The overall objective of the present proposal is to delineate the relationship between fetal growth rate and fetal/placental substrate balance, hormonal status and protein metabolism. To achieve a wide range of growth rates for investigation, models of intrauterine growth retardation (IUGR) and acceleration in the chronically instrumented pregnant sheep will be utilized. We hypothesize that during IUGR, reduced fetal glucose (and possibly amino acid) availability will affect a decrease in basal insulin levels, increased amino acid catabolism and reduced protein synthetic rates. The decreased rates of protein synthesis (which normally may account for in excess of 50% of the oxidative requirement) may result in decreased oxygen consumption rates in the IUGR fetal lamb. (The converse will be true during accelerated growth associated with fetal hyperglycemia, i.e., increased protein synthetic rates will effect augmented oxygen consumption.) Ultimately, alimentation of the IUGR fetus or mother with appropriate substrate (e.g., glucose) should normalize the altered fetal metabolic and growth patterns. To test these hypotheses, the following series of studies is proposed. First, we will measure fetal linear and circumferential growth, fetal/placental energy, substrate and hormonal balance and protein kinetics during normal and reduced rates of growth using the chronically instrumented fetal lamb model. Second, we will measure the same parameters of fetal growth and metabolism during accelerated rates of fetal growth as occurs during chronic hyperglycemia and hyperinsulinemia as induced by maternal uterine artery glucose infusion. Third, we will determine whether alimentation with appropriate substrate (glucose and possibly amino acids) directly to the fetus early in the course of a growth retarding insult will prevent the expected fetal metabolic changes. Fourth, we will assess whether such alimentation provided to the fetus after IUGR has been established will normalize the altered fetal protein and energy metabolism. Finally, we will assess whether alimentation provided to the mother may modify, and possibly normalize, the growth and metabolic aberrations of the IUGR fetus.
| Kaneta, M; Liechty, E A; Moorehead, H C et al. (1991) Ovine fetal and maternal glycogen during fasting. Biol Neonate 60:215-20 |
| Philipps, A F; Rosenkrantz, T S; Lemons, J A et al. (1990) Insulin-induced alterations in amino acid metabolism in the fetal lamb. J Dev Physiol 13:251-9 |
| Goodwin, G W; Gibboney, W; Paxton, R et al. (1987) Activities of branched-chain amino acid aminotransferase and branched-chain 2-oxo acid dehydrogenase complex in tissues of maternal and fetal sheep. Biochem J 242:305-8 |
