Preconception diet or exercise interventions in obese fathers normalizes sperm microRNA profile and metabolic syndrome in female offspring

Obesity and type II diabetes are increasingly prevalent across all demographics. Paternal obesity in humans and rodents can program obesity and impaired 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 weeks (2 rounds of spermatogenesis) in obese founder males restores insulin sensitivity and normalised adiposity in female offspring. Founder diet and/or exercise also normalises abundance of X-linked sperm microRNA that target genes regulating cell cycle and apoptosis, pathways central to oocyte and early embryogenesis. Additionally obesity associated co-morbidities 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 normalise aberrant epigenetic signals in sperm and improve the metabolic health of female offspring.Nicole O McPherson, Julie A Owens, Tod Fullston, and Michelle Lan