Figure 4. Anatomic sites of erythropoiesis in mammals during development and pathological conditions.

A. During the course of embryonic development in human and mice, the yolk sac is the first source of erythrocytes to provide the fetus with oxygen. Throughout development, fetal liver contributes as the main source of erythropoiesis with the yolk sac regressing. At the time of birth, the bone marrow emerges as the main source of erythropoiesis with the seeding of the hematopoietic stem cells. However, a notable difference is the contribution to erythropoiesis of the spleen in the mouse till 3 months of age. In humans, the sites of erythropoiesis change over time as red blood cell production recedes in the long bones (tibia, femur) and persists in the flat bones (sternum, skull, ribs, pelvis). B. During stress erythropoiesis, the sites of erythropoiesis in the adult human are primarily the flat bones of the skull, sternum, and pelvis with minor contributions from the liver and less so from the spleen. Contributions from the liver and the spleen do not normally occur unless under pathologic disease states. In the mouse system, splenic erythropoiesis is a main feature of stress erythropoiesis with erythroid progenitors in the spleen having being well studied and described. Conversely in the rat, the spleen is a minor contributor of erythropoiesis during times of stress.