Biochemical and Immunological Aspects of the Human Trophoblast Cell Surface

A Review
  • Paul D. Webb
  • Nicholas Hole
  • P. Jeremy McLaughlin
  • Peter L. Stern
  • Peter M. Johnson
Part of the Trophoblast Research book series (TR)


Following blastocyst implantation, the outer layer of human trophoblast rapidly proliferates and several anatomically distinct populations of trophoblast develop in the placenta and extraembryonic membranes as gestation progresses (Hertig et al., 1954; Boyd and Hamilton, 1970; Bulmer and Johnson, 1985). The major trophoblast population covers chorionic villi (or conversely lines intervillous spaces) and is therefore in intimate contact with maternal blood. This villous trophoblast layer is organized into an inner cytotrophoblast and an outer syncytiotrophoblast layer with numerous microvilli on the maternal-facing surface. Also of relevance to this review is extravillous cytotrophoblast which proliferates into maternal uterine tissue from the implantation site. Since high purity preparations of syncytiotrophoblast surface microvillous plasma membrance (StMPM) can be readily obtained from term placentae (Smith et al., 1974; Ogbimi et al., 1979), the majority of biochemical and immunological studies have centered on syncytiotrophoblast.


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  1. Adamson, E.D., Meek, J., and Edwards, S.A. (1985) Product of the cellular oncogene, c-fos, observed in mouse and human tissues using an antibody to a synthetic peptide. EMBO. J. 4, 941–947.PubMedGoogle Scholar
  2. Anderson, D.J. and Berkowitz, R.S. (1985) Gamma-interferon enhances expression of class I MHC antigens in the weakly HLA-positive human choriocarcinoma cell line BeWo but does not induce MHC expression in the HLA-negative choriocarcinoma cell line JAr. J. Immunol. 135, 2498–2501.PubMedGoogle Scholar
  3. Andrews, P.W., Damjanov, I., Simon, D., Banting, G.S., Carliu, C., Dracopoli, N.C., and Fogh, J. (1984) Pluripotent embryonal carcinoma clones derived from the human teratocarcinoma cell line Tera2. Lab. Invest. 50, 147–162.PubMedGoogle Scholar
  4. Aspinall, R. and Stern, P.L. (1985) Analysis of the xenogeneic T-cell response to murine H-2 negative embryonal carcinoma cells. Immunol. 54, 549–557.Google Scholar
  5. Avruch, J., Nemenoff, R.A., Blackshear, P.J., Pierce, M.W., and Osathanondh, R. (1982) Insulin-stimulated tyrosine phosphorylation of the insulin receptor in detergent extracts of human placental membranes. J. Biol. Chem. 257, 1516215166.Google Scholar
  6. Bell, S.M. and Stern, P.L. (1985) Rat natural killer cells and cytotoxic T cell lysis of H- 2 negative murine embryonal carcinomal cells. Eur. J. Immunol. 15, 59–65.PubMedCrossRefGoogle Scholar
  7. Berridge, M.J. (1984) Inositol trisphosphate and diacylglycerol as second messengers. Biochem. J. 220, 345–360.PubMedGoogle Scholar
  8. Boyd, J.D. and Hamilton, W.J. (1970) The Human Placenta. W. Heffer and Sons Ltd., Cambridge.Google Scholar
  9. Bulmer, J.N., Billington, W.D., and Johnson, P.M. (1984) Immunohistologic identification of trophoblast populations in early human pregnancy with the use of monoclonal antibodies. Am. J. Obstet. Gynecol. 148, 19–26.PubMedCrossRefGoogle Scholar
  10. Bulmer, J.N. and Johnson, P.M. (1985) Antigen expression by trophoblast populations in the human placenta and their possible immunobiological relevance. Placenta 6, 127–140.PubMedCrossRefGoogle Scholar
  11. Carson, S.A., Chase, R., Wep, E., Scommegna, A., and Benveniste, R. (1983) Ontogenesis and characteristics of epidermal growth factor receptors in human placenta. Am. J. Obstet. Gynecol. 147, 932–939.PubMedGoogle Scholar
  12. Cheng, H.M. and Johnson, P.M. (1985) A description of human placental syncytiotrophoblast membrane glycosphinoglipids. Placenta 6, 229–238.PubMedCrossRefGoogle Scholar
  13. Cohen, P. (1982) The role of protein phosphorylation in neural and hormonal control of cellular activity. Nature 296, 613–620.PubMedCrossRefGoogle Scholar
  14. Covone, A.E., Mutton, D., Johnson, P.M., and Adinolfi, M. (1984) Trophoblast cells in peripheral blood from pregnant women. Lancet ii, 841–843.Google Scholar
  15. Critchley, M., Brownless, S., Patten, M., McLaughlin, P.J., Tromans, P.M., and Johnson, P.M. (1986) Radionuclide imaging of epithelial ovarian tumours with ’231-labelled monoclonal antibody (H317). Clin. Radiol. 37, 107–112.PubMedCrossRefGoogle Scholar
  16. Earl, U., Wells, M., and Bulmer, J.N. (1985) The expression of major histocompatibility complex antigens by trophoblast in ectopic tubal pregnancy. J. Reprod. Immunol. 8, 13–24.PubMedCrossRefGoogle Scholar
  17. Ebina, Y., Ellis, L., Jarnagin, K., Edery, M., Graf, L., Clauser, E., Ou, J.H., Masiarz, F., Kan, Y.W., Goldfine, I.D., Roth, R.A., and Rutter, W.J. (1985) The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling. Cell 40, 747–758.PubMedCrossRefGoogle Scholar
  18. Epenetos, A.A., Munro, A.J., Tucker, D.F., Gregory, W., Duncan, W., MacDougall, R.H., Faux, M., Travers, P., and Bodmer, W.F. (1985a) Monoclonal antibody assay of serum placental alkaline phosphatase in the monitoring of testicular tumours. Br. J. Can. 51, 641–644.CrossRefGoogle Scholar
  19. Epenetos, A.A., Snook, D., Hooker, G., Begent, R., Durbin, H., Oliver, R.T.D., Bodmer, W.F., and Lavender, J.P. (1985b) Indium-111 labelled monoclonal antibody to placental aklaline phosphatase in the detection of neoplasms of testis, ovary, and cervix. Lancet ii, 350–353.Google Scholar
  20. Ezra, E., Blacher, R., and Udenfriend, S. (1983) Purification and partial sequencing of human placental alkaline phosphatase. Biochem. Biophys. Res. Commun. 116, 1076–1083.PubMedCrossRefGoogle Scholar
  21. Fishman, W.H. (1974) Perspectives on alkaline phosphatase isoenzymes. Am. J. Med. 56, 617–650.PubMedCrossRefGoogle Scholar
  22. Goustin, A.T., Betsholtz, C., Pfeifer-Ohlsson, S., Persson, H., Rydnert, J., Bywater, M., Homgren, G., Heldin, C.-H., Westermark, B., and Ohlsson, R. (1985) Co-expression of the sis and myc proto-oncogenes in developing human placenta suggests autocrine control of trophoblast growth. Cell 41, 301–312.PubMedCrossRefGoogle Scholar
  23. Hakomori, S.-I. (1985) Abberrant glycosylation in cancer cell membranes as focused on glycolipids. Overview and perspectives. Cancer Res. 45, 2405–2414.PubMedGoogle Scholar
  24. Hertig, A.T., Rock, J., and Adams, E.C. (1956) A description of 34 human ova within the first 17 days of development. Am. J. Anat. 98, 435–494.PubMedCrossRefGoogle Scholar
  25. Hsi, B.-L., Yeh, C.J.-G., and Faulk, W.P. (1984) Class I antigens of the major histocompatibility complex on cytotrophoblast of the human chorion laeve. Immunol. 52, 621–629.Google Scholar
  26. Hunter, T. (1984) The epidermal growth factor receptor gene and its product. Nature 311, 414–415.PubMedCrossRefGoogle Scholar
  27. Johnson, P.M. (1984) Immunobiology of the human trophoblast. In: Immunological Aspects of Reproduction. in Mammals, (ed.), D.B Crighton, Butterworth Press, London, pp. 109–131.Google Scholar
  28. Johnson, P.M. and Brown, P.J. (1981) Fc y receptors in the human placenta. Placenta 2, 355–370.PubMedCrossRefGoogle Scholar
  29. Johnson, P.M., Brown, P.J., and Faulk, W.P. (1980) Immunobiological aspects of the human placenta. In: Oxford Reviews of Reproductive Biology, vol. 2 (ed.), C.A. Finn, Oxford University Press, Oxford, pp. 1–40.Google Scholar
  30. Kabawat, S.E., Moustafi-Zadeh, M., Driscoll, S.G., and Bhan, A.K. (1985) Implantation site in normal pregnancy: A study with monoclonal antibodies. Am. J. Pathol. 118, 76–84.PubMedGoogle Scholar
  31. Kalter, S.S. (1983) Viral expression in the trophoblast. In: Biology of Trophoblast, (eds.), Y.W. Loke and A. Whyte, Elsevier, Amsterdam, pp. 627–662.Google Scholar
  32. Kawata, M., Parnes, J.R., and Herzenberg, L.A. (1984) Transcriptional control of HLA-A,B,C antigens in human placental cytotrophoblast isolated using trophoblast and H LA-specific monoclonal antibodies and the fluorescence-activated cell sorter. J. Exp. Med. 160, 633–651.PubMedCrossRefGoogle Scholar
  33. Klareskog, L., Forsum, U., and Peterson, P.A. (1980) Hormonal regulation of the expression of la antigens on mammary gland epithelium. Eur. J. Immunol. 10, 958–963.PubMedCrossRefGoogle Scholar
  34. Low, M.G. and Zilversmit, D.B. (1980) Role of phosphatidylinositol in attachment of alkaline phosphatase to membranes. Biochem. 19, 3913–3918.CrossRefGoogle Scholar
  35. McDicken, I.W., McLaughlin, P.J., Tromans, P.M., Luesley, D.M., and Johnson, P.M. (1985) Detection of placental-type alkaline phosphatase in ovarian cancer. Br. J. Cancer 52, 59–64. Google Scholar
  36. McIntyre, J.A. and Faulk, W.P. (1979) Antigens of human trophoblast. J. Exp. Med. 149, 824–833.PubMedCrossRefGoogle Scholar
  37. McIntyre, J.A. and Faulk, W.P. (1982) Allotypic trophoblast-lymphocyte cross reactive (TLX) cell surface antigens. Human Immunol. 4, 27–35.CrossRefGoogle Scholar
  38. McLaughlin, P.J., Cheng, H.M., Slade, M.B., and Johnson, P.M. (1982) Expression on cultured human tumour cells of placental trophoblast membrane antigens and placental alkaline phosphatase defined by monoclonal antibodies. Int. J. Cancer 30, 21–26.PubMedCrossRefGoogle Scholar
  39. McLaughlin, P.J., Travers, P.J., McDicken, I.W., and Johnson, P.M. (1984) Demonstration of placental and placental-like alkaline phosphatases on nonmalignant human extracts using monoclonal antibodies in enzyme immunoassay. Clin. Chim. Acta 137, 341–348.PubMedCrossRefGoogle Scholar
  40. Maeda, S., Yonezawa, K., and Yachi, A. (1985) Serum antibody reacting with placental syncytiotrophoblast in sera of patients with autoimmune diseases–a possible relation to type C RNA retrovirus. Clin. Exp. Immunol. 60, 645–653.PubMedCentralPubMedGoogle Scholar
  41. Magid, M., Nanney, L.B., Stoscheck, C.M., and King, L.E. (1985) Epidermal growth factor binding and receptor distributions in term human placenta. Placenta 6, 519–526.PubMedCrossRefGoogle Scholar
  42. Muller, R., Tremblay, J.M., Adamson, E.D., and Verma, I.M. (1983) Tissue and cell type-specific expression of two human c-onc genes. Nature 304, 454–456.PubMedCrossRefGoogle Scholar
  43. Nelson, D.M., Enders, A.C., and King, B.F. (1978) Cytological events involved in glycoprotein synthesis in cellular and syncytial trophoblast of human placenta. An electron microscope autoradiographic study of [3-H] galactose incorporation. J. Cell. Biol. 76, 418–429.PubMedCrossRefGoogle Scholar
  44. Nishizuka, Y. (1984) The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature 308, 693–698.PubMedCrossRefGoogle Scholar
  45. Ogbimi, A.O. and Johnson, P.M. (1980) Further immunological and chemical characterization of human syncytiotrophoblast microvillous plasma membrane-associated components. J. Reprod. Immunol. 2, 99–108.CrossRefGoogle Scholar
  46. Ogbimi, A.O., Johnson, P.M., Brown, P.J., and Fox, H. (1979) Characterisation of the soluble fraction of human syncytiotrophoblast microvillous plasma membrane-associated proteins. J. Reprod. Immunol. 1, 127–140.Google Scholar
  47. Pfeifer-Ohlsson, S., Goustin, A.S., Rydnert, J., Bjersing, L., Wahlstrom, T., Stehlin, D., and Ohlsson, R. (1984) Spatial and temporal pattern of cellular myc oncogene expression in developing human placenta: Implications for embryonic cell proliferation. Cell 38, 585–596.PubMedCrossRefGoogle Scholar
  48. Rao, C.V., Ramani, N., Chegini, N., Stadig, B.K., Carman, F.R., Woost, P.G., Schultz, G.S., and Cook, C.L. (1985) Topography of human placental receptors for epidermal growth factor. J. Biol. Chem. 260, 1705–1710.PubMedGoogle Scholar
  49. Redman, C.W.G., McMichael, A.J., Stirrat, G.M., Sunderland, C.A., and Ting, A. (1984) Class I MHC antigens on extravillous trophoblast. Immunol. 52, 457468.Google Scholar
  50. Renzo, G.C.D., Johnston, J.M., Okazaki, T., Okita, J.R., MacDonald, P.C., and Bleasdale, J.C. (1981) Phosphatidylinositol-specific phospholipase C in fetal membranes and uterine decidua. J. Clin. Invest. 67, 847–856.PubMedCentralPubMedCrossRefGoogle Scholar
  51. Rettig, W.J., Cordon-Carlo, C., Koulos, J.P., Lewis, J.L., Oettgen, H.F., and Old, L.J. (1985) Cell surface antigens of human trophoblast and choriocarcinoma defined by monoclonal antibodies. Int. J. Cancer 35, 469–475.PubMedCrossRefGoogle Scholar
  52. Richards, R.C., Beardmore, J.M., Brown, P.J., Molloy, C.M., and Johnson, P.M. (1983) Epidermal growth factor receptors on isolated human placental syncytiotrophoblast plasma membrane. Placenta 4, 133–138.PubMedCrossRefGoogle Scholar
  53. Risk, J.M. and Johnson, P.M. (1985) Antigen expression by human trophoblast and tumor cells: models for gene regulation? In: Contributions in Gynecology and Obstetrics,S. Karger, AG, Basel, in press.Google Scholar
  54. Rosa, F. and Fellous, M. (1984) The effect of gamma-interferon on MHC antigens. Immunol. Today 5, 261–262.CrossRefGoogle Scholar
  55. Sakiyama, T., Robinson, J.C., and Chou, J.Y. (1979) Characterization of alkaline phosphatases from first-trimester human placentae. J. Biol. Chem. 254, 935938.Google Scholar
  56. Scott, I.V., Bardsley, W.G., Gregory, H., and Tindall, V.R. (1979) Human placental diamine oxidase concentration and urogastrone: a possible role in polyamine metabolism and fetal growth. In: Proceedings of the 8th International Google Scholar
  57. Symposium on Clinical Enzymology,(eds.), A. Berlina and L. Galzingera, Piccini Medical Books, Padua and London, pp. 563–578.Google Scholar
  58. Sherr, C.J., Rettenmier, C.W., Sacca, R., Roussel, M.R., Look, A.T., and Stanley, E.R. (1985) The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell 41, 665–676.PubMedCrossRefGoogle Scholar
  59. Shukla, S.D. (1982) Phosphatidylinosiotol specific phospholipase C. Life Sci. 18, 1323–1335.CrossRefGoogle Scholar
  60. Smith, N.C., Brush, M.G., and Luckett, S. (1974) Preparation of human placental villous surface membranes. Nature 252, 302–393.PubMedCrossRefGoogle Scholar
  61. Snyder, D.S., Beller, D.I. and Unanue, E.R. (1982) Prostaglandins modulate macrophage la expression. Nature 299, 163–165.PubMedCrossRefGoogle Scholar
  62. Stern, P.L. (1983) Serological and cell-mediated immune recognition of teratocarcinomas. In: Current Problems in Germ Cell Differentiation, (eds.), A. McLaren and C.C. Wylie, Cambridge University Press, pp. 157–173.Google Scholar
  63. Stern, P.L. (1984) Differentiation antigens of embryonal carcinoma cells and embryos. Brit. Med. Bull. 40, 218–223.PubMedGoogle Scholar
  64. Stern, P.L., Beresford, N., Thompson, S., Johnson, P.M., Webb, P.D. and Mole, N. (1986) Characterization of the human trophoblast-leukocyte antigenic molecules defined in a monoclonal antibody. J. Immunol.,in press.Google Scholar
  65. Strachan, T., Sodoyer, R., Damotte, M., and Jordan, B.R. (1984) Complete nucleotide sequence of a functional class I HLA gene, HLA-A3: Implications for the evolution of HLA genes. EMBO. J. 3, 887–894.PubMedGoogle Scholar
  66. Sunderland, C.A., Redman, C.W.G., and Stirrat, G.M. (1985) Characterization and localization of HLA antigens on hydatidiform mole. Am. J. Obstet. Gynecol. 151, 130–135.PubMedCrossRefGoogle Scholar
  67. Suni, J., Narvaren, A., Wahlstrom, T., Aho, M., Pakkanen, R., Vaheri, A., Copeland, T., Cohen, M., and Oroszlan, S. (1984a) Human placental syncytiotrophoblast Mr 75,000 polypeptide defined by antibodies to a synthetic peptide based on a cloned human endogenous retroviral DNA sequence. Proc. Natl. Acad. Sci., USA,81,.6197–6201.Google Scholar
  68. Suni, J., Narvanen, A., Wahlstrom, T., Lehtovirta, P., and Vaheri, A. (1984b) Monoclonal antibody to human T-cell leukemia virus p19 defines polypeptide antigen in human choriocarcinoma cells and syncytiotrophoblast of first trimester placentas. Int. J. Cancer 33, 293–298.PubMedCrossRefGoogle Scholar
  69. Suni, J., Wahlstrom, T., and Vaheri, A. (1981) Retrovirus p30-related antigen in human syncytiotrophobalst and IgG antibodies in cord sera. Int. J. Cancer 28, 559–566.PubMedCrossRefGoogle Scholar
  70. Swarup, G., Cohen, S., and Garberg, D.L. (1981) Selective dephosphorylation of proteins containing phosphotyrosine by alkaline phosphatase. J. Biol. Chem. 256, 8197–8201.PubMedGoogle Scholar
  71. Thiry, L., Loke, Y.W., Hard, R.C., Sprecher-Goldberger, S., and Buekens, P. (1981) Heterologous antiserum to human syncytiotrophoblast membrane is cytotoxic to retrovirus-producing cells and to some cancer cell lines. Am. J. Reprod. Immunol. 1, 241–245.Google Scholar
  72. Thompson, S., Stern, P.L., Webb, M., Walsh, F.S., Engstrom, W., Evans, E.P., Shi, W.-K., Hopkins, B., and Graham, C.F. (1984) Differentiation of neuron-like cells and other cell types from cloned human teratoma cells cultured in retinoic acid. J. Cell Sci. 72, 37–64.PubMedGoogle Scholar
  73. Truman, P., and Ford, H.C. (1984) The brush border of the human term placenta. Biochim. Biophys. Acta 779, 139–160.Google Scholar
  74. Wahlstrom, T., Nieminen, P., Narvanen, A., Suni, J., Lehtoviria, P., Saskela, A., and Vaheri, A. (1984) Monoclonal antibody defining a human syncytiotrophoblast polypeptide immunologically related to mammalian retrovirus structural protein p30. Placenta 5, 465–474.Google Scholar
  75. Watts, C. (1985) In situ 125I-labelling of endosome proteins with lactoperoxidase conjugates. EMBO. J. 3, 1965–1970.Google Scholar
  76. Webb, P.D., Evans, P.W., Molloy, C.M., and Johnson, P.M. (1985) Biochemical studies of human placental microvillous plasma membrane proteins. Am. J. Reprod. Immunol. Microbiol. 8, 113–119.PubMedGoogle Scholar
  77. Webb, P.D., McLaughlin, P.J., Risk, J.M., and Johnson, P.M. (1986) Isolation of placental-type alkaline phosphatase associated with human syncytiotrophoblast membranes using monoclonal antibodies. Placenta,in press.Google Scholar
  78. Wells, M., Hsi, B.-L., and Faulk, W.P. (1984) The expression of class I antigens of the major histocompatibility complex on the cytotrophoblast shell cells of the placental basal plate. Am. J. Reprod. Immunol. 6, 167–174.PubMedCrossRefGoogle Scholar
  79. Whyte, A. (1983) Biochemistry of the human syncytiotrophoblast plasma membrane. In: Biology of Trophoblast, (eds.), Y.W. Loke and A. Whyte, Elsevier, Amsterdam, pp. 513–529.Google Scholar
  80. Wild, A.E. (1983) Trophoblast cell surface receptors. In: Biology of Trophoblast, (eds.), Y.W. Loke and A. Whyte, Elsevier, Amsterdam, pp. 472–505.Google Scholar
  81. Winoto, A., Steinmetz, M., and Hood, L. (1983) Genetic mapping in the major histocompatbility complex by restriction enzyme polymorphisms. Most mouse class I genes map to the Tla complex. Proc. Natl. Acad. Sci., USA, 80, 3425-3429.Google Scholar

Copyright information

© Springer Science+Business Media New York 1987

Authors and Affiliations

  • Paul D. Webb
    • 1
  • Nicholas Hole
    • 1
  • P. Jeremy McLaughlin
    • 1
  • Peter L. Stern
    • 1
  • Peter M. Johnson
    • 1
  1. 1.Pregnancy Immunology Group Department of ImmunologyUniversity of LiverpoolLiverpoolUK

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