Lead (Pb) exposure is associated with a wide range of neurological deficits. Environmental exposures may impact epigenetic changes, such as DNA methylation, and can affect neurodevelopmental outcomes over the life-course. Mating mice were obtained from a genetically invariant C57BL/6J background agouti viable yellow Avy strain. Virgin dams (a/a) were randomly assigned 0 ppm (control), 2.1 ppm (low), or 32 ppm (high) Pb-acetate water two weeks prior to mating with male mice (Avy/a), and this continued through weaning. At age 10 months, cortex neuronal nuclei were separated with NeuN+ antibodies in male mice to investigate neuron-specific genome-wide promoter DNA methylation using the Roche NimbleGen Mouse 3x720K CpG Island Promoter Array in nine pooled samples (three per dose). Several probes reached p-value < 10-5, all of which were hypomethylated: 12 for high Pb (minimum false discovery rate (FDR) = 0.16, largest intensity ratio difference = −2.1) and 7 for low Pb (minimum FDR = 0.56, largest intensity ratio difference = −2.2). Consistent with previous results in bulk tissue, we observed a weak association between early-life exposure to Pb and DNA hypomethylation, with some affected genes related to neurodevelopment or cognitive function. Although these analyses were limited to males, data indicate that non-dividing cells such as neurons can be carriers of long-term epigenetic changes induced in development.
Bibliographical noteFunding Information:
Funding: This research was funded by the University of Michigan (UM) NIEHS/EPA Children’s Environmental Health and Disease Prevention Centers P20 ES018171/RD83480001 and P01 ES022844/RD83543601, and the Michigan Lifestage Environmental Exposures and Disease (M-LEEaD) NIEHS Core Center (P30 ES017885). Farooqui and Faulk were supported by UM Institutional and Individual Training Grant T32 ES007062. Dou and Bakulski were supported by grants from the National Institute of Environmental Health Sciences and the National Institute of Aging (R01 ES025531; R01 ES025574; R01 AG055406; and OD023285). The APC was funded by University of Michigan internal funds.
- DNA methylation
- In utero