Advertisement

Placental Vascular Morphogenesis: Introduction and Overview

  • D. Stephen Charnock-Jones
  • Stephen K. Smith
Part of the Cardiovascular Molecular Morphogenesis book series (CARDMM)

Abstract

While it is self-evident that the placenta is essential for the mammalian reproductive process, historically its role has been confused. The precise architectural arrangement of the blood vessels has been a matter of dispute, and this in part can be explained by the diversity of structures observed in common domestic, laboratory, and wild species (for a review of this subject area, see Kaufmann and Burton, 1994). However, by the beginning of the last century it had been established that the placenta served as an organ for fetal nutrition, respiration, and as an endocrine organ. All of the different placental types show specialized adaptations to facilitate exchange between the fetal and maternal circulatory systems. Both the human and murine placentae are of the hemochorial type, and although there are marked differences between them, knockout and transgenic studies in the mouse have been extremely informative. It is a reasonable assumption that the requirements for exchange play the most significant role in determining placental morphology, and therefore the adaptations of the fetal vasculature to facilitate this process are fundamental. In a range of species as gestation advances and fetal demand increases, the capacity of the placenta for exchange increases. In the human, there is a continual elaboration of the principal functional units of the placenta, the terminal villi, and a progressive reduction in the mean thickness of the villous membrane separating the two circulations. These changes, and the changes seen in other species, are dependent on continued angiogenesis, and therefore placental angiogenesis is central for the success of pregnancy.

Keywords

Vascular Endothelial Growth Factor Vascular Endothelial Growth Factor Receptor Human Placenta Trophoblast Cell Extravillous Trophoblast 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ahmed, A., Dunk, C, Ahmad, S., and Khaliq, A. 2000. Regulation of placental vascular endothelial growth factor (VEGF) and placenta growth factor (P1GF) and soluble Flt-1 by oxygen—a review.Placenta21(suppl A):S16–24.PubMedCrossRefGoogle Scholar
  2. Ahmed, A., Dunk, C., Kniss, D., and Wilkes, M. 1997. 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.PubMedGoogle Scholar
  3. Ali, K. Z. M., Burton, G. J., Morad, N., and Ali, M. E. 1996. Does hypercapillarization influence the branching pattern of terminal villi in the human placenta at high altitude?Placenta17:677–682.PubMedCrossRefGoogle Scholar
  4. Alon, T., Hemo, I., Itin, A., Pe’er, J., Stone, J., and Keshet, E. 1995. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity.Nat. Med.1:1024–1028.PubMedCrossRefGoogle Scholar
  5. Athanassiades, A., and Lala, P. K. 1998. Role of placenta growth factor (PIGF) in human extravillous trophoblast proliferation, migration and invasiveness.Placenta19:465–473.PubMedCrossRefGoogle Scholar
  6. Benjamin, L. E., Hemo, I., and Keshet, E. 1998. A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF.Development125:1591–1598.PubMedGoogle Scholar
  7. Benjamin, L. E., and Keshet, E. 1997. Conditional switching of vascular endothelial growth factor (VEGF) expression in tumors: induction of endothelial cell shedding and regression of hemangioblastoma-like vessels by VEGF withdrawal.Proc. Natl. Acad. Sci. USA94:8761–8766.PubMedCrossRefGoogle Scholar
  8. Boocock, C. A., Charnock-Jones, D. S., Sharkey, A. M., McLaren, J., Barker, P. J., Wright, K. A., Twentyman, P. R., and Smith, S. K. 1995. Expression of vascular endothelial growth factor and its receptors flt and KDR in ovarian carcinoma.J. Natl. Cancer Inst.87:506–516.PubMedCrossRefGoogle Scholar
  9. Burton, G. J., Jauniaux, E., and Watson, A. L. 1999. Maternal arterial connections to the placental intervillous space during the first trimester of human pregnancy: the Boyd collection revisited. Am.J. Obstet. Gynecol.181:718–724.PubMedCrossRefGoogle Scholar
  10. Burton, G. J., Reshetnikova, O. S., Milovanov, A. P., and Teleshova, O. V. 1996. Stereological evaluation of vascular adaptations in human placental villi to differing forms of hypoxic stress.Placenta17:49–55.PubMedCrossRefGoogle Scholar
  11. Cao, Y., Chen, H., Zhou, L., Chiang, M. K., Anand-Apte, B., Weatherbee, J. A., Wang, Y., Fang, F., Flanagan, J. G., and Tsang, M.-S. 1996. Heterodimers of placenta growth factor/vascular endothelial growth factor: Endothelial activity, tumor cell expression, and high affinity binding to Flk-1/KDR.J. Biol. Chem.271:3154–3162.PubMedCrossRefGoogle Scholar
  12. Carmeliet, P., Ferreira, V., Breier, G., Pollefeyt, S., Kieckens, L., Gertenstein, M., Fahrig, M., Vandenhoeck, A., Harpal, K., Eberhardt, C., Decleucq, C., Pawling, J., Moons, L., Collen, D., Risau, W., and Nagy, A. 1996. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele.Nature380:435–439.PubMedCrossRefGoogle Scholar
  13. Charnock-Jones, D. S., Sharkey, A. M., Boocock, C. A., Ahmed, A., Plevin, R., Ferrara, N., and Smith, S. K. 1994. Vascular endothelial growth factor receptor localization and activation in human trophoblast and choriocarcinoma cells.Biol. Reprod.51:524–530.PubMedCrossRefGoogle Scholar
  14. Charnock-Jones, D. S., Sharkey, A. M., Rajput-Williams, J., Burch, D., Schofield, J. P., Fountain, S. A., Boocock, C. A., and Smith, S. K. 1993. Identification and localization of alternately spliced mRNAs for vascular endothelial growth factor in human uterus and estrogen regulation in endometrial carcinoma cell lines.Biol. Reprod.48:1120–1128.PubMedCrossRefGoogle Scholar
  15. Clark, D. E., Smith, S. K., He, Y., Day, K. A., Licence, D. R., Corps, A. C., Lammoglia, R., and Charnock-Jones, D. S. 1998a. A vascular endothelial growth factor antagonist is produced by the human placenta and released into the maternal circulation.Biol. Reprod.59:1540–1548.CrossRefGoogle Scholar
  16. Clark, D. E., Smith, S. K., Licence, D., Evans, A. L., and Charnock-Jones, D. S. 1998b. 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.CrossRefGoogle Scholar
  17. Clark, D. E., Smith, S. K., Sharkey, A. M., Sowter, H. M., and Charnock-Jones, D. S. 1996. Hepatocyte growth factor/scatter factor and its receptor c-met: localisation and expression in the human placenta throughout pregnancy.J. Endocrinol.151:459–467.PubMedCrossRefGoogle Scholar
  18. Davis, S., Aldrich, T. H., Jones, P. F., Acheson, A., Compston, D. L., Jain, V., Ryan, T. E., Bruno, J., Radziejewski, C., Maisonpierre, P. C., and Yancopoulos, G. D. 1996. Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning.Cell87:1161–1169.PubMedCrossRefGoogle Scholar
  19. Davis-Smyth, T., Chen, H., Park, J., Presta, L. G., and Ferrara, N. 1996. The second immunoglobulin-like domain of the VEGF tyrosine kinase receptor Flt-1 determines ligand binding and may initiate a signal transduction cascade.EMBO J.15:4919–4927.PubMedGoogle Scholar
  20. Diss, E. M., Gabbe, S. G., Moore, J. W., and Kniss, D. A. 1992. Study of thromboxane and prostacyclin metabolism in an in vitro model of first-trimester human trophoblast.Am. J. Obstet. Gynecol.167:1046–1052.PubMedGoogle Scholar
  21. Ferrara, N., Carver-Moore, K., Chen, H., Dowd, M., Lu, L., O’Shea, H. S., Powell-Braxton, L., Hillan, K. J., and Moore, M. W. 1996. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene.Nature380:439–442.PubMedCrossRefGoogle Scholar
  22. Ferrara, N., Chen, H., Davis-Smith, T., Gerber, H. P., Nguyen, T. N., Peers, D., Chisholm, V., Hillan, K. J., and Schwall, R. H. 1998. Vascular endothelial growth factor is essential for corpus luteum angiogenesis.Nat. Med.4:336–340.PubMedCrossRefGoogle Scholar
  23. Ferrara, N., and Davis-Smyth, T. 1997. The biology of vascular endothelial growth factor.Endocr. Rev.18:4–25.PubMedCrossRefGoogle Scholar
  24. Ferrara, N., Houck, K., Jakeman, L., and Leung, D. W. 1992. Molecular and biological properties of the vascular endothelial growth factor family of proteins.Endocr. Rev.13:18–32.PubMedGoogle Scholar
  25. Fong, G. H., Rossant, J., Gertsenstein, M., and Breitman, M. L. 1995. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium.Nature376:66–70.PubMedCrossRefGoogle Scholar
  26. Fong, G. H., Zhang, L., Bryce, D. M., and Peng, J. 1999. Increased hemangioblast commitment, not vascular disorganization, is the primary defect in flt-1 knock-out mice.Development126:3015–3025.PubMedGoogle Scholar
  27. Hanahan, D. 1997. Signaling vascular morphogenesis and maintenance.Science277:48–50.PubMedCrossRefGoogle Scholar
  28. Hanahan, D., and Folkman, J. 1996. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis.Cell86:353–364.PubMedCrossRefGoogle Scholar
  29. He, Y., Smith, S. K., Day, K. A., Clark, D. E., Licence, D. R., and Charnock-Jones, D. S. 1999. Alternative splicing of vascular endothelial growth factor (VEGF)-R1 (FLT-1) premRNA is important for the regulation of VEGF activity.Mol. Endocrinol.13:537–545.PubMedCrossRefGoogle Scholar
  30. Hiratsuka, S., Minowa, O., Kuno, J., Noda, T., and Shibuya, M. 1998. Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice.Proc. Natl. Acad. Sci. USA95:9349–9354.PubMedCrossRefGoogle Scholar
  31. Houck, K. A., Leung, D. W., Rowland, A. M., Winer, J., and Ferrara, N. 1992. Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms.J. Biol. Chem.267:26031–26037.PubMedGoogle Scholar
  32. Hustin, J., and Schaaps, J. P. 1987. Echographic [corrected] and anatomic studies of the maternotrophoblastic border during the first trimester of pregnancy.Am. J. Obstet. Gynecol.157:162–168.PubMedGoogle Scholar
  33. Jauniaux, E., Zaidi, J., Jurkovic, D., Campbell, S., and Hustin, J. 1994. Comparison of colour Doppler features and pathological findings in complicated early pregnancy.Hum. Reprod.9:2432–2437.PubMedGoogle Scholar
  34. Kaufmann, P., and Burton, G. J. 1994. Anatomy and genesis of the placenta. In: Knobil, E., and Neill, J. D., eds.The Physiology of Reproduction.Raven Press, New York, pp. 441–484.Google Scholar
  35. Kendall, R. L., and Thomas, K. A. 1993. Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor.Proc. Natl. Acad. Sci. USA90:10705–10709.PubMedCrossRefGoogle Scholar
  36. Kendall, R. L., Wang, G., and Thomas, K. A. 1996. Identification of a natural soluble form of the vascular endothelial growth factor receptor, FLT-1, and its heterodimerization with KDR.Biochem. Biophys. Res. Commun.226:324–328.PubMedCrossRefGoogle Scholar
  37. Keyt, B. A., Berleau, L. T., Nguyen, H. V., Chen, H., Heinsohn, H., Vandlen, R., and Ferrara, N. 1996. The carboxyl-terminal domain (111–165) of vascular endothelial growth factor is critical for its mitogenic potency.J. Biol. Chem.271:7788–7795.PubMedCrossRefGoogle Scholar
  38. Kim, K. J., Li, B., Winer, J., Armanini, M., Gillett, N., Phillips, H. S., and Ferrara, N. 1993. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo.Nature362:841–844.PubMedCrossRefGoogle Scholar
  39. King, A., Thomas, L., and Bischof, P. 2000. Cell culture models of trophoblast II: trophoblast cell lines-a workshop report.Placenta21(suppl A):5113-S119.Google Scholar
  40. Kong, H. L., Hecht, D., Song, W., Kovesdi, I., Hackett, N. R., Yayon, A., and Crystal, R. G. 1998. Regional suppression of tumor growth by in vivo transfer of a cDNA encoding a secreted form of the extracellular domain of the flt-1 vascular endothelial growth factor receptor.Hum. Gene Ther.9:823–833.PubMedCrossRefGoogle Scholar
  41. Levy, A. P., Levy, N. S., and Goldberg, M. A. 1996. Post-transcriptional regulation of vascular endothelial growth factor by hypoxia.J. Biol. Chem.271:2746–2753.PubMedCrossRefGoogle Scholar
  42. Maglione, D., Guerriero, V., Viglietto, G., Delli-Bovi, P., and Persico, M. G. 1991. Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor.Proc. Natl. Acad. Sci. USA88:9267–9271.PubMedCrossRefGoogle Scholar
  43. Maisonpierre, P. C., Suri, C., Jones, P. F., Bartunkova, S., Wiegand, S. J., Radziejewski, C., Compton, D., McClain, J., Aldrich, T. H., Papadopoulos, N., Daly, T. J., Davis, S., Sato, T. N., and Yancopoulos, G. D. 1997. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis.Science277:55–60.PubMedCrossRefGoogle Scholar
  44. Millauer, B., Shawver, L. K., Plate, K. H., Risau, W., and Ullrich, A. 1994. Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant.Nature367:576–578.PubMedCrossRefGoogle Scholar
  45. Murohara, T., Horowitz, J. R., Silver, M., Tsurumi, Y., Chen, D., Sullivan, A., and Isner, J. M. 1998. Vascular endothelial growth factor/vascular permeability factor enhances vascular permeability via nitric oxide and prostacyclin.Circulation97:99–107.PubMedCrossRefGoogle Scholar
  46. Papapetropoulos, A., Garcia-Cardena, G., Madri, J. A., and Sessa, W. C. 1997. Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells.J. Clin. Invest.100:3131–3139.PubMedCrossRefGoogle Scholar
  47. Park, J. E., Chen, H. H., Winer, J., Houck, K. A., and Ferrara, N. 1994. Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR.J. Biol. Chem.269:25646–25654.PubMedGoogle Scholar
  48. Pepper, M. S., Ferrara, N., Orci, L., and Montesano, R. 1991. Vascular endothelial growth factor (VEGF) induces plasminogen activators and plasminogen activator inhibitor-1 in microvascular endothelial cells.Biochem. Biophys. Res. Commun.181:902–906.PubMedCrossRefGoogle Scholar
  49. Pepper, M. S., and Montesano, R. 1990. Proteolytic balance and capillary morphogenesis.Cell. Differ. Dev.32:319–328.PubMedCrossRefGoogle Scholar
  50. Pepper, M. S., Sappino, A. P., Montesano, R., Orci, L., and Vassalli, J. D. 1992. Plasminogen activator inhibitor-1 is induced in migrating endothelial cells.J. Cell. Physiol.153:129–139.PubMedCrossRefGoogle Scholar
  51. Roberts, J. M. 1998. Endothelial dysfunction in preeclampsia.Semin. Reprod. Endocrinol.16:5–15.PubMedCrossRefGoogle Scholar
  52. Robertson, W. B., Brosens, I., and Dixon, G. 1976. Maternal uterine vascular lesions in the hypertensive complications of pregnancy.Perspect. Nephrol. Hypertens.5:115–127.PubMedGoogle Scholar
  53. Sato, Y. 1996. Current state of anti-angiogenic therapy.Biotherapy10:972–978.Google Scholar
  54. Schmidt, C., Bladt, F., Goedecke, S., Brinkmann, V., Zschiesche, W., Sharpe, M., Gherardi, E., and Birchmeier, C. 1995. Scatter factor/hepatocyte growth factor is essential for liver development.Nature373:699–702.PubMedCrossRefGoogle Scholar
  55. Shalaby, F., Rossant, J., Yamaguchi, T. P., Gertsenstein, M., Wu, X. F., Breitman, M. L., and Schuh, A. C. 1995. Failure of blood-island formation and vasculogenesis in Flk-1 deficient mice.Nature376:62–66.PubMedCrossRefGoogle Scholar
  56. Sharkey, A. M., Charnock-Jones, D. S., Boocock, C. A., Brown, K. D., and Smith, S. K. 1993. Expression of mRNA for vascular endothelial growth factor in human placenta.J. Reprod. Fertil.99:609–615.PubMedCrossRefGoogle Scholar
  57. Shibuya, M., Yamaguchi, S., Yamane, A., Ikeda, T., Tojo, A., Matsushime, H., and Sato, M. 1990. Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family.Oncogene5:519–524.PubMedGoogle Scholar
  58. Shiraishi, S., Nakagawa, K., Kinukawa, N., Nakano, H., and Sueishi, K. 1996. Immunohistochemical localization of vascular endothelial growth factor in the human placenta.Placenta17:111–121.PubMedCrossRefGoogle Scholar
  59. Takakura, N., Huang, X. L., Naruse, T., Hamaguchi, I., Dumont, D. J., Yancopoulos, G. D., and Suda, T. 1998. Critical role of the TIE2 endothelial cell receptor in the development of definitive hematopoiesis.Immunity9:677–686.PubMedCrossRefGoogle Scholar
  60. Terman, B. I., Carrion, M. E., Kovacs, E., Rasmussen, B. A., Eddy, R. L., and Shows, T. B. 1991. Identification of a new endothelial cell growth factor receptor tyrosine kinase.Oncogene6:1677–1683.PubMedGoogle Scholar
  61. Torry, D. S., Wang, H. S., Wang, T. H., Caudle, M. R., and Torry, R. J. 1999. Preeclampsia is associated with reduced serum levels of placenta growth factor. Am.J. Obstet. Gynecol.179:1539–1544.CrossRefGoogle Scholar
  62. Uehara, Y., Minowa, O., Mori, C., Shiota, K., Kuno, J., Noda, T., and Kitamura, N. 1995. Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor.Nature373:702–705.PubMedCrossRefGoogle Scholar
  63. Vuckoviv, M., Ponting, J., Terman, B. I., Niketic, V., Seif, M. W., and Kumar, S. 1996. Expression of the vascular endothelial growth factor receptor, KDR, in human placenta.J. Anat.188:361–366.Google Scholar
  64. Vuorela, P., Hatva, E., Lymboussaki, A., Kaipainen, A., Joukov, V., Persico, M. G., Alitalo, K., and Halmesmaki, E. 1997. Expression of vascular endothelial growth factor and placenta growth factor in human placenta.Biol. Reprod.56:489–494.PubMedCrossRefGoogle Scholar
  65. Wheeler, T., Elcock, C. L., and Anthony, F. W. 1995. Angiogenesis and the placental environment.Placenta16:289–296.PubMedCrossRefGoogle Scholar
  66. Ziche, M., Maglione, D., Ribatti, D., Morbidelli, L., Lago, C. T., Battisti, M., Paoletti, I., Barra, A., Tucci, M., Parise, G., Vincenti, V., Granger, H. J., Viglietto, G., Persico, M. G. 1997. Placenta growth factor-1 is chemotactic, mitogenic, and angiogenic.Lab Invest76:517–531PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • D. Stephen Charnock-Jones
  • Stephen K. Smith

There are no affiliations available

Personalised recommendations