Early-life lead exposure results in dose- and sex-specific effects on weight and epigenetic gene regulation in weanling mice. (October 2013)

• Record Type: Journal Article
• Authors: Faulk, Christopher; Barks, Amanda; Liu, Kevin; Goodrich, Jaclyn M; Dolinoy, Dana C
• Is Part Of: Epigenomics. Volume 5:Number 5(2013)
• Page Start: 487
• Page End: 500
• Publication Date: 2013-10
• Subjects: developmental origins of health and disease -- DNA methylation -- environmental epigenomics -- epigenetics -- lead -- metastable epiallele -- plasticity -- viable yellow agouti; Epigenesis -- Periodicals; Genomics -- Periodicals; Chromatin -- Periodicals; DNA -- Periodicals; 572.87
• DOI: 10.2217/epi.13.49
• Languages: English
• ISSNs: 1750-1911

Abstract

Aims: 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.Materials & 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.Conclusion: 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.