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

BMC Medicine

Cathrine Hoyo²  Susan K Murphy⁴  Randy L Jirtle¹  Joanne Kurtzberg³  Autumn Bernal¹  Zhiqing Huang⁴  Frances Wang⁷  Amy Murtha⁶  Joellen M Schildkraut⁵  Adelheid Soubry⁷ 

[1] Department of Radiation Oncology, Duke University Medical Center 3433, Durham, NC 27710, USA;Department of Obstetrics and Gynecology, Division of Clinical Epidemiology, Duke University Medical Center 2914, Durham, NC 27710, USA;Department of Pediatrics, Duke University Medical Center 3350, Durham, NC 27710, USA;Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center 91012, Durham, NC 27708, USA;Department of Community and Family Medicine, Duke University Medical Center 104006, Durham, NC 27710, USA;Division of Maternal and Fetal Medicine, Department of Obstetrics and Gynecology, Duke University Medical Center, 4022 Hospital South, Durham, NC 27705, USA;Duke Cancer Institute, Duke University Medical Center 2715, Durham, NC 27710, USA

关键词: Epidemiology;    Newborn Epigenetics Study;    offspring;    obesity;    IGF2;    DNA methylation;    Epigenetics;   

Others  :  857203
DOI  :  10.1186/1741-7015-11-29

 received in 2012-04-19, accepted in 2013-02-06,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Soubry et al; licensee BioMed Central Ltd.

【 图 表 】

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