Exercise and diet interventions in obese fathers restores early embryo development and fetal weights, improving insulin sensitivity and reducing adipocyte cell size in subsequent female offspring. (#141)
Having an obese father reduces embryo development, pregnancy rates and increases the likelihood of an obese child. Rodent models have additionally showed increased birth weights and adult onset hyperinsulinemia in female offspring. Whether lifestyle interventions in the father to reduce adiposity and improve health can prevent these consequences for pregnancy and metabolic health of their daughters is unknown.
C57BL6 male mice (n=32) were fed a control diet (CD-6%-fat) or a high fat diet (HFD-21%-fat) for 10 weeks before HFD mice were allocated to either a control diet (HC), exercise (HE), combined diet/exercise intervention (HCE) or a continued HFD (HH) for a further 8 weeks. Males were mated with CD females and on-time embryo development and cell numbers determined (n=300 per group). At 8/17weeks of age, female offspring (n=12 per group) had glucose tolerance (GTT), insulin tolerance (ITT) and insulin secretion during GTT (IGT) assessed. Gonadal fat (n=6 per group) collected post-mortem (18weeks) and adipocyte size assessed. Embryology was controlled for father and GLM-ANOVA performed, offspring were matched for litter size and repeated measures ANOVA performed.
Exercise interventions in fathers (HE, HCE) increased blastocyst development (+14%, p<0.05) and cell numbers (+12%, p<0.05) compared with HH fathers. All paternal interventions restored offspring size to CD day-5 post partum. HE offspring had improved glucose tolerance (+15%, p<0.05) and insulin sensitivity (+43%, p<0.05) at 8weeks, as well as normalisation of hyperinsulinaemia (-39%, p<0.05) at 17weeks compared with HH offspring. Both HE and HC offspring displayed a reduction in adipocyte size (-42%, p<0.05) compared with HH offspring.
This study shows that the impaired embryo development and metabolic health of female offspring fathered by obese males can be improved by lifestyle interventions in the father. Suggesting that interventions to father’s health peri-conceptionlly could significantly improve pregnancy outcomes and the metabolic health of the next generation.