Nonerythropoietic roles of erythropoietin in the fetus and neonate.

Epo was once regarded as a cytokine with only hematopoietic effects. It is now clear that the distributions of Epo and Epo-R are more widespread in the developing human. Epo-R is widely distributed during early fetal development, leading to speculation that Epo acts in concert with other growth factors to optimize growth and development. Areas in which Epo has important recognized effects are on endothelial cells, and in the developing heart, gastrointestinal tract, and brain. It may also be important in the regulation of vascular growth during the menstrual cycle, and in the stimulation of testosterone production in men. Epo and Epo-R are prominent in the brain during fetal development, leading to speculation that they play an important role in neurodevelopment. There are also promising data regarding rEpo as a possible neuroprotective agent in such conditions as hypoxia, because it decreases programmed cell death induced during such adverse conditions. It is unlikely, however, that rEpo crosses the blood-brain barrier in normal premature infants, and it is not clear whether the CNS effects of rEpo, should it cross the blood-brain barrier, are harmful or beneficial in the setting of a developing brain.