Perinatal Lead (Pb) Exposure and Cortical Neuron-Specific DNA Methylation in Male Mice
AbstractLead (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. View Full-Text
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Dou, J.F.; Farooqui, Z.; Faulk, C.D.; Barks, A.K.; Jones, T.; Dolinoy, D.C.; Bakulski, K.M. Perinatal Lead (Pb) Exposure and Cortical Neuron-Specific DNA Methylation in Male Mice. Genes 2019, 10, 274.
Dou JF, Farooqui Z, Faulk CD, Barks AK, Jones T, Dolinoy DC, Bakulski KM. Perinatal Lead (Pb) Exposure and Cortical Neuron-Specific DNA Methylation in Male Mice. Genes. 2019; 10(4):274.Chicago/Turabian Style
Dou, John F.; Farooqui, Zishaan; Faulk, Christopher D.; Barks, Amanda K.; Jones, Tamara; Dolinoy, Dana C.; Bakulski, Kelly M. 2019. "Perinatal Lead (Pb) Exposure and Cortical Neuron-Specific DNA Methylation in Male Mice." Genes 10, no. 4: 274.
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