By the third or fourth month, erythropoiesis moves to the spleen and liver. By the second year, it moves to the bone marrow. In humans with certain diseases and in some animals, erythropoiesis also occurs outside the bone marrow, within the spleen or liver. This is called extramedullary erythropoiesis. By age 25, the tibia and femur cease to be important sites of hematopoiesis, but the vertebrae, sternum, pelvis and ribs, and cranial bones continue to produce red blood cells throughout life.
The organ responsible for the production of erythrocytes (red blood cells) is the kidney. When this organ detects low levels of oxygen in the blood, it responds by releasing a hormone called erythropoietin, which then travels to the red bone marrow to stimulate the marrow to begin production of erythrocytes. Once the erythropoietin has begun stimulating the red bone marrow to start manufacturing red blood cells, a series of events occurs. In the bone marrow there are many special stem cells from which red blood cells can be formed. As these cells mature, they extrude their nucleus as they slowly fill with hemoglobin until they are bright red reticulocytes ready to escape the bone marrow and squeeze into the blood capillaries to begin circulating around the body.
Erythrocytes precursors, called erythroid cells, begin as pluripotential stem cells. The first cell that is recognizable as specifically leading down the red cell pathway is the proerythroblast. As development continues, the nucleus becomes somewhat smaller and the cytoplasm becomes more basophilic, due to the presence of ribosomes. In this stage the cell is called a basophilic erythroblast. The cell will continue to become smaller throughout development. As the cell begins to produce hemoglobin, the cytoplasm attracts both basic and eosin stains, and is called a polychromatophilic erythroblast. The cytoplasm eventually becomes more eosinophilic, and the cell is called an orthochromatic erythroblast. This orthochromatic erythroblast will then extrude its nucleus and enter the circulation as a reticulocyte. Reticulocytes are so named because these cells contain reticular networks of polyribosomes. As reticulocytes loose their polyribosomes they become mature red blood cells.