The first erythrocytes contain nuclei and derive from stem cells (BFU/CFU-E) that arise in the blood islands of the umbilical vesicle. Centrally lying cells of these blood islands join up thereby into nucleus-containing, large erythroblasts, whereas those peripherally located become endothelial cells. One also calls this extraembryonic phase of the blood formation megaloblastic eryhropoiesis.

This extraembryonal erythropoiesis is supplanted by thee embryonic erythropoiesis, which arises in the liver. These stem cells have their origin in the aorto-gonado-mesonephros region. The erythrocytes that arise in the liver are nucleus-free - in contrast to those formed outside the embryo - and are produced there up to the 28th week of pregnancy-

A small portion is also formed in the spleen (green in Figure 3). This hepatolienal phase dominates the second trimenon of the pregnancy.

In the last trimenon the bone marrow is the most important hematopoietic organ (myeloid phase of the erythropoiesis).

Fig. 3 - Proportions of the entire erythropoiesis in the blood forming organs

Umbilical vesicle
Bone marrow

Fig. 3

This diagram shows the approximate contributions of the various blood forming organs during pregnancy.

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On the erythrocyte surface membrane there are many blood group attributes, among them the well-known A and B antigenes of the ABO system as well as the rhesus factor.

How to use this interactive diagram?

After starting, if you put the mouse cursor on sensitive zones of the picture (e.g., on BFU-E or CFU-E), you will obtain an enlarged picture and explanatory text to the individual concepts.

The erythropoietic stem cells are formed by the myeloid cell series. They are large, mitotically active cells of the BFU-E cell family. They have a large nucleus and the cytoplasm is basophilic.
With further stimulation, pronormoblasts form that begin with hemoglobin synthesis. The hemoglobin cannot as yet be recognized with routine cytological analysis. These cells still have lots of uncondensed chromatin in the cell nucleus, many ribosomes and contain a high amount of m-RNA globin.
The proliferation ability of the basophilic normoblasts decreases; the chromatin begins to condense in the nucleus. The cell shrinks and the first indications of globin production can be detected.
In this stage globin in the cytoplasm can be revealed using special stains. The cell nucleus becomes increasingly pyknotic and the protein synthesis of the rough endoplasmic reticulum (rER) in the cytoplasm decreases.
In an orthochromatic normoblast the hemoglobin production is almost complete and the cytoplasm is increasingly colored with acidophilic dyes. The rER has almost completely disappeared and the cell nucleus is increasingly pyknotic.
In the orthochromatic normoblast stage the cellular nucleus is ejected.
Young nucleus-free cells of this series exhibit netlike structures when stained with supravital colors and for this reason they are known as reticulocytes.
Mature, fully differentiated erythrocytes possess hardly any cell organelles, but are fully packed with hemoglobin.
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 Overview of erythropoiesis


  • Number of erythrocytes per ml blood: ca. 5 millions
  • Diameter of the erythrocytes: 7.5 µm
  • Life expectancy: ca.120 days (at birth ca. 40-70 days)


Hemoglobin in human erythrocytes consists of 2 paired globin chains that are arranged around a heme that, for its part, can bind oxygen..

While only hemoglobin of the Hb Gower 1 (ζ2ε2) type with ζ and ε chains is formed in the blood islands of the umbilical vesicle, the mature erythrocyte of the hepatic phaseε exhibits mainly HbF (α2γ2), the globin of which possesses α and γ chains and represents the most important fetal hemoglobinγ

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The transition from Hb Gower 1 to HbF takes place in steps in that both hemoglobins with α2γ2 chains --> Hb Gower 2 as well as such with ζ2γ2 chains --> Hb Portland can be found in the intermediate phase. The genetic information for the synthesis of the individual globin chains is found on chromosomes 11 and 16 (interactive diagram).

Following birth, the fetal HbF (α2γ2) is slowly replaced by the adult HbA1 (α2β2). This consists of alpha and beta chains and represents the most important adult hemoglobin. In addition there is still a small portion of HbA2(α2δ2) that exhibits δ chains instead of β ones.

Fig. 4 - The formation of various Hb-chains during the pregnancy

Fig. 4

Synthesis of the globin chains over the course of the pregnancy. In the embryonic period the ε and ζ globin chains dominate. They are, though, rapidly taken over by α and γ globin chains. Towards the end of the pregnancy, the γ chains of the fetal hemoglobin are slowly replaced by the β chains (adult hemoglobin).