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Preconception diet or exercise intervention in obese fathers normalizes sperm microRNA profile and metabolic syndrome in female offspring
journal contribution
posted on 2015-05-01, 00:00 authored by Nicole O McPherson, Julie OwensJulie Owens, Tod Fullston, Michelle LaneObesity 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
History
Journal
American journal of physiologyVolume
308Issue
9Pagination
E805 - E821Publisher
The American Pysiological SocietyLocation
Bethesda, Md.Publisher DOI
eISSN
1522-1555Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2015 the American Physiological SocietyUsage metrics
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No categories selectedKeywords
fertilityinfertilityinterventionsobesitypaternal programmingAnimal Nutritional Physiological PhenomenaAnimalsDietFathersFemaleFertilizationInfertility, MaleMaleMetabolic SyndromeMiceMice, Inbred C57BLMice, ObeseMicroRNAsPhysical Conditioning, AnimalPregnancyPrenatal Exposure Delayed EffectsSpermatozoaTranscriptomeScience & TechnologyLife Sciences & BiomedicineEndocrinology & MetabolismPhysiologyBODY-MASS INDEXHIGH-FAT DIETTRANSGENERATIONAL INHERITANCEREPRODUCTIVE HEALTHINSULIN-RESISTANCEPATERNAL OBESITYADIPOSE-TISSUEWEIGHT-LOSSMOUSE
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