Erythropoiesis in the fetus is controlled by erythropoietin (Ep). To d
etermine the role of maternal Ep in this process, we used catheterized
preparations of sheep and monkey fetuses to assess the ability of Ep
administered to the mother to cross the placental barrier into the fet
us. Ep was injected into pregnant sheep (3,600 IU/sheep) or monkeys (8
00-2,000 IU/animal) as a single intravenous dose, or into sheep in int
ravenous doses of 2,000 IU once every 12 h for a total of 4 injections
. Maternal and fetal blood samples for Ep and reticulocyte determinati
ons were obtained before and at intervals after Ep injections. The adm
inistration of Ep resulted in significant increases in maternal circul
ating Ep levels in sheep and monkeys. Despite the presence of high lev
els of maternal Ep, however, no increase in fetal plasma Ep levels was
detected. The administration of Ep to the mother caused significant i
ncreases in reticulocyte production in the mother but not the fetus; i
njection of Ep directly to the fetus stimulated fetal erythropoiesis.
These results demonstrate that Ep does not cross the placenta into the
fetus even under conditions of chronically elevated maternal Ep level
s, and suggest that red cell production in the fetus is regulated by E
p produced from sites within the fetus.