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

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Title: Influence of Prenatal Lead Exposure on Genomic Methylation of Cord Blood DNA.
Authors: Pilsner, J. Richard1,2 rpils@umich.edu, Hu, Howard3,4,5, Ettinger, Adrienne4,5, Sáánchez, Brisa N.6, Wright, Robert O.4,5,7, Cantonwine, David3, Lazarus, Alicia1, Lamadrid-Figueroa, Héctor8, Mercado-García, Adriana9, Téllez-Rojo, Martha Maria8, Hernández-Avila, Mauricio10
Source: Environmental Health Perspectives. Sep2009, Vol. 117 Issue 9, p1466-1471. 6p. 3 Charts, 1 Graph.
Subject Terms: Physiological effects of lead, Prenatal chemical exposure, Cord blood, Methylation, DNA, Leukocytes, X-ray spectroscopy, Patella, Tibia
Geographic Terms: Mexico
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. [ABSTRACT FROM AUTHOR]
Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Influence of Prenatal Lead Exposure on Genomic Methylation of Cord Blood DNA.
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  Data: <searchLink fieldCode="AR" term="%22Pilsner%2C+J%2E+Richard%22">Pilsner, J. Richard</searchLink><relatesTo>1,2</relatesTo><i> rpils@umich.edu</i><br /><searchLink fieldCode="AR" term="%22Hu%2C+Howard%22">Hu, Howard</searchLink><relatesTo>3,4,5</relatesTo><br /><searchLink fieldCode="AR" term="%22Ettinger%2C+Adrienne%22">Ettinger, Adrienne</searchLink><relatesTo>4,5</relatesTo><br /><searchLink fieldCode="AR" term="%22Sáánchez%2C+Brisa+N%2E%22">Sáánchez, Brisa N.</searchLink><relatesTo>6</relatesTo><br /><searchLink fieldCode="AR" term="%22Wright%2C+Robert+O%2E%22">Wright, Robert O.</searchLink><relatesTo>4,5,7</relatesTo><br /><searchLink fieldCode="AR" term="%22Cantonwine%2C+David%22">Cantonwine, David</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Lazarus%2C+Alicia%22">Lazarus, Alicia</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Lamadrid-Figueroa%2C+Héctor%22">Lamadrid-Figueroa, Héctor</searchLink><relatesTo>8</relatesTo><br /><searchLink fieldCode="AR" term="%22Mercado-García%2C+Adriana%22">Mercado-García, Adriana</searchLink><relatesTo>9</relatesTo><br /><searchLink fieldCode="AR" term="%22Téllez-Rojo%2C+Martha+Maria%22">Téllez-Rojo, Martha Maria</searchLink><relatesTo>8</relatesTo><br /><searchLink fieldCode="AR" term="%22Hernández-Avila%2C+Mauricio%22">Hernández-Avila, Mauricio</searchLink><relatesTo>10</relatesTo>
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  Data: <searchLink fieldCode="DE" term="%22Physiological+effects+of+lead%22">Physiological effects of lead</searchLink><br /><searchLink fieldCode="DE" term="%22Prenatal+chemical+exposure%22">Prenatal chemical exposure</searchLink><br /><searchLink fieldCode="DE" term="%22Cord+blood%22">Cord blood</searchLink><br /><searchLink fieldCode="DE" term="%22Methylation%22">Methylation</searchLink><br /><searchLink fieldCode="DE" term="%22DNA%22">DNA</searchLink><br /><searchLink fieldCode="DE" term="%22Leukocytes%22">Leukocytes</searchLink><br /><searchLink fieldCode="DE" term="%22X-ray+spectroscopy%22">X-ray spectroscopy</searchLink><br /><searchLink fieldCode="DE" term="%22Patella%22">Patella</searchLink><br /><searchLink fieldCode="DE" term="%22Tibia%22">Tibia</searchLink>
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  Data: <searchLink fieldCode="DE" term="%22Mexico%22">Mexico</searchLink>
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  Label: Abstract
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  Data: 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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1289/ehp.0800497
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        Text: English
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      – SubjectFull: Physiological effects of lead
        Type: general
      – SubjectFull: Prenatal chemical exposure
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      – SubjectFull: Cord blood
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