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

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Soubry, Adelheid

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Schildkraut, Joellen M

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Murtha, Amy

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Wang, Frances

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Huang, Zhiqing

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Bernal, Autumn

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Kurtzberg, Joanne

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Jirtle, Randy L

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Murphy, Susan K

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Hoyo, Cathrine

dc.date.accessioned

2022-03-25T17:13:46Z

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2022-03-25T17:13:46Z

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2013-02-06

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2022-03-25T17:13:45Z

dc.description.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.
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1741-7015-11-29

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1741-7015

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1741-7015

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https://hdl.handle.net/10161/24718

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eng

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Springer Science and Business Media LLC

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BMC medicine

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10.1186/1741-7015-11-29

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Animals

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Humans

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Obesity

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Preconception Injuries

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Insulin-Like Growth Factor II

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Cohort Studies

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Fathers

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DNA Methylation

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Epigenesis, Genetic

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Pregnancy

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Infant, Newborn

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Female

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Male

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RNA, Long Noncoding

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Surveys and Questionnaires

dc.title

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

dc.type

Journal article

duke.contributor.orcid

Kurtzberg, Joanne|0000-0002-3370-0703

duke.contributor.orcid

Murphy, Susan K|0000-0001-8298-7272

pubs.begin-page

29

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1

pubs.organisational-group

Duke

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Nicholas School of the Environment

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School of Medicine

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Faculty

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Clinical Science Departments

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Institutes and Centers

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Family Medicine and Community Health

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Pathology

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Pediatrics

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Family Medicine and Community Health, Prevention Research

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Duke Cancer Institute

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Environmental Sciences and Policy

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Institutes and Provost's Academic Units

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Initiatives

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Duke Innovation & Entrepreneurship

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Pediatrics, Transplant and Cellular Therapy

pubs.publication-status

Published

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11

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