Obese father’s metabolic state, adiposity, and reproductive capacity indicate son’s reproductive health

Abstract

To determine whether dietary and exercise regimes in obese males can provide a novel intervention window for improving the reproductive health of the next generation. Experimental animal study. University research facilities. C57BL6 male and female mice. Mice were fed a control diet (6% fat) or high-fat diet (21% fat) for 9 weeks. After the initial feeding, high-fat-diet males were allocated to diet and/or exercise interventions for a further 9 weeks. After intervention males were mated with females fed standard chow (4% fat) before and during pregnancy. F1 sperm motility, count, morphology, capacitation, mitochondrial function, and sperm binding and weight of reproductive organs. Our primary finding was that diet intervention alone in founders improved offspring sperm motility and mitochondrial markers of sperm health (decreased reactive oxygen species and mitochondrial membrane potential), ultimately improving sperm binding. Sperm binding and capacitation was also improved in F1 males born to a combined diet and exercise intervention in founders. Founder sperm parameters and metabolic measures as a response to diet and/or exercise (i.e., lipid/glucose homeostasis, sperm count and morphology) correlated with offspring's sperm function, independent of founder treatment. This implicates paternal metabolic and reproductive status in predicting male offspring's reproductive function. This is the first study to show that improvements to both metabolic (lipids, glucose and insulin sensitivity) and reproductive function (sperm motility and morphology) in obese fathers via diet and exercise interventions can improve subsequent reproductive health in offspring.