title: Preconception diet or exercise intervention in obese fathers normalizes sperm microRNA profile and metabolic syndrome in female offspring.
abstract: Obesity and type 2 diabetes are increasingly prevalent across all demographics. Paternal obesity in humans and rodents can program obesity and impair insulin sensitivity in female offspring. It remains to be determined whether these perturbed offspring phenotypes can be improved through targeted lifestyle interventions in the obese father. Using a mouse model, we demonstrate that diet or exercise interventions for 8 wk (2 rounds of spermatogenesis) in obese founder males restores insulin sensitivity and normalized adiposity in female offspring. Founder diet and/or exercise also normalizes abundance of X-linked sperm microRNAs that target genes regulating cell cycle and apoptosis, pathways central to oocyte and early embryogenesis. Additionally, obesity-associated comorbidities, including inflammation, glucose intolerance, stress, and hypercholesterolemia, were good predictors for sperm microRNA abundance and offspring phenotypes. Interventions aimed at improving paternal metabolic health during specific windows prior to conception can partially normalize aberrant epigenetic signals in sperm and improve the metabolic health of female offspring.
authors.affiliation: School of Paediatrics and Reproductive Health, Discipline of Obstetrics and Gynaecology, Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia; Freemasons Center for Men's Health, University of Adelaide, Adelaide, South Australia, Australia; and nicole.mcpherson@adelaide.edu.au.
authors.forename: Nicole O
authors.initials: NO
authors.lastname: McPherson
authors.affiliation: School of Paediatrics and Reproductive Health, Discipline of Obstetrics and Gynaecology, Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia;
authors.forename: Julie A
authors.initials: JA
authors.lastname: Owens
authors.affiliation: School of Paediatrics and Reproductive Health, Discipline of Obstetrics and Gynaecology, Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia;
authors.forename: Tod
authors.initials: T
authors.lastname: Fullston
authors.affiliation: School of Paediatrics and Reproductive Health, Discipline of Obstetrics and Gynaecology, Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia; Freemasons Center for Men's Health, University of Adelaide, Adelaide, South Australia, Australia; and Monash IVF Group, Melbourne, Victoria, Australia.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lane
mesh_terms: D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D004032:Diet; D005220:Fathers; D005260:Female; D005306:Fertilization / Q000502:physiology; D007248:Infertility, Male / Q000235:genetics / Q000517:prevention & control; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D035683:MicroRNAs / Q000235:genetics*; D009765:Obesity / Q000235:genetics; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000378:metabolism; D013094:Spermatozoa / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D035683:MicroRNAs
keywords: fertility; infertility; interventions; obesity; paternal programming