Early-life lead exposure results in dose- and sex-specific effects on weight and epigenetic gene regulation in weanling mice.
OBJECTIVE
Epidemiological and animal data suggest that the development of adult chronic conditions is influenced by early-life exposure-induced changes to the epigenome. This study investigates the effects of perinatal lead (Pb) exposure on DNA methylation and bodyweight in weanling mice.


METHODS
Viable yellow agouti (A(vy)) mouse dams were exposed to 0, 2.1, 16 and 32 ppm Pb acetate before conception through weaning. Epigenetic effects were evaluated by scoring coat color of A(vy)/a offspring and quantitative bisulfite sequencing of two retrotransposon-driven (A(vy) and CDK5 activator-binding protein intracisternal A particle element) and two imprinted (Igf2 and Igf2r) loci in tail DNA.


RESULTS
Maternal blood Pb levels were below the limit of detection in controls, and 4.1, 25.1 and 32.1 µg/dl for each dose, respectively. Pb exposure was associated with a trend of increased wean bodyweight in males (p = 0.03) and altered coat color in A(vy)/a offspring. DNA methylation at A(vy) and the CDK5 activator-binding protein intracisternal A-particle element was significantly different from controls following a cubic trend (p = 0.04; p = 0.01), with male-specific effects at the A(vy) locus. Imprinted genes did not shift in methylation across exposures.


CONCLUSIONS
Dose- and sex-specific responses in bodyweight and DNA methylation indicate that Pb acts on the epigenome in a locus-specific fashion, dependent on the genomic feature hosting the CpG site of interest, and that sex is a factor in epigenetic response.
Department of Environmental Health Sciences, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2200, USA.
Christopher
C
Faulk
Amanda
A
Barks
Kevin
K
Liu
Jaclyn M
JM
Goodrich
Dana C
DC
Dolinoy
D000818:Animals; D019175:DNA Methylation; D057890:Epigenomics; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D018626:Retroelements
D018626:Retroelements