The ontogeny of the biological role and production of erythropoietin.

In has been long recognized that erythropoiesis in adults is under control of erythropoietin, a glycoprotein produced mainly by adult kidneys in inverse relation to oxygen availability. Increasing evidence indicates nowadays that EPO is also an essential growth factor for red cell precursors at different sites of fetal erythropoiesis. The primary site of EPO production during fetal and neonatal life is the liver, and the fetus has been shown to be able to increase EPO production in response to hypoxia through intrinsic oxygen sensing mechanisms of hepatocytes. Thus despite different sites of both erythropoiesis and EPO production a similar oxygen dependent feedback control of red cell formation appears to operate during all stages of development. EPO levels in fetal blood are potentially useful parameters of fetal stress, and, as in adults, the availability of recombinant EPO raises the possibility to modulate erythropoiesis in the perinatal period.