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Genes 2019, 10(4), 274; https://doi.org/10.3390/genes10040274

Perinatal Lead (Pb) Exposure and Cortical Neuron-Specific DNA Methylation in Male Mice

1
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA
2
Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
3
Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA
4
Department of Animal Science, College of Food, Agricultural, and Natural Resource Sciences, University of Minnesota, St. Paul, MN 55108, USA
5
Department of Pediatrics, University of Minnesota Masonic Children’s Hospital, Minneapolis, MN 55454, USA
6
Department of Nutritional Sciences, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA
*
Authors to whom correspondence should be addressed.
Received: 4 February 2019 / Revised: 25 March 2019 / Accepted: 29 March 2019 / Published: 4 April 2019
(This article belongs to the Special Issue Epigenetics, Environment, and Brain Disorders)
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Abstract

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. View Full-Text
Keywords: lead; Pb; DNA methylation; neuron; in utero lead; Pb; DNA methylation; neuron; in utero
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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.

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