Skip to main content
SpringerLink
Log in

Oxygen and Placental Vascular Development

  • Chapter
Hypoxia

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 474))

Abstract

Human embryogenesis takes place in a hypoxic environment because the trophoblast shell excludes entry of maternal blood. The first fetal-placental villi develop as trophoblast sprouts. These are invaded by allantoic mesoderm to form secondary villi and are transformed, by vasculogenesis, into tertiary villi. The placental barrier to maternal blood is gradually breached between 8–12 weeks of gestation, due to invasion of placental-bed uteroplacental spiral arteries by the extravillous trophoblast (EVT). Placental oxygen tension thus rises and a phase of branching angiogenesis continues until 24 weeks. Thereafter a gradual shift takes place favoring non-branching angiogenesis. Gas-exchanging terminal villi thus form which are essential for rapid fetal growth and development of a high-flow, low-resistance fetal-placental circulation.

Inadequate invasion of the uteroplacental spiral arteries by EVT results in placental ischemia and the development of obstetrical complications - preeclampsia and/or intrauterine growth restriction (IUGR). Placental villi often show evidence of continued branching angiogenesis, as is the case with anemic pregnancy, and pregnancy at high altitude. These structural alterations may reflect continued hypoxia-driven activity of vascular endothelial growth factor (VEGF). By contrast, a minority of severe early-onset IUGR pregnancies exhibit reduced fetal-placental blood flow with elongated maldeveloped villous capillaries. Placenta-like growth factor (P1GF) expression is increased while trophoblast proliferation is reduced, suggesting “hyperoxia” in the placental villous tree. IUGR may thus have two phenotypes - a more common hypoxic and a rarer hyperoxic type. While this concept is gaining acceptance, we have no insight as to the initiating mechanism(s).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ahmed, A., C. Dunk, D. Kniss, and M. Wilkes. Role of VEGF receptor-1 (Flt-1) in mediating calcium-dependent nitric oxide release and limiting DNA synthesis in human trophoblast cells. Lab Invest 76: 779–791, 1997.

    PubMed  CAS  Google Scholar 

  2. Bower, S., S. Bewley, and S. Campbell. Improved prediction of preeclampsia by two-stage screening of uterine arteries using the early diastolic notch and color Doppler imaging. Obstet Gynecol 82: 78–83, 1993.

    PubMed  CAS  Google Scholar 

  3. Burton, G.J. and E. Jauniaux. Sonographic, stereological and Doppler flow velocimetric assessments of placental maturity. Br J Obstet Gynaecol 102: 818–825, 1995.

    Article  PubMed  CAS  Google Scholar 

  4. Burton, G.J., O.S. Reshetnikova, A.P. Milovanov, and O.V. Teleshova. Stereological evaluation of vascular adaptations in human placental villi to differing forms of hypoxic stress. Placenta 17: 49–55, 1996.

    Article  PubMed  CAS  Google Scholar 

  5. Cacciatore, B., E. Halmesmaki, R. Kaaja, K. Teramo, and O. Ylikorkala. Effects of transdermal nitroglycerin on impedance to flow in the uterine, umbilical, and fetal middle cerebral arteries in pregnancies complicated by preeclampsia and intrauterine growth retardation. Am J Obstet Gynecol 179: 140–145, 1998.

    Article  PubMed  CAS  Google Scholar 

  6. Cao, Y., H. Chen, L. Zhou, M.K. Chiang, B. Anand-Apte, J.A. Weatherbee, Y. Wang, F. Fang, J.G. Flanagan, and M.L. Tsang. Heterodimers of placenta growth factor/vascular endothelial growth factor. Endothelial activity, tumor cell expression, and high affinity binding to Flk-1/KDR. JBiol Chem 271: 3154–3162, 1996.

    Article  CAS  Google Scholar 

  7. Castellucci, M., M. Scheper, I. Scheffen, A. Celona, and P. Kaufmann. The development of the human placental villous tree. Anat Embryo! (Berl) 181: 117–128, 1990.

    CAS  Google Scholar 

  8. Chang, T.C., S.C. Robson, J.A. Spencer, and S. Gallivan. Identification of fetal growth retardation: comparison of Doppler waveform indices and serial ultrasound measurements of abdominal circumference and fetal weight. Obstet Gynecol 82: 230–236, 1993.

    PubMed  CAS  Google Scholar 

  9. Chappell, L. and S. Bewley. Pre-eclamptic toxaemia: the role of uterine artery Doppler. Br J Obstet Gynaecol 105: 379–382, 1998.

    Article  PubMed  CAS  Google Scholar 

  10. Cheung, C.Y. Vascular endothelial growth factor: possible role in fetal development and placental function. J Soc Gynecol Investig 4: 169–177, 1997.

    Article  PubMed  CAS  Google Scholar 

  11. Clark, D.E., S.K. Smith, D. Licence, A.L. Evans, and D.S. Charnock-Jones. Comparison of expression patterns for placenta growth factor, vascular endothelial growth factor (VEGF), VEGF-B and VEGF-C in the human placenta throughout gestation. J Endocrinol 159: 459–467, 1998.

    Article  PubMed  CAS  Google Scholar 

  12. Cooper, J.C., A.M. Sharkey, D.S. Charnock-Jones, C.R. Palmer, and S.K. Smith. VEGF mRNA levels in placentae from pregnancies complicated by preeclampsia [see comments]. Br J Obstet Gynaecol 103: 1191–1196, 1996.

    Article  PubMed  CAS  Google Scholar 

  13. Cross, J.C. Formation of the placenta and extraembryonic membranes [In Process Citation]. Ann N YAcad Sci 857: 23–32, 1998.

    Article  CAS  Google Scholar 

  14. Cross, J.C., Z. Werb, and S.J. Fisher. Implantation and the placenta: key pieces of the development puzzle. Science 266: 1508–1518, 1994.

    Article  PubMed  CAS  Google Scholar 

  15. Evans, P.W., T. Wheeler, F.W. Anthony, and C. Osmond. A longitudinal study of maternal serum vascular endothelial growth factor in early pregnancy. Hum Reprod 13: 1057–1062, 1998.

    Article  PubMed  CAS  Google Scholar 

  16. Fisk, N.M., N. MacLachlan, C. Ellis, Y. Tannirandorn, H.M. Tonge, and C.H. Rodeck. Absent end-diastolic flow in first trimester umbilical artery [letter]. Lancet 2: 1256–1257, 1988.

    Article  PubMed  CAS  Google Scholar 

  17. Fox, H. Effect of hypoxia on trophoblast in organ culture. A morphologic and autoradiographic study. Am JObstet Gynecol 107: 1058–1064, 1970.

    Google Scholar 

  18. Francis, S.T., K.R. Duncan, R.J. Moore, P.N. Baker, I.R. Johnson, and P.A. Gowland. Non-invasive mapping of placental perfusion. Lancet 351: 1397–1399, 1998.

    Article  PubMed  CAS  Google Scholar 

  19. Grannum, P.A., R.L. Berkowitz, and J.C. Hobbins. The ultrasonic changes in the maturing placenta and their relation to fetal pulmonic maturity. Am J Obstet Gynecol 133: 915–922, 1979.

    PubMed  CAS  Google Scholar 

  20. Hendricks, S.K., T.K. Sorensen, K.Y. Wang, J.M. Bushnell, E.M. Seguin, and R.W. Zingheim. Doppler umbilical artery waveform indices--normal values from fourteen to forty-two weeks. Am J Obstet Gynecol 161: 761–765, 1989.

    PubMed  CAS  Google Scholar 

  21. Hitschold, T.P. Doppler flow velocity waveforms of the umbilical arteries correlate with intravillous blood volume. Am J Obstet Gynecol 179: 540–543, 1998.

    Article  Google Scholar 

  22. Hunter, P.J., B.J. Swanson, M.A. Haendel, G.E. Lyons, and J.C. Cross. Mrj encodes a DnaJ-related co-chaperone that is essential for murine placental development. Development 126: 1247–1258, 1999.

    PubMed  CAS  Google Scholar 

  23. Huppertz, B., H.G. Frank, J.C. Kingdom, F. Reister, and P. Kaufmann. Villous cytotrophoblast regulation of the syncytial apoptotic cascade in the human placenta. Histochem Cell Biol 110: 495–508, 1998.

    Article  PubMed  CAS  Google Scholar 

  24. Jackson, M.R., E.W. Carney, S.J. Lye, and J.W. Ritchie. Localization of two angiogenic growth factors (PDECGF and VEGF) in human placentae throughout gestation. Placenta 15: 341–353, 1994.

    Article  PubMed  CAS  Google Scholar 

  25. Jackson, M.R., T.M. Mayhew, and P.A. Boyd. Quantitative description of the elaboration and maturation of villi from 10 weeks of gestation to term. Placenta 13: 357–370, 1992.

    Article  PubMed  CAS  Google Scholar 

  26. Jackson, M.R., T.M. Mayhew, and J.D. Haas. On the factors which contribute to thinning of the villous membrane in human placentae at high altitude. I. Thinning and regional variation in thickness of trophoblast. Placenta 9: 1–8, 1988.

    Article  PubMed  CAS  Google Scholar 

  27. Jackson, M.R., A.J. Walsh, R.J. Morrow, J.B. Mullen, S.J. Lye, and J.W. Ritchie. Reduced placental villous tree elaboration in small-for-gestational-age pregnancies: relationship with umbilical artery Doppler waveforms. Am J Obstet Gynecol 172: 518–525, 1995.

    Article  PubMed  CAS  Google Scholar 

  28. Jaffe, R., E. Jauniaux, and J. Hustin. Maternal circulation in the first-trimester human placenta--myth or reality? Am J Obstet Gynecol 176: 695–705, 1997.

    Article  PubMed  CAS  Google Scholar 

  29. Johanson, R., S.W. Lindow, C. van der Elst, Z. Jaquire, S. van der Westhuizen, and A. Tucker. A prospective randomised comparison of the effect of continuous 02 therapy and bedrest on fetuses with absent end-diastolic flow on umbilical artery Doppler waveform analysis. Br J Obstet Gynaecol 102: 662–665, 1995.

    Article  PubMed  CAS  Google Scholar 

  30. Kadyrov, M., G. Kosanke, J. Kingdom, and P. Kaufmann. Increased fetoplacental angiogenesis during first trimester in anaemic women. Lancet 352: 1747–1749, 1998.

    Article  PubMed  CAS  Google Scholar 

  31. Karsdorp, V.H., J.M. van Vugt, H.P. van Geijn, P.J. Kostense, D. Arduini, N. Montenegro, and T. Todros. Clinical significance of absent or reversed end diastolic velocity waveforms in umbilical artery. Lancet 344: 1664–1668, 1994.

    Article  PubMed  CAS  Google Scholar 

  32. Khaliq, A., C. Dunk, J. Jiang, M. Shams, X. Li, C. Acevedo, H. Weich, M. Whittle, and A. Ahmed. Hypoxia Down-Regulates Placenta growth factor whereas Fetal Growth Restriction Up-Regulates Placenta growth factor Expresion: Molecular Evidence for “Placental Hyperoxia” in Intrauterine Growth Restriction. Laboratory Investigation 1999.(In Press)

    Google Scholar 

  33. Khong, T.Y., F. De Wolf, W.B. Robertson, and I. Brosens. Inadequate maternal vascular response to placentation in pregnancies complicated by pre-eclampsia and by small-forgestational age infants. Br J Obstet Gynaecol 93: 1049–1059, 1986.

    Article  PubMed  CAS  Google Scholar 

  34. Kingdom, J. Adriana and Luisa Castellucci Award Lecture 1997. Placental pathology in obstetrics: adaptation or failure of the villous tree? Placenta 19: 347–351, 1998.

    Article  Google Scholar 

  35. Kingdom, J.C., S.J. Burrell, and P. Kaufmann. Pathology and clinical implications of abnormal umbilical artery Doppler waveforms. Ultrasound Obstet Gynecol 9: 271–286, 1997.

    Article  PubMed  CAS  Google Scholar 

  36. Kingdom, J.C. and P. Kaufmann. Oxygen and placental villous development: origins of fetal hypoxia. Placenta 18: 613–621, 1997.

    Article  PubMed  CAS  Google Scholar 

  37. Kingdom, J.C., C.H. Rodeck, and P. Kaufmann. Umbilical artery Doppler--more harm than good? Br J Obstet Gynaecol 104: 393–396, 1997.

    Article  PubMed  CAS  Google Scholar 

  38. Krebs, C., L.M. Macara, R. Leiser, A.W. Bowman, I.A. Greer, and J.C. Kingdom. Intrauterine growth restriction with absent end-diastolic flow velocity in the umbilical artery is associated with maldevelopment of the placental terminal villous tree. Am J Obstet Gynecol 175: 1534–1542, 1996.

    Article  PubMed  CAS  Google Scholar 

  39. Kurjak, A. and S. Kupesic. Parallel Doppler assessment of yolk sac and intervillous circulation in normal pregnancy and missed abortion [In Process Citation]. Placenta 19: 619–623,1998.

    Article  PubMed  CAS  Google Scholar 

  40. Kurz, H., J. Wilting, K. Sandau, and B. Christ. Automated evaluation of angiogenic effects mediated by VEGF and P1GF homo-and heterodimers. Microvasc Res 55: 92–102, 1998.

    Article  PubMed  CAS  Google Scholar 

  41. Luckhardt, M., R. Leiser, J. Kingdom, A. Malek, R. Sager, C. Kaisig, and H. Schneider. Effect of physiologic perfusion-fixation on the morphometrically evaluated dimensions of the term placental cotyledon. JSoc Gynecol Investig 3: 166–171, 1996.

    Article  CAS  Google Scholar 

  42. Lyall, F., A. Young, F. Boswell, J.C. Kingdom, and I.A. Greer. Placental expression of vascular endothelial growth factor in placentae from pregnancies complicated by pre-eclampsia and intrauterine growth restriction does not support placental hypoxia at delivery. Placenta 18: 269–276, 1997.

    Article  PubMed  CAS  Google Scholar 

  43. Macara, L., J.C. Kingdom, P. Kaufmann, G. Kohnen, J. Hair, I.A. More, F. Lyall, and I.A. Greer. Structural analysis of placental terminal villi from growth-restricted pregnancies with abnormal umbilical artery Doppler waveforms. Placenta 17: 37–48, 1996.

    Article  PubMed  CAS  Google Scholar 

  44. Maglione, D., V. Guerriero, G. Viglietto, P. Delli-Bovi, and M.G. Persico. Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor. Proc Natl Acad Sci USA 88: 9267–9271, 1991.

    Article  PubMed  CAS  Google Scholar 

  45. Mason, G.C., R.J. Lilford, J. Porter, E. Nelson, and S. Tyrell. Randomised comparison of routine versus highly selective use of Doppler ultrasound in low risk pregnancies. Br J Obstet Gynaecol 100: 130–133, 1993.

    Article  PubMed  CAS  Google Scholar 

  46. Mayhew, T.M., M.R. Jackson, and P.A. Boyd. Changes in oxygen diffusive conductances of human placentae during gestation (10–41 weeks) are commensurate with the gain in fetal weight. Placenta 14: 51–61, 1993.

    Article  PubMed  CAS  Google Scholar 

  47. Morrow, R.J., S.L. Adamson, S.B. Bull, and J.W. Ritchie. Effect of placental embolization on the umbilical arterial velocity waveform in fetal sheep. Am J Obstet Gynecol 161: 1055–1060,1989.

    PubMed  CAS  Google Scholar 

  48. Nylund, L., N.O. Lunell, R. Lewander, and B. Sarby. Uteroplacental blood flow index in intrauterine growth retardation of fetal or maternal origin. Br J Obstet Gynaecol 90: 16–20, 1983.

    Article  PubMed  CAS  Google Scholar 

  49. Ochi, H., K. Matsubara, Y. Kusanagi, H. Taniguchi, and M. Ito. Significance of a diastolic notch in the uterine artery flow velocity waveform induced by uterine embolisation in the pregnant ewe. Br J Obstet Gynaecol 105: 1118–1121, 1998.

    Article  PubMed  CAS  Google Scholar 

  50. Olofsson, P., R.N. Laurini, and K. Marsal. A high uterine artery pulsatility index reflects a defective development of placental bed spiral arteries in pregnancies complicated by hypertension and fetal growth retardation. Eur J Obstet Gynecol Reprod Biol 49: 161–168, 1993.

    Article  PubMed  CAS  Google Scholar 

  51. Ozaki, H., A.Y. Yu, N. Della, K. Ozaki, J.D. Luna, H. Yamada, S.F. Hackett, N. Okamoto, D.J. Zack, G.L. Semenza, and P.A. Campochiaro. Hypoxia inducible factor-1 alpha is increased in ischemic retina: temporal and spatial correlation with VEGF expression. Invest Ophthalmol Vis Sci 40: 182–189, 1999.

    PubMed  CAS  Google Scholar 

  52. Pardi, G., I. Cetin, A.M. Marconi, P. Bozzetti, M. Buscaglia, E.L. Makowski, and F.C. Battaglia. Venous drainage of the human uterus: respiratory gas studies in normal and fetal growth-retarded pregnancies. Am J Obstet Gynecol 166: 699–706, 1992.

    PubMed  CAS  Google Scholar 

  53. Pardi, G., I. Cetin, A.M. Marconi, A. Lanfranchi, P. Bozzetti, E. Ferrazzi, M. Buscaglia, and F.C. Battaglia. Diagnostic value of blood sampling in fetuses with growth retardation [see comments]. N Engl J Med 328: 692–696, 1993.

    Article  PubMed  CAS  Google Scholar 

  54. Poston, L. Nitrovasodilators--will they be useful in lowering uterine artery resistance in pre-eclampsia and intrauterine growth restriction? [comment]. Ultrasound Obstet Gynecol 11:92–93, 1998.

    Article  PubMed  CAS  Google Scholar 

  55. Proud, J. and A.M. Grant. Third trimester placental grading by ultrasonography as a test of fetal wellbeing. Br Med J (Clin Res Ed) 294: 1641–1644, 1987.

    Article  CAS  Google Scholar 

  56. Riley, P., L. Anson-Cartwright, and J.C. Cross. The Handl bHLH transcription factor is essential for placentation and cardiac morphogenesis. Nat Genet 18: 271–275, 1998.

    Article  PubMed  CAS  Google Scholar 

  57. Risau, W. Mechanisms of angiogenesis. Nature 386: 671–674, 1999.

    Google Scholar 

  58. Rodesch, F., P. Simon, C. Donner, and E. Jauniaux. Oxygen measurements in endometrial and trophoblastic tissues during early pregnancy. Obstet Gynecol 80: 283–285, 1992.

    PubMed  CAS  Google Scholar 

  59. Seligman, S.P., T. Nishiwaki, S.S. Kadner, J. Dancis, and T.H. Finlay. Hypoxia stimulates ecNOS mRNA expression by differentiated human trophoblasts. Ann N YAcad Sci 828: 180–187, 1997.

    Article  CAS  Google Scholar 

  60. Taylor, C.M., H. Stevens, F.W. Anthony, and T. Wheeler. Influence of hypoxia on vascular endothelial growth factor and chorionic gonadotrophin production in the trophoblast-derived cell lines: JEG, JAr and Be Wo. Placenta 18: 451–458, 1997.

    Article  PubMed  CAS  Google Scholar 

  61. Valensise, H. Uterine artery Doppler velocimetry as a screening test: where we are and where we go [editorial]. Ultrasound Obstet Gynecol 12: 81–83, 1998.

    Article  PubMed  CAS  Google Scholar 

  62. Ziche, M., D. Maglione, D. Ribatti, L. Morbidelli, C.T. Lago, M. Battisti, I. Paoletti, A. Barra, M. Tucci, G. Parise, V. Vincenti, H.J. Granger, G. Viglietto, and M.G. Persico. Placenta growth factor-1 is chemotactic, mitogenic, and angiogenic. Lab Invest 76: 517–531, 1997.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics & Gynecology, University of Toronto and Maternal-Fetal Medicine Division, Suite 775B Mount Sinai Hospital, 600 University Avenue, Toronto, M5G 1X5, Ontario, Canada

    John C. P. Kingdom & Peter Kaufmann

  2. Department of Anatomy, University of Technology, Aachen, Germany

    John C. P. Kingdom & Peter Kaufmann

Authors
  1. John C. P. Kingdom
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter Kaufmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Life Sciences, New Mexico Highlands University, Las Vegas, New Mexico, USA

    Robert C. Roach

  2. Department of Medicine, University of California San Diego, La Jolla, California, USA

    Peter D. Wagner

  3. St. Mary’s Hospital and Medical Center, University of Washington School of Medicine and Emergency Department, Grand Junction, Colorado, USA

    Peter H. Hackett

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Science+Business Media New York

About this chapter

Cite this chapter

Kingdom, J.C.P., Kaufmann, P. (1999). Oxygen and Placental Vascular Development. In: Roach, R.C., Wagner, P.D., Hackett, P.H. (eds) Hypoxia. Advances in Experimental Medicine and Biology, vol 474. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4711-2_20

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-4711-2_20

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7134-2

  • Online ISBN: 978-1-4615-4711-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation