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Genes (Basel). 2019 Apr 4;10(4). pii: E274. doi: 10.3390/genes10040274.

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

Author information

1
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA. johndou@umich.edu.
2
Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. zafa@umich.edu.
3
Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA. zafa@umich.edu.
4
Department of Animal Science, College of Food, Agricultural, and Natural Resource Sciences, University of Minnesota, St. Paul, MN 55108, USA. cfaulk@umn.edu.
5
Department of Pediatrics, University of Minnesota Masonic Children's Hospital, Minneapolis, MN 55454, USA. barks012@umn.edu.
6
Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA. trmeier@umich.edu.
7
Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA. ddolinoy@umich.edu.
8
Department of Nutritional Sciences, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA. ddolinoy@umich.edu.
9
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA. bakulski@umich.edu.

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 NeuNâș 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.

KEYWORDS:

DNA methylation; Pb; in utero; lead; neuron

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