title: Diet-induced paternal obesity in the absence of diabetes diminishes the reproductive health of two subsequent generations of mice.
abstract: BACKGROUND
  Obesity and related conditions, notably subfertility, are increasingly prevalent. Paternal influences are known to influence offspring health outcome, but the impact of paternal obesity and subfertility on the reproductive health of subsequent generations has been overlooked.
  
  
  METHODS
  A high-fat diet (HFD) was used to induce obesity but not diabetes in male C57Bl6 mice, which were subsequently mated to normal-weight females. First-generation offspring were raised on a control diet and their gametes were investigated for signs of subfertility. Second-generation offspring were generated from both first generation sexes and their gametes were similarly assessed.
  
  
  RESULTS
  We demonstrate a HFD-induced paternal initiation of subfertility in both male and female offspring of two generations of mice. Furthermore, we have shown that diminished reproductive and gamete functions are transmitted through the first generation paternal line to both sexes of the second generation and via the first generation maternal line to second-generation males. Our previous findings that founder male obesity alters the epigenome of sperm, could provide a basis for the developmental programming of subfertility in subsequent generations.
  
  
  CONCLUSIONS
  This is the first observation of paternal transmission of diminished reproductive health to future generations and could have significant implications for the transgenerational amplification of subfertility observed worldwide in humans.
authors.affiliation: Research Centre for Reproductive Health , Discipline of Obstetrics and Gynaecology, Level 3 Medical School South, Robinson Institute, University of Adelaide, Adelaide, South Australia 5005, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Fullston
authors.forename: N O
authors.initials: NO
authors.lastname: Palmer
authors.forename: J A
authors.initials: JA
authors.lastname: Owens
authors.forename: M
authors.initials: M
authors.lastname: Mitchell
authors.forename: H W
authors.initials: HW
authors.lastname: Bakos
authors.forename: M
authors.initials: M
authors.lastname: Lane
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D005260:Female; D007246:Infertility / Q000209:etiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications*; D047489:Preconception Injuries