title: Paternal obesity induces metabolic and sperm disturbances in male offspring that are exacerbated by their exposure to an "obesogenic" diet.
abstract: Obesity and related comorbidities are becoming increasingly prevalent globally. In mice preconception paternal exposure to a high fat diet (HFD) impairs the metabolic and reproductive health of male offspring, despite their control diet (CD) consumption. However, offspring share lifestyle, including diet, with parents. We assessed if male offspring from HFD fathers have a heightened susceptibility to HFD-induced metabolic and reproductive derangements. This 2 × 2 design saw founder males (F0) and their offspring (F1) fed either a HFD or a nutritionally matched CD. Regardless of paternal diet, HFD fed male offspring had greater total body weight and adiposity. Offspring sired by a HFD male and fed a HFD were the heaviest, had the greatest adiposity and had the greatest concentration of serum cholesterol, triglyceride, HDL, and NEFA compared with CD sired/fed littermates. A synergistic increase in serum insulin was unmasked by both father/son HFD consumption, concomitant with increased sera glucose. Either a paternal or offspring HFD was associated with similar reductions to offspring sperm motility. Whereas sperm ROS concentrations and sperm-oocyte binding saw detrimental effects of both F0 HFD and F1 HFD with an interaction evident between both, culminating in the most impaired sperm parameters in this group. This indicates that metabolic and fertility disturbances in male offspring sired by HFD fathers are exacerbated by a "second-hit" of exposure to the same obesogenic environment postnatally. If translatable to human health, this suggests that adverse reproductive and metabolic outcomes may be amplified across generations through a shared calorie dense diet, relevant to the current worldwide obesity epidemic.
authors: Discipline of Obstetrics & Gynaecology, Robinson Research Institute, Research Centre for Reproductive Health, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia tod.fullston@adelaide.edu.au.
authors: Tod
authors: T
authors: Fullston
authors: Discipline of Obstetrics & Gynaecology, Robinson Research Institute, Research Centre for Reproductive Health, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia Freemasons Foundation Centre for Men's Health, The University of Adelaide, Adelaide, SA, Australia.
authors: Nicole O
authors: NO
authors: McPherson
authors: Discipline of Obstetrics & Gynaecology, Robinson Research Institute, Research Centre for Reproductive Health, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia.
authors: Julie A
authors: JA
authors: Owens
authors: Discipline of Obstetrics & Gynaecology, Robinson Research Institute, Research Centre for Reproductive Health, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia.
authors: Wan Xian
authors: WX
authors: Kang
authors: Discipline of Obstetrics & Gynaecology, Robinson Research Institute, Research Centre for Reproductive Health, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia.
authors: Lauren Y
authors: LY
authors: Sandeman
authors: Discipline of Obstetrics & Gynaecology, Robinson Research Institute, Research Centre for Reproductive Health, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia Monash IVF Group, Melbourne, Vic., Australia.
authors: Michlle
authors: M
authors: Lane
keywords: Metabolic syndrome; obesogenic environment; paternal obesity; paternal programming; second‐hit; subfertility