Vascular Invasion During Implantation and Placentation

  • Allen C. Enders
  • Thomas N. Blankenship
Part of the Proceedings in the Serono Symposia USA Series book series (SERONOSYMP)


In species as diverse as the golden hamster, bulldog bat, and baboon, cytotrophoblast cells originating from the embryo are thought to migrate into maternal endometrial arteries (1, 2, 3, 4, 5). In primates, including macaque monkeys, baboons, and humans, the cells not only migrate into the arteries but extensively modify the walls of these arteries, a process considered normal in establishing the definitive uteroplacental blood flow in these species (6, 7, 8, 9, 10). The functional consequences of the changes in spiral artery walls include the inability to constrict effectively in response to vasoactive stimuli. This probably helps to maintain a relatively constant maternal blood flow to the placenta regardless of changes in the physiological status of the mother. The manner in which this vascular invasion and modification occurs in macaques has been the subject of a series of recent studies in our laboratory. This chapter summarizes and interprets the results of these studies to date.


Vascular Invasion Trophoblast Cell Neural Cell Adhesion Molecule Artery Wall Tunica Medium 
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  1. 1.
    Pijnenborg R, Robertson WB, Brosens I. The arterial migration of trophoblast in the uterus of the golden hamster, Mesocricetus auratus. J Reprod Fert 1974;40:269–80.CrossRefGoogle Scholar
  2. 2.
    Pijnenborg R, Robertson WB, Brosens I, Dixon G. Review article: invasion and the establishment of haemochorial placentation in man and laboratory animals. Placenta 1981;2:71–92.PubMedCrossRefGoogle Scholar
  3. 3.
    Rasweiler JJ IV. Pregnancy in chiroptera. J Exp Zool 1993;266:495–513.PubMedCrossRefGoogle Scholar
  4. 4.
    Carpenter SJ. Trophoblast invasion and alteration of mesometrial arteries in the pregnant hamster: light and electron microscopic observations. Placenta 1982;3:219–42.PubMedCrossRefGoogle Scholar
  5. 5.
    Tarara R, Enders AC, Hendrickx AG, Gulamhusein N, Hodges JK, Hearn JP et al. Early implantation and embryonic development of the baboon: stages 5, 6, and 7. Anat Embryol 1987;176:267–75.PubMedCrossRefGoogle Scholar
  6. 6.
    Harris JWS, Ramsey EM. The morphology of human uteroplacental vasculature. Contrib Embryol Carnegie Inst 1966;38:43–58.Google Scholar
  7. 7.
    Ramsey EM, Harris JWS. Comparison of uteroplacental vasculature and circulation in the rhesus monkey and man. Contrib Embryol Carnegie Inst 1966;38:58–70.Google Scholar
  8. 8.
    Brosens IA, Robertson WB, Dixon HG. The physiological response of the vessels of the placental bed to normal pregnancy. J Pathol Bact 1967;93:569–79.CrossRefGoogle Scholar
  9. 9.
    Ramsey EM, Houston ML, Harris JWS. Interactions of the trophoblast and maternal tissues in three closely related primate species. Am J Obstet Gynecol 1976;124: 647–52.PubMedGoogle Scholar
  10. 10.
    Blankenship TN, Enders AC, King BF. Trophoblastic invasion and the development of uteroplacental arteries in the macaque: Immunohistochemical localization of cytokeratins, desmin, type IV collagen, laminin, and fibronectin. Cell Tissue Res 1993;272:227–36.PubMedCrossRefGoogle Scholar
  11. 11.
    Enders AC, Hendrickx AG, Schlafke S. Implantation in the rhesus monkey: initial penetration of endometrium. Am J Anat 1983;167:275–98.PubMedCrossRefGoogle Scholar
  12. 12.
    Enders AC. Trophoblast differentiation during the transition from trophoblastic plate to lacunar stage of implantation in the rhesus monkey and human. Am J Anat 1989;186: 85–98.PubMedCrossRefGoogle Scholar
  13. 13.
    Enders AC, King BF. Early stages of trophoblastic invasion of the maternal vascular system during implantation in the macaque and baboon. Am J Anat 1991;192:329–46.PubMedCrossRefGoogle Scholar
  14. 14.
    Enders AC, Lantz KC, Schlafke S. Preference of invasive cytotrophoblast for maternal vessels in early implantation in the macaque. Acta Anat 1996;155:145–62.PubMedCrossRefGoogle Scholar
  15. 15.
    Enders AC. Cytodifferentiation of trophoblast in the anchoring villi and trophoblastic shell in the first half of gestation in the macaque. Micros Res Tech 1997;38:3–20.CrossRefGoogle Scholar
  16. 16.
    Enders AC. The transition from lacunar to villous stage of implantation in the macaque, including establishment of the trophoblastic shell. Acta Anat 1995;152:151–69.PubMedCrossRefGoogle Scholar
  17. 17.
    Blankenship TN, Enders AC, King BE. Distribution of laminin, type IV collagen, and fibronectin in the cell columns and cytotrophoblastic shell of early macaque placentas. Cell Tissue Res 1992;270:241–8.PubMedCrossRefGoogle Scholar
  18. 18.
    King BF, Blankenship TN. Differentiation of the chorionic plate of the placenta: cellular and extracellular matrix changes during development in the macaque. Anat Rec 1994;240:267–76.PubMedCrossRefGoogle Scholar
  19. 19.
    Blankenship TN, King BF. Macaque intra-arterial trophoblast and extravillous trophoblast of the cell columns and cytotrophoblastic shell express neural cell adhesion molecule (NCAM). Anat Rec 1996;245:525–31.PubMedCrossRefGoogle Scholar
  20. 20.
    Blankenship TN, Enders AC. Expression of platelet-endothelial cell adhesion molecule-1 (PECAM) by macaque trophoblast cells during invasion of the spiral arteries. Anat Rec 1997;247:413–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Blankenship TN, Enders AC, King BF. Trophoblastic invasion and modification of uterine veins during placental development in macaques. Cell Tissue Res 1993;274: 135–44.PubMedCrossRefGoogle Scholar
  22. 22.
    Genbacev O, Zhou Y, Ludlow JW, Fisher SJ. Regulation of human placental development by oxygen tension. Science 1997;277:1660–72.CrossRefGoogle Scholar
  23. 23.
    Hawes CS, Suskin HA, Petropoulas A, Latham SE, Mueller UW. A morphologic study of trophoblast isolated from peripheral blood of pregnant women. Am J Obstet Gynecol 1994;170:1297–300.PubMedGoogle Scholar
  24. 24.
    Boyd JD, Hamilton WJ. The human placenta. Cambridge: Heffer, 1970.Google Scholar
  25. 25.
    Blankenship TN, King BF. Identification of 72-kilodalton type IV collagenase at sites of trophoblastic invasion of macaque spiral arteries. Placenta 1994;15:177–87.PubMedCrossRefGoogle Scholar
  26. 26.
    Blankenship TN, Enders AC. Trophoblast cell-mediated modifications to uterine spiral arteries during early gestation in the macaque. Acta Anat 1997;158:227–36.PubMedCrossRefGoogle Scholar
  27. 27.
    Blankenship TN, King BF. Developmental expression of Ki-67 antigen and proliferating cell nuclear antigen (PCNA) in macaque placentas. Devel Dynamics 1994;201:324–33.CrossRefGoogle Scholar
  28. 28.
    Blankenship TN, King BF. Developmental changes in the cell columns and trophoblastic shell of the macaque placenta: an immunohistochemical study localizing type IV collagen, laminin, fibronectin and cytokeratins. Cell Tissue Res 1993;274:457–66.PubMedCrossRefGoogle Scholar
  29. 29.
    King BF, Blankenship TN. Ultrastructure and development of a thick basement membrane-like layer in the anchoring villi of macaque placentas. Anat Rec 1994;238: 498–506.PubMedCrossRefGoogle Scholar
  30. 30.
    Kurman RJ, Main CS, Chen HC. Intermediate trophoblast: a distinctive form of trophoblast with specific morphological, biochemical and structural features. Placenta 1984;5:349–70.PubMedCrossRefGoogle Scholar
  31. 31.
    Enders AC. Cytotrophoblast invasion of the endometrium in the human and macaque stage of implantation. Troph Res 1997;10:83–95.Google Scholar
  32. 32.
    Zhou Y, Fisher SJ, Janatpour M, Genbacev O, Dejana E, Wheelock M et al. Human cytotrophoblasts adopt a vascular phenotype as they differentiate: a strategy for successful endovascular invasion? J Clin Invest 1997;99:2139–51.PubMedCrossRefGoogle Scholar
  33. 33.
    Vicovac L, Aplin JD. Epithelial-mesenchymal transition during trophoblast differentiation. Acta Anat 1996;156:202–16.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Allen C. Enders
  • Thomas N. Blankenship

There are no affiliations available

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