Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort - PubMed (original) (raw)

Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort

Adelheid Soubry et al. BMC Med. 2013.

Abstract

Background: Data from epidemiological and animal model studies suggest that nutrition during pregnancy may affect the health status of subsequent generations. These transgenerational effects are now being explained by disruptions at the level of the epigenetic machinery. Besides in vitro environmental exposures, the possible impact on the reprogramming of methylation profiles at imprinted genes at a much earlier time point, such as during spermatogenesis or oogenesis, has not previously been considered. In this study, our aim was to determine associations between preconceptional obesity and DNA methylation profiles in the offspring, particularly at the differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene.

Methods: We examined DNA from umbilical cord blood leukocytes from 79 newborns, born between July 2005 and November 2006 at Duke University Hospital, Durham, NC. Their mothers participated in the Newborn Epigenetics Study (NEST) during pregnancy. Parental characteristics were obtained via standardized questionnaires and medical records. DNA methylation patterns at two DMRs were analyzed by bisulfite pyrosequencing; one DMR upstream of IGF2 (IGF2 DMR), and one DMR upstream of the neighboring H19 gene (H19 DMR). Multiple regression models were used to determine potential associations between the offspring's DNA methylation patterns and parental obesity before conception. Obesity was defined as body mass index (BMI) ≥30 kg/m².

Results: Hypomethylation at the IGF2 DMR was associated with paternal obesity. Even after adjusting for several maternal and newborn characteristics, we observed a persistent inverse association between DNA methylation in the offspring and paternal obesity (β-coefficient was -5.28, P = 0.003). At the H19 DMR, no significant associations were detected between methylation patterns and paternal obesity. Our data suggest an increase in DNA methylation at the IGF2 and H19 DMRs among newborns from obese mothers, but a larger study is warranted to further explore the potential effects of maternal obesity or lifestyle on the offspring's epigenome.

Conclusions: While our small sample size is limited, our data indicate a preconceptional impact of paternal obesity on the reprogramming of imprint marks during spermatogenesis. Given the biological importance of imprinting fidelity, our study provides evidence for transgenerational effects of paternal obesity that may influence the offspring's future health status.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Methylation at the IGF2 and H19 DMRs in the offspring by parental obesity. The graphs represent the mean estimated methylation values of 69 newborns at the IGF2 DMR, and 70 newborns at the H19 DMR. The IGF2 DMR results are based on 14 obese fathers and 25 obese mothers; the results at the H19 DMR are based on 15 obese fathers and 23 obese mothers. For each exposure the differences of the least square means of methylation percentages are shown at each CpG site (bold), as well as standard errors (SE) and _P_-values. Bars represent standard errors.

Figure 2

Figure 2

Offspring's mean methylation % at the IGF2 DMR by BMI of the parents. The predicted methylation means at IGF2 DMR are plotted by BMI of the father (upper graph), and BMI of the mother (lower graph); adjusted for maternal age, smoking status, BMI of the other parent, the newborn's birth weight and gender.

Comment in

Similar articles

Cited by

References

    1. McKay JA, Mathers JC. Diet induced epigenetic changes and their implications for health. Acta Physiol (Oxf) 2011;202:103–118. doi: 10.1111/j.1748-1716.2011.02278.x. - DOI - PubMed
    1. Baker J, Liu JP, Robertson EJ, Efstratiadis A. Role of insulin-like growth factors in embryonic and postnatal growth. Cell. 1993;75:73–82. - PubMed
    1. Chao W, D'Amore PA. IGF2: epigenetic regulation and role in development and disease. Cytokine Growth Factor Rev. 2008;19:111–120. doi: 10.1016/j.cytogfr.2008.01.005. - DOI - PMC - PubMed
    1. Boissonnas CC, Abdalaoui HE, Haelewyn V, Fauque P, Dupont JM, Gut I, Vaiman D, Jouannet P, Tost J, Jammes H. Specific epigenetic alterations of IGF2-H19 locus in spermatozoa from infertile men. Eur J Hum Genet. 2010;18:73–80. doi: 10.1038/ejhg.2009.117. - DOI - PMC - PubMed
    1. Kerjean A, Dupont JM, Vasseur C, Le Tessier D, Cuisset L, Paldi A, Jouannet P, Jeanpierre M. Establishment of the paternal methylation imprint of the human H19 and MEST/PEG1 genes during spermatogenesis. Hum Mol Genet. 2000;9:2183–2187. doi: 10.1093/hmg/9.14.2183. - DOI - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources