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INTRODUCTION

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SUMMARY

During embryogenesis, hematopoiesis occurs in spatially and temporally distinct sites, including the extraembryonic yolk sac, the fetal liver, and the preterm marrow. The development of primitive erythroblasts in the yolk sac is critical for embryonic survival. Primitive erythroblasts differentiate within the vascular network rather than in the extravascular space and circulate as nucleated cells. Although it is widely assumed that primitive red cells remain nucleated throughout their life span, primitive erythroblasts ultimately enucleate upon terminal differentiation. After 7 weeks of gestation, hematopoietic progenitors are no longer detected in the yolk sac. Hematopoietic stem cells emerge from major arterial vessels at 5 weeks of gestation. The liver serves as the primary source of red cells from the 9th to the 24th week of gestation. Like primitive erythropoiesis in the yolk sac, definitive erythropoiesis in the fetal liver is necessary for continued survival of the embryo. In contrast to the yolk sac, where hematopoiesis is restricted to maturing primitive erythroid, macrophage, and megakaryocytic cells, hematopoiesis in the fetal liver consists of definitive erythroid, megakaryocyte, and multiple myeloid, as well as lymphoid lineages. Hematopoietic cells are first seen in the marrow of the 10- to 11-week embryo, and they remain confined to the diaphyseal regions of long bones until 15 weeks of gestation. Lymphopoiesis is present in the lymph plexuses and the thymus beginning at 9 weeks of gestation. Yolk sac stem cells were first thought to seed the liver and eventually the marrow. However, later experiments in avian and amphibian embryos indicate that the hematopoietic stem cells that seed the marrow arise within the body of the embryo proper rather than from the yolk sac. The aorta-gonad-mesonephros (AGM) region generates hematopoietic stem cells that seed the liver and the marrow to provide lifelong hematopoiesis. Hemoglobin (Hgb) Gower-1 (ζ2ε2) is the major hemoglobin in embryos younger than 5 weeks. Hgb F (α2γ2) is the major hemoglobin of fetal life. The fetal hemoglobin concentration in blood decreases after birth by approximately 3 percent per week and is generally less than 2 to 3 percent of the total hemoglobin by 6 months of age. The mean hemoglobin level in cord blood at term is 16.8 g/dL, with 95 percent of the values falling between 13.7 and 20.1 g/dL. The red cells of the newborn are macrocytic, with a mean cell volume in excess of 110 fL/cell. The red cell, hemoglobin, and hematocrit values decrease only slightly during the first week after birth, but decline more rapidly in the following 5 to 8 weeks, producing the physiologic anemia of the newborn. The absolute number of neutrophils in the blood of term and premature infants is usually greater than that found in older children. Segmented neutrophils are the predominant leukocytes in the first few days after birth. As their number decreases, the lymphocyte becomes the most numerous cell type and remains so during the first 4 years of ...

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