title: Obesity-related DNA methylation at imprinted genes in human sperm: Results from the TIEGER study.
abstract: BACKGROUND
  Epigenetic reprogramming in mammalian gametes resets methylation marks that regulate monoallelic expression of imprinted genes. In males, this involves erasure of the maternal methylation marks and establishment of paternal-specific methylation to appropriately guide normal development. The degree to which exogenous factors influence the fidelity of methylation reprogramming is unknown. We previously found an association between paternal obesity and altered DNA methylation in umbilical cord blood, suggesting that the father's endocrine, nutritional, or lifestyle status could potentiate intergenerational heritable epigenetic abnormalities. In these analyses, we examine the relationship between male overweight/obesity and DNA methylation status of imprinted gene regulatory regions in the gametes.
  
  
  METHODS
  Linear regression models were used to compare sperm DNA methylation percentages, quantified by bisulfite pyrosequencing, at 12 differentially methylated regions (DMRs) from 23 overweight/obese and 44 normal weight men. Our study population included 69 volunteers from The Influence of the Environment on Gametic Epigenetic Reprogramming (TIEGER) study, based in NC, USA.
  
  
  RESULTS
  After adjusting for age and fertility patient status, semen from overweight or obese men had significantly lower methylation percentages at the MEG3 (β = -1.99; SE = 0.84; p = 0.02), NDN (β = -1.10; SE = 0.47; p = 0.02), SNRPN (β = -0.65; SE = 0.27; p = 0.02), and SGCE/PEG10 (β = -2.5; SE = 1.01; p = 0.01) DMRs. Our data further suggest a slight increase in DNA methylation at the MEG3-IG DMR (β = +1.22; SE = 0.59; p = 0.04) and H19 DMR (β = +1.37; SE = 0.62; p = 0.03) in sperm of overweight/obese men.
  
  
  CONCLUSIONS
  Our data support that male overweight/obesity status is traceable in the sperm epigenome. Further research is needed to understand the effect of such changes and the point of origin of DNA methylation differences between lean and overweight/obese men. Together with our earlier reports on paternal obesity and epigenetic shifts in the offspring, our studies set the groundwork for future studies investigating male gametic methylation aberrations due to paternal lifestyle factors such as obesity.
authors.affiliation: Epidemiology Research Group, Department of Public Health and Primary Care, Faculty of Medicine, KU Leuven University, 3000 Leuven, Belgium.
authors.forename: Adelheid
authors.initials: A
authors.lastname: Soubry
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC 27708 USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC 27708 USA.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC 27633 USA.
authors.forename: Cathrine
authors.initials: C
authors.lastname: Hoyo
authors.affiliation: Epidemiology Research Group, Department of Public Health and Primary Care, Faculty of Medicine, KU Leuven University, 3000 Leuven, Belgium.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Romanus
authors.affiliation: Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Fertility, Duke University Medical Center, Durham, NC 27713 USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Price
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC 27708 USA ; Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710 USA.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Murphy
mesh_terms: D000328:Adult; D019175:DNA Methylation; D018392:Genomic Imprinting; D006801:Humans; D016014:Linear Models; D008297:Male; D009765:Obesity / Q000235:genetics*; D050177:Overweight / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics; D013094:Spermatozoa / Q000378:metabolism; D055815:Young Adult
chemical_list: C094335:H19 long non-coding RNA; C498907:MEG3 non-coding RNA, human; D062085:RNA, Long Noncoding
keywords: Epigenetics; Imprinted gene; Methylation; Obesity; Sperm; TIEGER study