DNA methylation at birth potentially mediates the association between prenatal lead (Pb) exposure and infant neurodevelopmental outcomes
Year: 2021
Type: article
Abstract: Early-life lead (Pb) exposure has been linked to adverse neurodevelopmental outcomes. Recent evidence has indicated a critical role of DNA methylation (DNAm) in cognition, and Pb exposure has also been shown to alter DNAm. However, it is unknown whether DNAm is part of the mechanism of Pb neurotoxicity. This longitudinal study investigated the associations between trimester-specific (T1, T2, and T3) maternal blood Pb concentrations, gene-specific DNAm in umbilical cord blood, and infant neurodevelopmental outcomes at 12 and 24 months of age (mental development index, psychomotor development index, and behavioral rating scale of orientation/engagement and emotional regulation) among 85 mother–infant pairs from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) study. In the mediation analysis for this pilot study, P < 0.1 was considered significant. DNAm at a locus in CCSER1 (probe ID cg02901723) mediated the association between T2 Pb on 24-month orientation/engagement [indirect effect estimate 4.44, 95% confidence interval (−0.09, 10.68), P = 0.06] and emotional regulation [3.62 (−0.05, 8.69), P = 0.05]. Cg18515027 (GCNT1) DNAm mediated the association of T1 Pb [−4.94 (−10.6, −0.77), P = 0.01] and T2 Pb [−3.52 (−8.09, −0.36), P = 0.02] with 24-month EMOCI, but there was a positive indirect effect estimate between T2 Pb and 24-month psychomotor development index [1.25 (−0.11, 3.32), P = 0.09]. The indirect effect was significant for cg19703494 (TRAPPC6A) DNAm in the association between T2 Pb and 24-month mental development index [1.54 (0, 3.87), P = 0.05]. There was also an indirect effect of cg23280166 (VPS11) DNAm on T3 Pb and 24-month EMOCI [2.43 (−0.16, 6.38), P = 0.08]. These associations provide preliminary evidence for gene-specific DNAm as mediators between prenatal Pb and adverse cognitive outcomes in offspring.
Source: Current Zoology
DOI: 10.1093/eep/dvab005
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: diamond
Funders: U.S. Environmental Protection Agency, University of Michigan, National Institutes of Health, Center for Clinical and Translational Sciences, University of Texas Health Science Center at Houston, National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Center for Advancing Translational Sciences
Awards: M-CHEAR: Michigan Children's Health Exposure Analysis Resource Laboratory Hub, G1359291607, Metal Mixtures and Neurodevelopment, G2505541989, G2606127446, Fetal Lead Exposure, Genes, and Neurodevelopment, G2816684504, Prenatal and Childhood Exposure to Fluoride and Neurodevelopment, G319086767, G3579589283, G3656197451, Institutional Career Development Core, G397675506, G4016179031, G4158271349, G4267366234, Perinatal exposures, epigenetics, child obesity & sexual maturation, G4732092458, Lifecourse Exposures & Diet: Epigenetics, Maturation & Metabolic Syndrome, G5543110103, G5609688447, G5614138626, E3Gen: Multigenerational Effects of Toxicant Exposures on Life Course Health and Neurocognitive Outcomes in the ELEMENT Birth Cohorts, G6420129771, G6448097371, G660983105, G6688364618, G7328900500, G7384749199, G9000033164, G9000189254, G9000209082, Environmental Epigenomics and Precision Environmental Health, University of Michigan Training Program in Genomic Science, Stress-Air Pollution Interactions and Adolescent Neurobehavior, Michigan Nutrition Obesity Research Center, Michigan Center on Lifestage Environmental Exposures and Disease (M-LEEaD), Human Health Exposure Analysis Resource (HHEAR) Data Center
OpenAlex ID: W3171080200