Erythropoietin transplacental passage--review of animal studies

Animal studies addressing the question does erythropoietin (EPO) cross the placenta are reviewed in a historical context. The majority of early studies using impure EPO preparations and assays of EPO's biologic activity concluded that EPO did not cross the placenta in biologically meaningful quantities. With the availability of pure recombinant EPO, direct measurement of EPO passage using radiolabeled tracers confirmed these findings in near term sheep and monkeys, but not in mice and rats. In the latter species, fetal plasma EPO levels were 7-10% of maternal plasma levels. Although not proven, it is likely that in murine species maternal EPO reaches the fetal circulation via a receptor mediated process. Even though EPO receptors have not been found in late gestation ovine and human placental tissue, this does not eliminate the possibility that EPO could traverse the placenta earlier in gestation during organogenesis. Thus while treatment of anemic women during pregnancy may have desirable maternal physiologic effects and eliminate maternal and fetal risks associated with erythrocyte transfusion, the potential for as yet unrecognized untoward fetal effects of EPO remains. In addition to future animal studies, ethically acceptable and scientifically sound studies in appropriately selected high risk groups of anemic women are needed to address this concern.