title: Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort.
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.
authors: Duke Cancer Institute, Duke University Medical Center 2715, Durham, NC 27710, USA. adelheid.soubry@hotmail.com
authors: Adelheid
authors: A
authors: Soubry
authors: Joellen M
authors: JM
authors: Schildkraut
authors: Amy
authors: A
authors: Murtha
authors: Frances
authors: F
authors: Wang
authors: Zhiqing
authors: Z
authors: Huang
authors: Autumn
authors: A
authors: Bernal
authors: Joanne
authors: J
authors: Kurtzberg
authors: Randy L
authors: RL
authors: Jirtle
authors: Susan K
authors: SK
authors: Murphy
authors: Cathrine
authors: C
authors: Hoyo
mesh_terms: D000818:Animals; D015331:Cohort Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005220:Fathers; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008297:Male; D009765:Obesity / Q000150:complications*; D047489:Preconception Injuries; D011247:Pregnancy; D062085:RNA, Long Noncoding / Q000235:genetics; D011795:Surveys and Questionnaires
chemical_list: C094335:H19 long non-coding RNA; C035170:IGF2 protein, human; D062085:RNA, Long Noncoding; D007335:Insulin-Like Growth Factor II
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