Prenatal lead (Pb) exposure is associated with differential placental DNA methylation and hydroxymethylation in a human population

Prenatal lead (Pb) exposure is associated with adverse developmental outcomes and to epigenetic alterations such as DNA methylation and hydroxymethylation in animal models and in newborn blood. Given the importance of the placenta in foetal development, we sought to examine how prenatal Pb exposure...

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Published in:Epigenetics 2022-12, Vol.17 (13), p.2404-2420
Main Authors: Tung, Pei Wen, Kennedy, Elizabeth M., Burt, Amber, Hermetz, Karen, Karagas, Margaret, Marsit, Carmen J.
Format: Article
Language:English
Subjects:
DNA Methylation
Epigenesis, Genetic
epigenetics
Epigenomics
EWAS
Female
Humans
hydroxymethylation
Infant
Infant, Newborn
lead
Lead - metabolism
Lead - toxicity
Maternal Exposure - adverse effects
placenta
Placenta - metabolism
Pregnancy
Research Paper
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creator Tung, Pei Wen
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description Prenatal lead (Pb) exposure is associated with adverse developmental outcomes and to epigenetic alterations such as DNA methylation and hydroxymethylation in animal models and in newborn blood. Given the importance of the placenta in foetal development, we sought to examine how prenatal Pb exposure was associated with differential placental DNA methylation and hydroxymethylation and to identify affected biological pathways linked to developmental outcomes. Maternal (n = 167) and infant (n = 172) toenail and placenta (n = 115) samples for prenatal Pb exposure were obtained from participants in a US birth cohort, and methylation and hydroxymethylation data were quantified using the Illumina Infinium MethylationEPIC BeadChip. An epigenome-wide association study was applied to identify differential methylation and hydroxymethylation associated with Pb exposure. Biological functions of the Pb-associated genes were determined by overrepresentation analysis through ConsensusPathDB. Prenatal Pb quantified from maternal toenail, infant toenail, and placenta was associated with 480, 27, and 2 differentially methylated sites (q 
doi_str_mv 10.1080/15592294.2022.2126087
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Prenatal Pb quantified from maternal toenail, infant toenail, and placenta was associated with 480, 27, and 2 differentially methylated sites (q &lt; 0.05), respectively, with both increases and decreases associated with exposure. Alternatively, we identified 2, 1, and 14 differentially hydroxymethylated site(s) associated with maternal toenail, infant toenail, and placental Pb, respectively, with most showing increases in hydroxymethylation with exposure. Significantly overrepresented pathways amongst genes associated with differential methylation and hydroxymethylation (q &lt; 0.10) included mechanisms pertaining to nervous system and organ development, calcium transport and regulation, and signalling activities. 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subjects DNA Methylation
Epigenesis, Genetic
epigenetics
Epigenomics
EWAS
Female
Humans
hydroxymethylation
Infant
Infant, Newborn
lead
Lead - metabolism
Lead - toxicity
Maternal Exposure - adverse effects
placenta
Placenta - metabolism
Pregnancy
Research Paper
title Prenatal lead (Pb) exposure is associated with differential placental DNA methylation and hydroxymethylation in a human population
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