Fetal programming of insulin-like growth factor (IGF)-I and IGF-binding protein-3: evidence for an altered response to undernutrition in late gestation following exposure to periconceptual undernutrition in the sheep

It has been demonstrated in several animal models that undernutrition in ut ero has significant long lasting effects on subsequent fetal and postnatal development. To address the hypothesis that the insulin-like growth factors (IGFs) may mediate such effects, our study examined whether a period of pe riconceptual maternal undernutrition could have a lasting influence on the IGF axis in the fetal sheep. Ewes were either allowed to feed ad libitum or kept undernourished from day 60 prior to mating until day 30 after concept ion, and then both groups were allowed to feed nd libitum. These groups wer e further divided at day 105 of gestation, either being fed nn libitum or u ndernourished until day 115 of gestation. Fetal and maternal blood samples were obtained at both day 105 and 115 of gestation. We describe the develop ment of a specific homologous RIA to measure ovine IGF-binding protein-3 (I GFBP-3) in fetal and maternal sheep plasma. Fetal plasma IGFBP-3 and IGF-I concentrations were significantly (P<0.05) reduced at day 115 of gestation after maternal undernutrition. The fetal plasma IGFBP-2 levels were unchang ed. The degree of reduction in fetal plasma IGFBP-3 and IGF-I between day 1 05 and 115 of gestation as a response to acute maternal undernutrition was significantly greater (P<0.05) in fetuses of mothers receiving low periconc eptual nutrition. The response of maternal plasma IGFBP-3 and IGF-I to unde rnutrition did not depend on the level of periconceptual nutrition. Western blot data indicate that changes in either maternal or fetal plasma IGFBP-3 concentrations were not the result of increased proteolytic activity. Thes e results suggest that exposure to maternal periconceptual undernutrition r eprograms IGFBP-3 and IGF-I regulation in the developing sheep fetus, alter ing its response to undernutrition in late gestation.