Uteroplacental insufficiency is the major cause of intrauterine growth restriction in Western society and is associated with cardiorenal disease which is exacerbated with “second hits” such as pregnancy and overweight/obesity. We reported that F2 fetuses have nephron deficits which contribute to the development of F2 high blood pressure. This study determined if F2 male nephron deficits of mothers born small are exacerbated by a maternal high fat diet (HFD) and whether endurance exercise training can prevent these deficits.
Uteroplacental insufficiency was induced by bilateral uterine artery ligation (Restricted) or sham (Control) surgery on E18 in Wistar-Kyoto rats. Female offspring were fed a chow or high fat (43% kcals from fat) diet from 5 weeks to mating (20 weeks) and throughout pregnancy. Female rats were exercised on a treadmill 4 weeks before mating and throughout pregnancy. Male fetal nephron number was quantified using unbiased stereology and fetal and placental weights were measured at E20.
Restricted and Control female rats that were exposed to a HFD were heavier with more dorsal fat than females on a chow diet. Exercise prevented dorsal fat gain in Restricted HFD compared to sedentary. F2 male nephron deficit was present in mothers born small regardless of diet (-18-45%). A HFD reduced F2 male nephron number in Control mothers (-32%). Exercise prevented the HFD induced nephron deficits in F2 males of both Control and Restricted mothers. Despite no treatment effect on placental weight, exercise prevented the reduced fetal weight in females born small.
We demonstrated that females born small are at a greater risk of increased adiposity. F2 male fetal nephron deficits in mothers exposed to a HFDwere prevented by the lifestyle intervention of endurance exercise. This may prevent the development of F2 high blood pressure.