Regulation of pre-natal haemopoiesis: evidence for negative feedback control of erythropoiesis in the foetal mouse.

The effects of medium conditioned by erythrocytes on in vitro differentiation of mouse prenatal erythroblasts were examined. Haem synthesis was inversely proportional to the concentration of erythrocyte-conditioned medium (ECM) in either presence or absence of erythropoietin (EP), but concentrations of ECM which limited haem synthesis to 50% of normal had no effect on changes in erythroblast numbers. ECM reduced uridine incorporation into RNA and limited the rise in incorporation due to stimulation by EP. ECM enhanced thymidine incorporation into DNA. This enhancement was additive with that due to EP, but appeared earlier. Thymidine labelling indices of liver cells were not changed by ECM in vitro. Serum from polycythaemic animals limited haem synthesis by EP stimulated foetal liver cells in vitro. These observations provide evidence for susceptibility of foetal liver erythroblasts to negative feedback control of differentiation, dependent on the concentration of circulating erythrocytes. Characteristic changes in kinetics of prenatal erythropoiesis in vivo can also be related to increasing erythrocyte concentration.