This program consists of 8 projects centered around studies of perinatal metabolism, fetal and placental growth, and cardiopulmonary adaptation. The studies of fetal and maternal carbohydrate metabolism (Project I) include studies in both hypo- and hyperinsulinemic states, define the conditions for fetal gluconeogenesis and the adaptations of the maternal liver to pregnancy. The studies in newborn lambs (II) include the relative roles of glucose and galactose intake in glycogen synthesis and the impact of the 2 dietary transitions on protein synthesis and turnover. The studies of fetal amino acid metabolism (III) include the evaluation of potential fetal growth factors, i.e. somatomedin I, growth hormone, and insulin, upon leucine flux to CO2 and to protein synthesis, and address the ontogenic changes in protein synthesis during early fetal life. The impact of dietary changes in the mother on potential fetal growth factors and protein synthetic rates will be evaluated. Project IV will study the metabolic changes induced in the mother by labor onset. The relationship between maternal metabolism and abnormal labor will be assessed. The studies will also consider the potential role of the placenta as a metabolic buffer to the fetus during labor. The possibility that the placenta becomes hypermetabolic during labor, sparing nutrients and oxygen for the fetus, will be investigated. The adaptations of normal and abnormal fetal pulmonary circulations and of the transitional circulation will be studied (V) with focus on the chronicity of the adaptive responses. Interorgan cycling of substrates will be studied (VI) using the fetal hindlimb and liver with emphasis on lactate kinetics. The possibility that lactate metabolism may be relatively unregulated will be investigated utilizing lactate clamp methodology. In Project VII, the studies of early fetal life will center around metabolic and placental function studies performed in the midgestation ewe when the fetus is 5%-10% of its term weight, providing far more precise ontogenic scaling of metabolic processes to body size. Project VIII will study the relationship between fetal and placental growth, body composition and caloric accretion, and the rates of glycogen and lipid synthesis. Comparisons will be made within litters for the guinea pig and rabbit so that fetal growth and composition can be compared in relationship to variations in placental size and perfusion.
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