Perturbation of Erythropoiesis during the Period of Early Anemia. A Model for Studying the Regulation of Erythropoiesis in the Neonatal Mammal

Abstract

The basic hypoxia-erythropoietin mechanism operating in adult mammals seems to be established already during fetal life. However, several studies indicate that regulation of erythropoiesis in the neonate differs from the adult. A significant fall in Hb occurs postnatally in almost all mammals and is termed the early anemia. Perturbation of erythropoiesis during this period offers an opportunity to distinguish between anemic-hypoxia dependent and independent regulatory mechanism of erythropoiesis in the neonatal mammal. The early anemia is iron responsive in pigs, mice, rats and rabbits. The rabbits were given iron parenterally and the mice were hypertransfused. Thus, two very different methods were used to avoid the early anemia. We have also studied untreated neonatal rats and preterm infants. The main parameters studied were: plasma erythropoiesis stimulating factor(s) (ESF), Hb, PCV, reticulocyte count, erythrocyte 2,3-diphosphoglycerate, PO2 50%, available O2, total red cell volume and weight gain. The early anemia in mice and rabbits is accompanied by a marked rise in plasma ESF, as determined by a cell culture assay. Our studies so far show that the marked rise in plasma ESF only in part is due to low Hb/PCV. The data indicate that anemic-hypoxia independent mechanisms are involved in the regulation of erythropoiesis in the neonatal mammal. In accordance with observations in preterm infants, these mechanisms could be related to the rapid growth and matruation per se. It is also notable that the start of rise in Hb/PCV in untreated mice, rats and rabbits seems to be related to the time of weaning. Together with the observed effect of iron-supplementation in the rabbit, this suggests that the rate of erythropoiesis during the period of the early anemia has been restricted by the availability of iron and/or other essential nutritional factors, and not by the production capacity of the erythron.