The prevention of acute and chronic fetal hypoxia and fetal growth disorders depends upon a better understanding of placental and fetal respiratory physiology and metabolism from early to late pregnancy. The long-term goal of this project is to identify and study the factors that regulate the exchange of respiratory gases and metabolic substrates between maternal blood, placenta and fetal blood. The specific aims are: (1) to study placental and fetal oxygen, carbohydrate and amino acid metabolism in early fetal life; (2) to test the effect of both even and uneven occlusion of the umbilical circulation on placental O2 transfer and fetal oxygenation; (3) to study the chronic regulation of fetal oxygenation by comparing placental respiratory function in A and B hemoglobin homozygous ewes that carry either singletons or twins; (4) to study the role of fetal insulin on placental and fetal metabolism; and (5) to study rates and sites of fructose utilization in the ovine fetus. The studies will be performed in chronic sheep preparations. The maternal-placental-fetal metabolic exchange will be quantitated by using techniques of blood flow measurement, chemical analysis of maternal arterial, uterine venous, umbilical arterial, venous blood, and tracer methodology.