Based on animal experiments, a switch of the erythropoietin (EPO) prod
uction site from the liver in the fetus to the kidneys in the adult ha
s been postulated. To study the switch in humans, we have quantitated
EPO mRNA expression in liver, kidney, spleen, and bone marrow of human
fetuses and neonates by means of a competitive polymerase chain react
ion (PCR), Tissue samples from 66 routine postmortem examinations were
obtained. EPO mRNA was expressed in 97% of the tissue specimen derive
d from the liver (n = 66) and in 93% of those from the kidneys (17 wee
ks of gestation until 18 months after birth; n = 59). For the first ti
me the EPO gene was found expressed in vivo in human spleen (96% of 64
samples) and in fetal and neonatal bone marrow (81% of 21 samples). E
PO mRNA expression in the kidneys increased significantly beyond 30 we
eks of gestation (P < .05). Although there was a slight decrease in EP
O mRNA content per g liver tissue towards birth, the liver accounted f
or about 80% of the total body EPO mRNA. The contribution of the splee
n and bone marrow were minor compared with liver and kidneys. Our resu
lts indicate that in humans the liver is the primary site of EPO gene
expression not only in fetal, but also in neonatal life. A significant
increase of renal EPO mRNA expression after 30 weeks of gestation mig
ht indicate the beginning switch. (C) 1998 by The American Society of
Hematology.