This research program proposal, consisting of studies in comparative reproductive physiology, plans to test the following hypotheses with regard to intrauterine fetal growth and metabolism: 1) that in the pregnant ovine subjected to hyperthermia, intra uterine fetal growth retardation develops which is secondary to decreased placental size and function and results in asymmetrical fetal growth with specific metabolic disturbances in-utero; 2) that deprivation of material carbohydrate and fetal insulin in the ovine result in intrauterine fetal growth retardation; 3) that intrauterine fetal growth retardation in the guinea pig associated with a small placenta (runt vs pick of litter) is best described as a sequential growth retardation and is associated with major alterations in fetal fat accretion and rates of lipogenesis; 4) that the measurement of androstenedione metabolic clearance rate to estrogens in the pregnant human reflects placental blood flow and/or function and a decrease in placental flow or function may be related to intrauterine fetal growth retardation; and 5) that intrauterine growth retardation in humans may be subdivided into those associated with placentas of appropriate size and function, as well as placentas that are decreased in size and function, and that the metabolic implications in each case are quite different. Ovine placental function will be determined by the antipyrine and tritiated water techniques. Metabolic studies in the sheep will include both the measurement of net quantities of nutrients being delivered to the uterus and fetus, as well as respective utilization rates of carbohydrates and amino acids by tracer methodology. Substrate uptake by the uterus of chronically catheterized guinea pigs will be determined by application of the Pick principle coupled with uterine blood flow determinations made with radioactive microspheres. In pregnant humans, the conversion of androstenedione to estrogens will be determined by the infusion of stable isotopes. Metabolic studies in infants will include measurement of disposal rates of 13C glucose/13C leucine, as well as nitrogen balance studies. Glucose clamp methodology will be used in the carbohydrate studies. The results obtained from these studies will then be related to fetal and placental size in the various species.
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