Tissue distribution of erythropoietin and erythropoietin receptor in the developing human fetus.
OBJECTIVE
Erythropoietin receptors (Epo-R) have been demonstrated on several nonhematopoietic cell types in animal models and in cell culture. Our objective was to determine the tissue distribution and cellular specificity of erythropoietin (Epo) and its receptor in the developing human fetus.


METHODS
The expression of Epo and Epo-R mRNA was ascertained by RT-PCR for organs ranging in maturity from 5 to 24 weeks postconception. The cellular location of protein immunoreactivity was then determined using specific antiEpo and antiEpo-R antibodies. Antibody specificity was established by Western analysis.


RESULTS
mRNA for Epo and Epo-R was found in all organs in the first two trimesters. Immunolocalization of Epo was limited to the liver parenchymal cells, kidney interstitial cells and proximal tubules, neural retina of the eye, and adrenal cortex. As development progressed, immunoreactivity in the kidney became more prominent. In contrast, immunoreactivity for Epo-R was widespread throughout the body, in cell types including endothelial cells, myocardiocytes, macrophages, retinal cells, cells of the adrenal cortex and medulla, as well as in small bowel, spleen, liver, kidney, and lung.


CONCLUSIONS
The distribution of Epo and its receptor is more widespread in the developing human than was initially postulated. Epo-R is expressed on many cell types during early fetal development, leading us to speculate that Epo acts in concert with somatic growth and development factors during this period. Further investigation is required to understand the nonhematopoietic role of Epo during human development.
Juul
S E
SE
Department of Pediatrics, University of Florida College of Medicine, JHMHC, Gainesville 32610-0296, USA.
Yachnis
A T
AT
Christensen
R D
RD
D000302:Adrenal Cortex / Q000737:chemistry / Q000196:embryology; D015153:Blotting, Western; D005314:Embryonic and Fetal Development; D004921:Erythropoietin / Q000032:analysis* / Q000235:genetics; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000737:chemistry / Q000196:embryology; D008099:Liver / Q000737:chemistry / Q000196:embryology; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D017467:Receptors, Erythropoietin / Q000032:analysis* / Q000235:genetics; D012160:Retina / Q000737:chemistry / Q000196:embryology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution
D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D004921:Erythropoietin