Abstract 1562 Neonatal Immunology & Hematology Poster Symposium, Monday, 5/3

Because increases in plasma erythropoietin (EPO) concentration in response to anemia in preterm infants are less than in anemic adults, inadequate EPO production has been suggested as the underlying mechanism for neonatal anemia. As an alternative explanation for these findings we have suggested that the 3- to 4-fold greater EPO clearance observed in infants compared to adults is responsible (J Appl Physiol 80:140, 1996). Since recent evidence indicates that EPO clearance is a saturable, receptor-mediated process determined by EPO-specific receptors (EPO-R) located primarily on erythroid progenitors, we hypothesized that total level EPO-R gene expression determined from freshly obtained tissues might differ in their EPO-R gene expression depending on the proportion of hematopoietic activity (with the highest hematopoietic activities expected in fetal liver and in adult bone). Tissues from 54 fetuses from 15 to 22 weeks gestation and from 27 adult transplant donors were analyzed for EPO-R gene expression by semi-quantitative reverse transcription/polymerase chain reaction. Estimated total body EPO-R gene expression was 30-fold greater per kg body weight in the fetus compared to adults. When expressed as the mean (±SEM) number of molecules of EPO-R × 103/micrograms RNA, EPO-R expression was significantly higher in fetal liver and kidney, but not in brain, lung or muscle; adult bone EPO-R expression was higher than fetuses (Table). Of the fetal tissues, only the liver demonstrated a significant inverse association of EPO-R expression with gestational age: r = -0.50 P = 0.006, n = 29. Our findings documenting an increase in total body EPO-R expression in the fetus relative to the adult are consistent with the hypothesis that EPO-R is the primary contributor to EPO's elimination and that EPO-R expression is markedly increased in fetuses. Moreover, the relatively high gene expression in the fetal liver and adult bone suggests that EPO-R expression is primarily - although not exclusively - attributable to the high density of erythroid progenitors in these tissues. Finally, the presence of EPO-R in non-erythroid tissues suggests an important role for EPO in development.

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