila, M.
Affiliations: University of Michigan (US)
Brigham and Women's Hospital (US)
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
Division of Program Evaluation and Biostatistics, Center for Evaluation Research and Surveys, National Institute of Public Health, Cuernavaca, Morelos, Mexico
Division of Environmental Health, Center for Population Health Research, National Institute of Public Health, Mexico City, Mexico
Ministry of Health, Mexico City, Mexico
Corresponding author: Pilsner, J. Richard
ORCID: Pilsner, J. Richard
Hu, Howard
Ettinger, Adrienne
Sánchez, Brisa N.
Wright, Robert O.
Cantonwine, David
Venue: Environmental Health Perspectives
Publisher: American Chemical Society (ACS)
Published: 2009-03-25
Volume: 117
Issue: 9
Pages: 1466-1471
ISSN: 0091-6765 (ISSN-L)
1552-9924
DOI: 10.1289/ehp.0800497
PMC: PMC2737027
OpenAlex: W2088501324
Cited by: 275
References: 53
Citations by year: 2026: 5 · 2025: 7 · 2024: 5 · 2023: 12 · 2022: 15 · 2021: 18 · 2020: 14 · 2019: 22 · 2018: 18 · 2017: 15 · 2016: 14 · 2015: 25 · 2014: 26 · 2013: 17 · 2012: 23
FWCI: 14.22
Type: journal article
Language: en
Open access: gold
doi.org
Licence: public-domain
creativecommons.org/licenses/by/4.0/ (vor, 3201 d)
Locations: Environmental Health Perspectives (publishedVersion, public-domain)
PubMed Central (publishedVersion, public-domain)
PubMed (publishedVersion)
Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders: U.S. Environmental Protection Agency (R01 ES013744, P42 ES05947, P01 ES012874, 83172501, R01 ES007821, R01 ES014930, RD-83172501)
Consejo Nacional de Ciencia y Tecnología (P01 ES012874, P42 ES05947, R01 ES007821, R01 ES014930, RD-83172501, 4150M9405, R01 ES013744)
National Institutes of Health (ES-00002)
National Institute of Environmental Health Sciences (P 42-ES05947, K23ES000381, R01ES014930, ES05947, P01ES012874, R01ES007821, ES014930, ES013744, ES 007821, P42ES005947, P30ES000002, K01ES014907, R01ES020268, P30-ES00002, ES 00002, RD-83172501, R01ES013744)
Topics: Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords: prenatal lead exposure, DNA methylation, umbilical cord blood, LINE-1 methylation, fetal programming, epigenetic programming, environmental toxins, developmental toxicity
MeSH terms: Base Sequence, Environmental Pollutants, Female, Fetal Blood, Humans, Lead, Mexico, Polymerase Chain Reaction, DNA Primers, Maternal Exposure, DNA Methylation

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Influence of Prenatal Lead Exposure on Genomic Methylation of Cord Blood DNA

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