Pflügers Archiv

, Volume 427, Issue 1–2, pp 157–161 | Cite as

Lack of transport of erythropoietin across the human placenta as studied by an in vitro perfusion system

  • Antoine Malek
  • Ruth Sager
  • Kai -Uwe Eckardt
  • Christian Bauer
  • Henning Schneider
Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands


The transfer of human recombinant erythropoietin (rhEPO) from the maternal to the fetal side was investigated using the technique of in vitro perfusion of an isolated cotyledon of human placenta, with recirculation of the perfusate (130 ml) in separate closed maternal and fetal circuits. rhEPO (221–512 U), together with [14C]BSA (bovine serum albumin, 44.8 kBq or 2,688,000 dpm), was added to the maternal circuit only. Despite a considerably lower molecular weight of EPO mol. wt.=30,400 Da) compared to BSA (mol. wt.= 69,000 Da), no difference was found in their transfer across the placenta from the maternal to the fetal side, which was very low for both macromolecules. The total transfer of rhEPO derived from the concentration measured in the samples taken from the fetal circuit at the end of 4–5 h of perfusion, was in the range of 0.04% of the amount initially added to the maternal compartment. A similar amount of transfer was determined for [14C]BSA (0.04–0.07%,n=12). In conclusion, by direct determination in a dually in vitro perfused human placental cotyledon, no significant transfer of rhEPO from the maternal to the fetal side could be shown.

Key words

Erythropoietin Placental transfer Human In vitro perfusion 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Anagnostou A, Lee ES, Kessimian N, Levinson R, Steiner M (1990) Erythropoietin has a mitogenic and positive chemotactic effect on endothelial cells. Proc Natl Acad Sci USA 87: 5978–5982Google Scholar
  2. 2.
    Bowen D, Ehmer B, Neubert P, Lewis T, Jacobs A (1991) The clearance of a single i.v. bolus of recombinant human erythropoietin from the serum of patients with myelodysplastic syndromes and its effects on erythropoiesis. Exp Hematol 19:613–616Google Scholar
  3. 3.
    Cotes PM, Canning CE, Lind T (1983) Changes in serum immunoreactive erythropoietin during the menstrual cycle and normal pregnancy. Br J Obstet Gynaecol 90:304–311Google Scholar
  4. 4.
    Eckardt KU, Kurtz A, Hirth P, Scigalla P, Wieczorek L, Baue C(1988) Evaluation of the stability of human erythropoietin in samples for radioimmunoassay. Klin Wochenschr 66:241–245Google Scholar
  5. 5.
    Edwards D, Jones CJP, Sibley CP, Nelson DM (1993) Paracellular permeability pathways in the human placenta: a quantitative and morphological study of maternal-fetal transfer of horseradish peroxidase. Placenta 14:63–73Google Scholar
  6. 6.
    Eichhorn KH, Bauer C, Eckardt KU, Zimmermann R, Huch A, Huch R (1993) Lack of associations between fetal and maternal serum-erythropoietin at birth. Eur J Obstet Gynecol Reprod Biol50:47–52Google Scholar
  7. 7.
    Flaharty KK, Caro J, Erslev A, Whalen J, Morris EM, Bjornsson TD, Vlasses PH (1990) Pharmacokinetics and erythropoietic response to human recombinant erythropoietin in healthy men. Clin Pharmacol Ther 47:557–564Google Scholar
  8. 8.
    Gitlin D, Kumate J, Urrusti J, Morales C (1964) The selectivity of the human placenta in the transfer of plasma proteins from mother to fetus. J Clin Invest 43:1938–1951Google Scholar
  9. 9.
    Hedley R, Bradbury MWB (1980) Transport of polar nonelectrolyts across the intact and perfused guinea-pig placenta. Placenta 1:277–285Google Scholar
  10. 10.
    Much A, Eichhorn KH, Danko J, Lauener PA, Huch R (1992) Recombinant human erythropoietin in the treatment of postpartum anaemia. Obstet Gynecol 80:127–131Google Scholar
  11. 11.
    Ireland R, Abbas A, Thilaganathan B, Melbye O, Snjiders R, Layton M, Nicolaides KH (1992) Fetal and maternal erythropoietin levels in normal pregnancy. Fetal Diagn Ther 7:21–25Google Scholar
  12. 12.
    Jacobson LO, Marks EK, Gaston EO (1959) Studies on erythropoiesis. XII. The effect of transfusion-induced polycythemia in the mother on the fetus. Blood 14:644–653Google Scholar
  13. 13.
    Jelkmann W (1992) Erythropoietin: structure, control of production and function. Physiol Rev 72:449–489Google Scholar
  14. 14.
    Koury MJ, Bondurant MC, Graber SE, Sawyer ST (1988) Erythropoietin messenger RNA levels in developing mice and transfer of125I-erythropoietin by the placenta. J Clin Invest 82:154–159Google Scholar
  15. 15.
    Krantz SB (1991) Erythropoietin. Blood 77:419–434Google Scholar
  16. 16.
    Macdougall IC, Neubert P, Coles GA, Roberts DE, Dharmasena AD, Williams JD (1989) Pharmacokinetics of recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis. Lanccet I: 425–427Google Scholar
  17. 17.
    Malek A, Sager R, Ugele B, Schneider H (1992) Transport of IgG and its subclasses across the perfused human placenta in vitro. Placenta 13:A42Google Scholar
  18. 18.
    Masuda S, Nagao M, Takahata K, Konishi Y, Gallyas F Jr, Tabira T, Sasaki R (1993) Functional erythropoietin receptor of the cells with neural characteristics. Comparison with receptor properties of erythroid cells. J Biol Chem 268:11208–11216Google Scholar
  19. 19.
    Pekonen F, Rosenlöf K, Rutanen EM, Fyhrquist F (1987) Erythropoietin binding sites in human foetal tissues. Acta Endocrinol (Copenh) 116:561–567Google Scholar
  20. 20.
    Sawada K, Krantz SB, Sawyer ST, Civin CI (1988) Quantitation of specific binding of erythropoietin to human erythroid colony-forming cells. J Cell Physiol 137:337–345Google Scholar
  21. 21.
    Sawyer ST, Krantz SB, Sawada K (1989) Receptors for erythropoietin in mouse and human erythroid cells and placenta. Blood 74:103–109Google Scholar
  22. 22.
    Schneider H (1991) The role of the placenta in nutrition of the human fetus. Am J Obstet Gynecol 77:419–434Google Scholar
  23. 23.
    Schneider H, Panigel M, Dancis J (1972) Transfer across the perfused human placenta of antipyrine, sodium and leucine. Am J Obstet Gynecol 114:822–828Google Scholar
  24. 24.
    Thomas RM, Canning CE, Cotes PM, Linch DC, Rodeck CH, Rossiter CE, Huehns ER (1983) Erythropoietin and cord blood haemoglobin in the regulation of human fetal erythropoiesis. Br J Obstet Gynaecol 90:795–800Google Scholar
  25. 25.
    Thorp JA, O'Conner T, Callenbach J, Cohen GR, Yeast JD, Albin J, Plapp F (1991) Hyporegenerative anaemia associated with intrauterine transfusion in rhesus hemolytic disease. Am J Obstet Gynecol 165:79–81Google Scholar
  26. 26.
    Widness JA, Sawyer ST, Schmidt RL, Chestnut DH (1991) Lack of maternal to fetal transfer of125I-labelled erythropoietin in sheep. J Dev Physiol 15:139–143Google Scholar
  27. 27.
    Zanjani ED, Peterson EN, Gordon AS, Wasserman LR (1974) Erythropoietin production in the fetus: role of the kidney and maternal anaemia. J Lab Clin Med 83:281–287Google Scholar
  28. 28.
    Zanjasni ED, Slotnick N, Clemons GK (1990) Erythropoietin does not cross the placenta. Clin Res 38:236AGoogle Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Antoine Malek
    • 1
  • Ruth Sager
    • 1
  • Kai -Uwe Eckardt
    • 2
  • Christian Bauer
    • 3
  • Henning Schneider
    • 1
  1. 1.Department of Obstetrics and GynecologyUniversity of BerneBerneSwitzerland
  2. 2.Institute of PhysiologyUniversity of RegensburgGermany
  3. 3.Institute of PhysiologyUniversity of ZurichSwitzerland

Personalised recommendations