The long-term objective is to understand the physiologic regulation of blood volume in the fetus. Because total red blood cell volume is an important component of blood volume, the objective requires that the regulation of red cell volume be understood. Thus, the proposed studies focus on the regulation of fetal red cell production using the chronically catheterized ovine fetus as an animal model. These studies are important not only because very little is currently known about the regulation of red cell production in the fetus but also because anemia in the human fetus and newborn are associated with high rates of morbidity and mortality. The first series of studies will determine red cell production rates in normal fetuses and determine whether these production rates depend upon fetal age, plasma iron, or plasma erythropoietin concentration. We will also determine whether red cell size and/or size distribution varies with fetal age or red cell production rate. The second study will determine the effects of iron and/or erythropoietin supplementation on red cell production in the normal fetus. The objective is to find an optimal combination of iron and erythropoietin to maximize red cell production rates. A third study will determine the ability of the fetus to augment red cell production rates during anemia and will determine whether this depends on availability of endogenous iron or erythropoietin. The hypothesis is that iron availability is the major limiting factor in red cell production under anemic conditions. A fourth study will focus on enhancing red cell production in the anemic fetus by supplementing iron and/or erythropoietin. We hypothesize that exogenous iron will allow the fetus to greatly augment red cell production rates. The fifth study will explore the hypotheses that red cell life expectancy in the fetus is one-tenth of that in the adult and that total red cell volume will correlate inversely with red cell life expectancy. For the above studies, we are also hypothesizing that mean red cell volume depends on fetal age, type of hemoglobin present, rate of red cell production, and iron as well as erythropoietin availability. Collectively, the proposed studies will greatly enhance our understanding of the factors which regulate hematopoiesis in the fetus. This information is needed in order to improve current therapies for treating anemia in the human fetus and newborn as well as for understanding basic physiological processes.
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