Erythropoietin and hypoxia inducible factor-1 expression in the mid-trimester human fetus.
OBJECTIVE
Infants born prematurely lack a normal response to anemia and fail to increase erythropoietin (Epo) production despite an apparent need for improved tissue oxygenation. This anemia may involve a deficiency in the fetal and premature kidney to produce Epo. To evaluate fetal Epo production, Epo and hypoxia inducible factor-1 (HIF) mRNA expression was measured in the mid-trimester human fetus.


METHODS
Fetal liver and kidney samples were obtained at 11-22 wk of gestation. RNA was isolated and reverse transcribed from snap-frozen specimens. Epo and HIF cDNA concentrations were determined using real-time polymerase chain reaction (PRISM). Epo cDNA concentrations were standardized to HIF concentrations present in each sample.


RESULTS
HIF concentrations remained constant during gestation in kidney and liver samples. Epo cDNA concentrations in kidney did not change from 12 to 22 wk (8.4 +/- 3.4 fg Epo pg(-1) HIF cDNA, 4.8 +/- 1.4, 2.6 +/- 0.4, and 4.2 +/- 1.8 at 11-14, 15-16, 17-19, and 20-22 wk of gestation, respectively), while Epo cDNA concentrations in liver increased with gestation (74.5 +/- 31.9 fg pg(-1) HIF, 23.8 +/- 6.5, 96.4 +/- 19.2 and 276.1 +/- 28.5 at 12-14, 15-16, 17-19 and 20-22 wk of gestation, respectively, p < 0.05, 20-22 wk of gestation liver samples vs all other gestations). Concentrations were 5-20-fold higher in liver than in kidney in each gestational group (p < 0.01, liver vs kidney).


CONCLUSIONS
HIF concentrations did not change with gestation in liver or kidney. The human fetal kidney produced approximately 5% of the total Epo mRNA measured during the second trimester. It remains to be determined how Epo production by these tissues is affected by premature birth.
Ohls
R K
RK
Department of Pediatrics, Division of Neonatology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131-5311, USA. rohls@unm.edu
D000704:Analysis of Variance; D001483:Base Sequence; D018076:DNA, Complementary / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D004920:Erythropoiesis / Q000502:physiology*; D004921:Erythropoietin / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D005333:Fetus / Q000737:chemistry*; D006413:Hematopoietic System / Q000196:embryology*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007668:Kidney / Q000196:embryology / Q000378:metabolism*; D008099:Liver / Q000196:embryology / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D012016:Reference Values; D012680:Sensitivity and Specificity; D014157:Transcription Factors
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D004921:Erythropoietin