Skip to main content

Advertisement

SpringerLink
Log in

The feto–maternal interface: setting the stage for potential immune interactions

  • Review
  • Published:
Seminars in Immunopathology Aims and scope Submit manuscript

Abstract

Human implantation and placentation comprise the direct contact of fetal with maternal tissues culminating in the erosion of maternal tissues by fetal cells. A complex interplay of maternal and fetal factors is key to maintain pregnancy until delivery. Immunological interactions can be found at different stages, such as blastocyst attachment, trophoblast invasion into maternal tissues, and flow of maternal blood through the placenta. These interactions need tightly controlled mechanisms to avoid rejection of the conceptus. In this study, these sites of interaction are introduced on a morphological level to help immunologists create their hypotheses on how the immunological interactions may work.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Rossant J, Cross JC (2001) Placental development: lessons from mouse mutants. Nat Rev Genet 2:538–548

    Article  PubMed  CAS  Google Scholar 

  2. McLennan JE (1968) Implications of eccentricity of the human umbilical cord. Am J Obstet Gynecol 101:1124–1130

    PubMed  CAS  Google Scholar 

  3. Jauniaux E, Englert Y, Vanesse M, Hidden M, Wilkin P (1990) Pathologic features of placentas from singleton pregnancies obtained by in vitro fertilization and embryo transfer. Obstet Gynecol 76:61–64

    PubMed  CAS  Google Scholar 

  4. Murphy CR (2000) Understanding the apical surface markers of uterine receptivity: pinopods or uterodomes? Hum Reprod 15:2451–2454

    Article  PubMed  CAS  Google Scholar 

  5. Huppertz B, Bartz C, Kokozidou M (2006) Trophoblast fusion: fusogenic proteins, syncytins and ADAMs, and other prerequisites for syncytial fusion. Micron 37:509–517

    PubMed  CAS  Google Scholar 

  6. Aplin JD (2006) Embryo implantation: the molecular mechanism remains elusive. Reprod Biomed Online 13:833–839

    Article  PubMed  CAS  Google Scholar 

  7. Boyd JD, Hamilton WJ (1970) The human placenta. Heffer, Cambridge

    Google Scholar 

  8. Huppertz B, Poliard E, Kadyrov M, Peeters L (2006) Oxygen-dependent invasion of first trimester cytotrophoblasts into amnionic mesenchyme. Placenta 27:A29

    Article  Google Scholar 

  9. Larsen JF (1970) Electron microscopy of nidation in the rabbit and observations on the human trophoblastic invasion. In: Hubinot PO, Leroy CR, Leleux P (eds) Ovoimplantation, human gonadotropin and prolactin. Karger, Basel, pp 38–51

    Google Scholar 

  10. Luckett WP (1978) Origin and differentiation of the yolk sac and extraembryonic mesoderm in presomite human and rhesus monkey embryos. Am J Anat 152:59–97

    Article  PubMed  CAS  Google Scholar 

  11. Moffett A, Loke YW (2004) The immunological paradox of pregnancy: a reappraisal. Placenta 25:1–8

    Article  PubMed  CAS  Google Scholar 

  12. Kaufmann P, Castellucci M (1997) Extravillous trophoblast in the human placenta. A review. Trophoblast Res 10:21–65

    Google Scholar 

  13. Benirschke K, Kaufmann P, Baergen R (2006) Pathology of the human placenta, 5th edn. Springer, Berlin Heidelberg New York

    Google Scholar 

  14. Bulmer JN, Morrison L, Johnson PM (1988) Expression of the proliferation markers Ki67 and transferrin receptor by human trophoblast populations. J Reprod Immunol 14:291–302

    Article  PubMed  CAS  Google Scholar 

  15. Muhlhauser J, Crescimanno C, Kaufmann P, Hofler H, Zaccheo D, Castellucci M (1993) Differentiation and proliferation patterns in human trophoblast revealed by c-erbB-2 oncogene product and EGF-R. J Histochem Cytochem 41:165–173

    PubMed  CAS  Google Scholar 

  16. Kemp B, Kertschanska S, Kadyrov M, Rath W, Kaufmann P, Huppertz B (2002) Invasive depth of extravillous trophoblast correlates with cellular phenotype: a comparison of intra- and extrauterine implantation sites. Histochem Cell Biol 117:401–414

    Article  PubMed  CAS  Google Scholar 

  17. Kosanke G, Kadyrov M, Korr H, Kaufmann P (1998) Maternal anemia results in increased proliferation in human placental villi. Trophoblast Res 11:339–357

    Google Scholar 

  18. Frank HG, Malekzadeh F, Kertschanska S, Crescimanno C, Castellucci M, Lang I, Desoye G, Kaufmann P (1994) Immunohistochemistry of two different types of placental fibrinoid. Acta Anat (Basel) 150:55–68

    CAS  Google Scholar 

  19. Damsky CH, Fitzgerald ML, Fisher SJ (1992) Distribution patterns of extracellular matrix components and adhesion receptors are intricately modulated during first trimester cytotrophoblast differentiation along the invasive pathway, in vivo. J Clin Invest 89:210–222

    PubMed  CAS  Google Scholar 

  20. Damsky CH, Librach C, Lim KH, Fitzgerald ML, McMaster MT, Janatpour M, Zhou Y, Logan SK, Fisher SJ (1994) Integrin switching regulates normal trophoblast invasion. Development 120:3657–3666

    PubMed  CAS  Google Scholar 

  21. Aplin JD (1993) Expression of integrin alpha 6 beta 4 in human trophoblast and its loss from extravillous cells. Placenta 14:203–215

    Article  PubMed  CAS  Google Scholar 

  22. Irving JA, Lala PK (1995) Functional role of cell surface integrins on human trophoblast cell migration: regulation by TGF-beta, IGF-II, and IGFBP-1. Exp Cell Res 217:419–427

    Article  PubMed  CAS  Google Scholar 

  23. Huppertz B, Kertschanska S, Frank HG, Gaus G, Funayama H, Kaufmann P (1996) Extracellular matrix components of the placental extravillous trophoblast: immunocytochemistry and ultrastructural distribution. Histochem Cell Biol 106:291–301

    PubMed  CAS  Google Scholar 

  24. Frank HG, Huppertz B, Kertschanska S, Blanchard D, Roelcke D, Kaufmann P (1995) Anti-adhesive glycosylation of fibronectin-like molecules in human placental matrix-type fibrinoid. Histochem Cell Biol 104:317–329

    Article  PubMed  CAS  Google Scholar 

  25. Huppertz B, Kertschanska S, Demir AY, Frank HG, Kaufmann P (1998) Immunohistochemistry of matrix metalloproteinases (MMP), their substrates, and their inhibitors (TIMP) during trophoblast invasion in the human placenta. Cell Tissue Res 291:133–148

    Article  PubMed  CAS  Google Scholar 

  26. King BF, Blankenship TN (1997) Immunohistochemical localization of fibrillin in developing macaque and term human placentas and fetal membranes. Microsc Res Tech 38:42–51

    Article  PubMed  CAS  Google Scholar 

  27. Feinberg RF, Kliman HJ, Lockwood CJ (1991) Is oncofetal fibronectin a trophoblast glue for human implantation? Am J Pathol 138:537–543

    PubMed  CAS  Google Scholar 

  28. Feinberg RF, Kliman HJ (1992) Fetal fibronectin and preterm labor. N Engl J Med 326:708

    Article  PubMed  CAS  Google Scholar 

  29. Zhou Y, Fisher SJ, Janatpour M, Genbacev O, Dejana E, Wheelock M, Damsky CH (1997) Human cytotrophoblasts adopt a vascular phenotype as they differentiate. A strategy for successful endovascular invasion? J Clin Invest 99:2139–2151

    PubMed  CAS  Google Scholar 

  30. Fisher SJ, Damsky CH (1993) Human cytotrophoblast invasion. Semin Cell Biol 4:183–188

    Article  PubMed  CAS  Google Scholar 

  31. Menzin AW, Loret de Mola JR, Bilker WB, Wheeler JE, Rubin SC, Feinberg RF (1998) Identification of oncofetal fibronectin in patients with advanced epithelial ovarian cancer: detection in ascitic fluid and localization to primary sites and metastatic implants. Cancer 82:152–158

    Article  PubMed  CAS  Google Scholar 

  32. Aplin JD, Haigh T, Jones CJ, Church HJ, Vicovac L (1999) Development of cytotrophoblast columns from explanted first-trimester human placental villi: role of fibronectin and integrin alpha5beta1. Biol Reprod 60:828–838

    Article  PubMed  CAS  Google Scholar 

  33. Aplin JD, Lacey H, Haigh T, Jones CJ, Chen CP, Westwood M (2000) Growth factor-extracellular matrix synergy in the control of trophoblast invasion. Biochem Soc Trans 28:199–202

    PubMed  CAS  Google Scholar 

  34. DiFederico E, Genbacev O, Fisher SJ (1999) Preeclampsia is associated with widespread apoptosis of placental cytotrophoblasts within the uterine wall. Am J Pathol 155:293–301

    PubMed  CAS  Google Scholar 

  35. Kadyrov M, Schmitz C, Black S, Kaufmann P, Huppertz B (2003) Pre-eclampsia and maternal anaemia display reduced apoptosis and opposite invasive phenotypes of extravillous trophoblast. Placenta 24:540–548

    Article  PubMed  CAS  Google Scholar 

  36. Kadyrov M, Kingdom JC, Huppertz B (2006) Divergent trophoblast invasion and apoptosis in placental bed spiral arteries from pregnancies complicated by maternal anemia and early-onset preeclampsia/intrauterine growth restriction. Am J Obstet Gynecol 194:557–563

    Article  PubMed  Google Scholar 

  37. Reister F, Frank HG, Heyl W, Kosanke G, Huppertz B, Schroder W, Kaufmann P, Rath W (1999) The distribution of macrophages in spiral arteries of the placental bed in pre-eclampsia differs from that in healthy patients. Placenta 20:229–233

    Article  PubMed  CAS  Google Scholar 

  38. Reister F, Frank HG, Kingdom JC, Heyl W, Kaufmann P, Rath W, Huppertz B (2001) Macrophage-induced apoptosis limits endovascular trophoblast invasion in the uterine wall of preeclamptic women. Lab Invest 81:1143–1152

    PubMed  CAS  Google Scholar 

  39. Zybina TG, Frank HG, Biesterfeld S, Kaufmann P (2004) Genome multiplication of extravillous trophoblast cells in human placenta in the course of differentiation and invasion into endometrium and myometrium. II. Mechanisms of polyploidization. Tsitologiia 46:640–648

    PubMed  CAS  Google Scholar 

  40. Kaufmann P, Black S, Huppertz B (2003) Endovascular trophoblast invasion: implications for the pathogenesis of intrauterine growth retardation and preeclampsia. Biol Reprod 69:1–7

    Article  PubMed  CAS  Google Scholar 

  41. Pijnenborg R (1990) Trophoblast invasion and placentation in the human: morphological aspects. Trophoblast Res 4:33–47

    Google Scholar 

  42. Craven CM, Morgan T, Ward K (1998) Decidual spiral artery remodelling begins before cellular interaction with cytotrophoblasts. Placenta 19:241–252

    Article  PubMed  CAS  Google Scholar 

  43. Hees H, Moll W, Wrobel KH, Hees I (1987) Pregnancy-induced structural changes and trophoblastic invasion in the segmental mesometrial arteries of the guinea pig (Cavia porcellus L.). Placenta 8:609–626

    PubMed  CAS  Google Scholar 

  44. Moll W, Nienartowicz A, Hees H, Wrobel KH, Lenz A (1988) Blood flow regulation in the uteroplacental arteries. Trophoblast Res 3:83–96

    Google Scholar 

  45. Nanaev A, Chwalisz K, Frank HG, Kohnen G, Hegele-Hartung C, Kaufmann P (1995) Physiological dilation of uteroplacental arteries in the guinea pig depends on nitric oxide synthase activity of extravillous trophoblast. Cell Tissue Res 282:407–421

    PubMed  CAS  Google Scholar 

  46. Hirano H, Ima, Y, Ito H (2002) Spiral artery of placenta: development and pathology-immunohistochemical, microscopical, and electron-microscopic study. Kobe J Med Sci 48:13–23

    PubMed  Google Scholar 

  47. Robertson WB (1976) Uteroplacental vasculature. J Clin Pathol Suppl 10:9–17

    CAS  Google Scholar 

  48. De Wolf F, De Wolf-Peeters C, Brosens I (1973) Ultrastructure of the spiral arteries in the human placental bed at the end of normal pregnancy. Am J Obstet Gynecol 117:833–848

    PubMed  Google Scholar 

  49. Pijnenborg R, Bland JM, Robertson WB, Dixon G, Brosens I (1981) The pattern of interstitial trophoblastic invasion of the myometrium in early human pregnancy. Placenta 2:303–316

    PubMed  CAS  Google Scholar 

  50. Jauniaux E, Hempstock J, Greenwold N, Burton GJ (2003) Trophoblastic oxidative stress in relation to temporal and regional differences in maternal placental blood flow in normal and abnormal early pregnancies. Am J Pathol 162:115–125

    PubMed  Google Scholar 

  51. Hustin J, Jauniaux E, Schaaps JP (1990) Histological study of the materno-embryonic interface in spontaneous abortion. Placenta 11:477–486

    Article  PubMed  CAS  Google Scholar 

  52. Brosens IA (1988) The utero-placental vessels at term—the distribution and extent of physiological changes. Trophoblast Res 3:61–67

    Google Scholar 

  53. Sheppard BL, Bonnar J (1988) The maternal blood supply to the placenta in pregnancy complicated by intrauterine fetal growth retardation. Trophoblast Res 3:69–81

    Google Scholar 

  54. Dempsey EW (1972) The development of capillaries in the villi of early human placentas. Am J Anat 134:221–238

    Article  PubMed  CAS  Google Scholar 

  55. Demir R, Kaufmann P, Castellucci M, Erbengi T, Kotowski A (1989) Fetal vasculogenesis and angiogenesis in human placental villi. Acta Anat 136:190–203

    PubMed  CAS  Google Scholar 

  56. Corner GW (1929) A well-preserved human embryo of 10 somites. Carnegie Contrib Embryol 20:81–102

    Google Scholar 

  57. Hustin J, Schaaps JP (1987) Echographic and anatomic studies of the maternotrophoblastic border during the first trimester of pregnancy. Am J Obstet Gynecol 157:162–168

    PubMed  CAS  Google Scholar 

  58. Burton GJ, Jauniaux E, Watson AL (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

    Article  PubMed  CAS  Google Scholar 

  59. Schaaps JP, Hustin J (1988) In vivo aspect of the maternal-trophoblastic border during the first trimester of gestation. Trophoblast Res 3:39–48

    Google Scholar 

  60. Burton GJ, Watson AL, Hempstock J, Skepper JN, Jauniaux E (2002) Uterine glands provide histiotrophic nutrition for the human fetus during the first trimester of pregnancy. J Clin Endocrinol Metab 87:2954–2959

    Article  PubMed  CAS  Google Scholar 

  61. Amoroso EC (1952) Placentation. In: Parkes AS (ed) Marshall’s physiology of reproduction. Longmans, London, pp 127–311

    Google Scholar 

  62. Lennard SN, Gerstenberg C, Allen WR, Stewart F (1998) Expression of epidermal growth factor and its receptor in equine placental tissues. J Reprod Fertil 112:49–57

    Article  PubMed  CAS  Google Scholar 

  63. Gray CA, Taylor KM, Ramsey WS, Hill JR, Bazer FW, Bartol FF, Spencer TE (2001) Endometrial glands are required for preimplantation conceptus elongation and survival. Biol Reprod 64:1608–1613

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  65. Burton GJ, Hempstock J, Jauniaux E (2003) Oxygen, early embryonic metabolism and free radical-mediated embryopathies. Reprod BioMed Online 6:84–96

    Article  PubMed  Google Scholar 

  66. Jauniaux E, Watson AL, Hempstock J, Bao YP, Skepper JN, Burton GJ (2000) Onset of maternal arterial bloodflow and placental oxidative stress; a possible factor in human early pregnancy failure. Am J Pathol 157:2111–2122

    PubMed  CAS  Google Scholar 

  67. Nicol CJ, Zielenski J, Tsui L-C, Wells PG (2000) An embryoprotective role for glucose-6-phosphate dehydrogenase in developmental oxidative stress and chemical teratogenesis. FASEB J 14:111–127

    PubMed  CAS  Google Scholar 

  68. Jauniaux E, Gulbis B, Burton GJ (2003) The human first trimester gestational sac limits rather than facilitates oxygen transfer to the fetus—a review. Placenta 24(Suppl A):S86–S93

    Article  PubMed  Google Scholar 

  69. Watson AL, Skepper JN, Jauniaux E, Burton GJ (1998) Susceptibility of human placental syncytiotrophoblastic mitochondria to oxygen-mediated damage in relation to gestational age. J Clin Endocrinol Metab 83:1697–1705

    Article  PubMed  CAS  Google Scholar 

  70. Mayhew TM, Leach L, McGee R, Ismail WW, Myklebust R, Lammiman MJ (1999) Proliferation, differentiation and apoptosis in villous trophoblast at 13–41 weeks of gestation (including observations on annulate lamellae and nuclear pore complexes. Placenta 20:407–422

    Article  PubMed  CAS  Google Scholar 

  71. Simpson RA, Mayhew TM, Barnes PR (1992) From 13 weeks to term, the trophoblast of human placenta grows by the continuous recruitment of new proliferative units: a study of nuclear number using the disector. Placenta 13:501–512

    PubMed  CAS  Google Scholar 

  72. Bright NA, Ockleford CD (1994) Heterogeneity of Fc gamma receptor-bearing cells in human term amniochorion. Placenta 15:247–255

    Article  PubMed  CAS  Google Scholar 

  73. DeLoia JA, Burlingame JM, Krasnow JS (1997) Differential expression of G1 cyclins during human placentogenesis. Placenta 18:9–16

    Article  PubMed  CAS  Google Scholar 

  74. Olvera M, Harris S, Amezcua CA, McCourty A, Rezk S, Koo C, Felix JC, Brynes RK (2001) Immunohistochemical expression of cell cycle proteins E2F-1, Cdk-2, cyclin E, p27(kip1), and Ki-67 in normal placenta and gestational trophoblastic disease. Mod Pathol 14:1036–1042

    Article  PubMed  CAS  Google Scholar 

  75. Kaufmann P (1972) Untersuchungen über die Langhanszellen in der menschlichen Placenta. Zeitschrift fur Zellforschung 128:283–302

    Article  CAS  Google Scholar 

  76. Martin BJ, Spicer SS (1973) Ultrastructural features of cellular maturation and aging in human trophoblast. J Ultrastruct Res 43:133–149

    PubMed  CAS  Google Scholar 

  77. Boyd JD, Hamilton WJ (1966) Electron microscopic observations on the cytotrophoblast contribution to the syncytium in the human placenta. J Anat 100:535–548

    PubMed  CAS  Google Scholar 

  78. Huppertz B, Frank HG, Kingdom JC, Reister F, Kaufmann P (1998) Villous cytotrophoblast regulation of the syncytial apoptotic cascade in the human placenta. Histochem Cell Biol 110:495–508

    Article  PubMed  CAS  Google Scholar 

  79. Huppertz B, Frank HG, Reister F, Kingdom J, Korr H, Kaufmann P (1999) Apoptosis cascade progresses during turnover of human trophoblast: analysis of villous cytotrophoblast and syncytial fragments in vitro. Lab Invest 79:1687–1702

    PubMed  CAS  Google Scholar 

  80. Huppertz B, Frank HG, Kaufmann P (1999) The apoptosis cascade-morphological and immunohistochemical methods for its visualization. Anat Embryol (Berlin) 200:1–18

    Article  CAS  Google Scholar 

  81. Huppertz B, Tews DS, Kaufmann P (2001) Apoptosis and syncytial fusion in human placental trophoblast and skeletal muscle. Int Rev Cytol 205:215–253

    Article  PubMed  CAS  Google Scholar 

  82. Huppertz B, Kingdom JC (2004) Apoptosis in the trophoblast-role of apoptosis in placental morphogenesis. J Soc Gynecol Investig 11:353–362

    Article  PubMed  CAS  Google Scholar 

  83. Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257

    PubMed  CAS  Google Scholar 

  84. Nelson DM (1996) Apoptotic changes occur in syncytiotrophoblast of human placental villi where fibrin type fibrinoid is deposited at discontinuities in the villous trophoblast. Placenta 17:387–391

    Article  PubMed  CAS  Google Scholar 

  85. Ikle FA (1964) Trophoblastzellen im strömenden Blut. Schweiz Med Wochenschr 91:934–945

    Google Scholar 

  86. Huppertz B, Kaufmann P, Kingdom J (2002) Trophoblast turnover in health and disease. Fetal Maternal Med Rev 13:103–118

    Article  Google Scholar 

  87. Johansen M, Redman CW, Wilkins T, Sargent IL (1999) Trophoblast deportation in human pregnancy—its relevance for pre-eclampsia. Placenta 20:531–539

    Article  PubMed  CAS  Google Scholar 

  88. Lunetta P, Penttila A (1996) Immunohistochemical identification of syncytiotrophoblastic cells and megakaryocytes in pulmonary vessels in a fatal case of amniotic fluid embolism. Int J Legal Med 108:210–214

    Article  PubMed  CAS  Google Scholar 

  89. Cohle SD, Petty CS (1985) Sudden death caused by embolization of trophoblast from hydatidiform mole. J Forensic Sci 30:1279–1283

    PubMed  CAS  Google Scholar 

  90. Delmis J, Pfeifer D, Ivanisevic M, Forko JI, Hlupic L (2000) Sudden death from trophoblastic embolism in pregnancy. Eur J Obstet Gynecol Reprod Biol 92:225–227

    Article  PubMed  CAS  Google Scholar 

  91. Kamoi S, Ohaki Y, Mori O, Satomi M, Takahashi H, Kawamura T, Araki T (2003) Placental villotrophoblastic pulmonary emboli after elective abortion: immunohistochemical diagnosis and comparison with ten control cases. Int J Gynecol Pathol 22:303–309

    Article  PubMed  Google Scholar 

  92. Knight M, Redman CW, Linton EA, Sargent IL (1998) Shedding of syncytiotrophoblast microvilli into the maternal circulation in pre-eclamptic pregnancies. Br J Obstet Gynaecol 105:632–640

    PubMed  CAS  Google Scholar 

  93. Lee W, Ginsburg KA, Cotton DB, Kaufman RH (1986) Squamous and trophoblastic cells in the maternal pulmonary circulation identified by invasive hemodynamic monitoring during the peripartum period. Am J Obstet Gynecol 155:999–1001

    PubMed  CAS  Google Scholar 

  94. Formigli L, Papucci L, Tani A, Schiavone N, Tempestini A, Orlandini GE, Capaccioli S, Orlandini SZ (2000) Aponecrosis: morphological and biochemical exploration of a syncretic process of cell death sharing apoptosis and necrosis. J Cell Physiol 182:41–49

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Harrachgasse 21/7, 8010, Graz, Austria

    Berthold Huppertz

Authors
  1. Berthold Huppertz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Berthold Huppertz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huppertz, B. The feto–maternal interface: setting the stage for potential immune interactions. Semin Immunopathol 29, 83–94 (2007). https://doi.org/10.1007/s00281-007-0070-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00281-007-0070-7

Keywords

Search

Navigation