Adult exercise effects on oxidative stress and reproductive programming in male offspring

22 Introduction/Purpose. Exercise improves health but few data are available regarding benefits of 23 exercise in offspring exposed to developmental programming. There is currently a worldwide 24 epidemic of obesity. Obesity in pregnant women predisposes offspring to obesity. Maternal 25 obesity has well documented effects on offspring reproduction. Few studies address ability of 26 offspring exercise to reduce adverse outcomes. We observed increased oxidative stress and 27 impaired sperm function in rat offspring of obese mothers. We hypothesized that regular 28 offspring exercise reverses adverse effects of maternal obesity on offspring sperm quality and 29 fertility. Methods. Female Wistar rats ate chow (C) or high energy, obesogenic diet (MO) from 30 weaning through lactation, bred at postnatal day (PND) 120 and ate their pregnancy diet until 31 weaning. All offspring ate C diet from weaning. Five male offspring (different litters) wheel-ran 32 15 min, 5 times/ week from PND 330 to 450, and were euthanized at PND 450. Results. 33 Average distance run per session was lower in MO offspring who had higher body weight, 34 adiposity index and gonadal fat and showed increases in testicular oxidative stress biomarkers. 35 Sperm from MO offspring had reduced antioxidant enzyme activity, lower sperm quality and 36 fertility. Exercise in MO offspring decreased testicular oxidative stress, increased sperm 37 antioxidant activity and sperm quality and improved fertility. Conclusions. Exercise intervention 38 has beneficial effects on adiposity index, gonadal fat, oxidative stress markers, sperm quality and 39 fertility. Thus, regular physical exercise in male MO offspring recuperates key male reproductive 40 functions even at advanced age: it’s never too late. 41