Influence of prenatal lead exposure on genomic methylation of cord blood DNA.
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 (109)Cd 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 (beta= -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.
Pilsner
J Richard
JR
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA. rpils@umich.edu
Hu
Howard
H
Ettinger
Adrienne
A
Sánchez
Brisa N
BN
Wright
Robert O
RO
Cantonwine
David
D
Lazarus
Alicia
A
Lamadrid-Figueroa
Héctor
H
Mercado-García
Adriana
A
Téllez-Rojo
Martha Maria
MM
Hernández-Avila
Mauricio
M
D001483:Base Sequence; D019175:DNA Methylation / Q000187:drug effects*; D017931:DNA Primers; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D006801:Humans; D007854:Lead / Q000633:toxicity*; D018811:Maternal Exposure; D008800:Mexico; D016133:Polymerase Chain Reaction
D017931:DNA Primers; D004785:Environmental Pollutants; D007854:Lead