title: Paternal under-nutrition programs metabolic syndrome in offspring which can be reversed by antioxidant/vitamin food fortification in fathers.
abstract: There is an ever increasing body of evidence that demonstrates that paternal over-nutrition prior to conception programs impaired metabolic health in offspring. Here we examined whether paternal under-nutrition can also program impaired health in offspring and if any detrimental health outcomes in offspring could be prevented by micronutrient supplementation (vitamins and antioxidants). We discovered that restricting the food intake of male rodents reduced their body weight, fertility, increased sperm oxidative DNA lesions and reduced global sperm methylation. Under-nourished males then sired offspring with reduced postnatal weight and growth but somewhat paradoxically increased adiposity and dyslipidaemia, despite being fed standard chow. Paternal vitamin/antioxidant food fortification during under-nutrition not only normalised founder oxidative sperm DNA lesions but also prevented early growth restriction, fat accumulation and dyslipidaemia in offspring. This demonstrates that paternal under-nutrition reduces postnatal growth but increases the risk of obesity and metabolic disease in the next generation and that micronutrient supplementation during this period of under-nutrition is capable of restoring offspring metabolic health.
authors.affiliation: Discipline of Obstetrics and Gynaecology, School of Medicine, Robinson Research Institute, University of Adelaide, South Australia, 5005, Australia.|Freemasons Centre for Men's Health, University of Adelaide, South Australia, 5005, Australia.
authors.forename: Nicole O
authors.initials: NO
authors.lastname: McPherson
authors.affiliation: Discipline of Obstetrics and Gynaecology, School of Medicine, Robinson Research Institute, University of Adelaide, South Australia, 5005, Australia.
authors.forename: Tod
authors.initials: T
authors.lastname: Fullston
authors.affiliation: Discipline of Obstetrics and Gynaecology, School of Medicine, Robinson Research Institute, University of Adelaide, South Australia, 5005, Australia.
authors.forename: Wan Xian
authors.initials: WX
authors.lastname: Kang
authors.affiliation: Discipline of Obstetrics and Gynaecology, School of Medicine, Robinson Research Institute, University of Adelaide, South Australia, 5005, Australia.
authors.forename: Lauren Y
authors.initials: LY
authors.lastname: Sandeman
authors.affiliation: Discipline of Paediatrics, School of Medicine, Robinson Research Institute, The University of Adelaide, South Australia 5005, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Corbett
authors.affiliation: Discipline of Obstetrics and Gynaecology, School of Medicine, Robinson Research Institute, University of Adelaide, South Australia, 5005, Australia.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Owens
authors.affiliation: Discipline of Obstetrics and Gynaecology, School of Medicine, Robinson Research Institute, University of Adelaide, South Australia, 5005, Australia.|Monash IVF Group, Melbourne, Victoria, 3168, Australia.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lane
mesh_terms: D050154:Adiposity; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001823:Body Composition; D047108:Embryonic Development; D005260:Female; D005527:Food, Fortified; D018703:Founder Effect; D007248:Infertility, Male / Q000209:etiology / Q000235:genetics; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D044342:Malnutrition / Q000150:complications / Q000235:genetics*; D024821:Metabolic Syndrome / Q000097:blood / Q000209:etiology / Q000235:genetics*; D008810:Mice, Inbred C57BL; D000072740:Paternal Inheritance; D017382:Reactive Oxygen Species / Q000378:metabolism; D013076:Sperm Count; D013081:Sperm Motility
chemical_list: D000975:Antioxidants; D007328:Insulin; D020738:Leptin; D008055:Lipids; D017382:Reactive Oxygen Species