Wiener Medizinische Wochenschrift

, Volume 162, Issue 9–10, pp 187–190 | Cite as

The role of the invasive, placental trophoblast in human pregnancy

Main topic

Summary

During early pregnancy the placenta-derived extravillous trophoblast starts to invade the maternal uterus in order to regulate adequate blood flow and nutrient supply to the growing fetus. A unique set of events including plugging and remodelling of maternal vessels, regulation of oxygen levels, as well as the crosstalk with maternal decidual cells are thought to be precisely controlled by the invading extravillous trophoblasts. However, defects in these processes can lead to severe complications during pregnancy threatening the well-being of both the mother and the developing fetus. For instance incomplete trophoblast-associated invasion and arterial remodelling are associated with preeclampsia, the most common pregnancy-related complication. Moreover, failure in proper placental development and adequate fetal nutrition could be effective later in life, as growth-restricted neonates have a higher risk to develop adult onset of hypertension, heart disease and diabetes mellitus. Consequently, a detailed understanding of the mechanisms that underlie trophoblast invasion is thought to improve both diagnosis and treatment of various pregnancy-related disorders.

Keywords

Human placenta Trophoblast invasion Spiral artery remodelling pregnancy-related pathologies uNK cell 

Die Rolle des invasiven, plazentaren Trophoblasten in der Schwangerschaft

Zusammenfassung

Während der frühen Schwangerschaft invadiert der von der Plazenta stammende extravillöse Trophoblast den mütterlichen Uterus, um den wachsenden Föten mit Blut und Nährstoffen zu versorgen. Der extravillöse Trophoblast kontrolliert eine Reihe von einzigartigen Vorgängen, wie zum Beispiel Blockierung und Umbau von mütterlichen Gefäßen, Regulation des Sauerstoffgehaltes sowie die Kommunikation mit mütterlichen dezidualen Zellen. Treten jedoch Defekte in diesen Prozessen auf, so können diese zu schwerwiegenden Komplikationen während der Schwangerschaft, bis hin zur Gefährdung der mütterlichen und fötalen Gesundheit, führen. Zu geringe Trophoblasten-Invasion und unvollständiger Umbau der uterinen Spiralarteriolen sind zum Beispiel mit der Präeklampsie, der häufigsten Komplikation während der Schwangerschaft, assoziiert. Fehler in der plazentären Entwicklung und adäquaten Ernährung des Föten können zur fetalen Wachstumsretardierung führen und somit das Risiko für Bluthochdruck, Herzkrankheiten und Diabetes mellitus im späteren Leben erhöhen. Folglich kann postuliert werden, dass ein detailliertes Verständnis der grundlegenden Mechanismen der Trophoblasteninvasion, dazu beitragen kann, Diagnose und Behandlung verschiedenster Schwangerschaftserkrankungen zu verbessern.

Schlüsselwörter

Humane Plazenta Trophoblasteninvasion Umbau von Spiralarteriolen Pathologien in der Schwangerschaft uNK Zelle 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literature

  1. Knofler M, Pollheimer J. IFPA Award in Placentology lecture: molecular regulation of human trophoblast invasion. Placenta, 33 (Suppl): S55–S62, 2012PubMedCrossRefGoogle Scholar
  2. Caniggia I, Mostachfi H, Winter J, Gassmann M, Lye SJ, Kuliszewski M, Post M. Hypoxia-inducible factor-1 mediates the biological effects of oxygen on human trophoblast differentiation through TGFbeta[3]. J Clin Invest, 105: 577–587, 2000PubMedCrossRefGoogle Scholar
  3. Lacey H, Haigh T, Westwood M, Aplin JD. Mesenchymally-derived insulin-like growth factor 1 provides a paracrine stimulus for trophoblast migration. BMC Dev Biol, 2: 5, 2002PubMedCrossRefGoogle Scholar
  4. Moser G, Gauster M, Orendi K, Glasner A, Theuerkauf R, Huppertz B. Endoglandular trophoblast, an alternative route of trophoblast invasion? Analysis with novel confrontation co-culture models. Hum Reprod, 25: 1127–1136, 2010PubMedCrossRefGoogle Scholar
  5. Pijnenborg R, Vercruysse L, Hanssens M. The uterine spiral arteries in human pregnancy: facts and controversies. Placenta, 27: 939–958, 2006PubMedCrossRefGoogle Scholar
  6. Burton GJ, Jauniaux E, Charnock-Jones DS. The influence of the intrauterine environment on human placental development. Int J Dev Biol, 54: 303–312, 2010PubMedCrossRefGoogle Scholar
  7. Hustin J, Jauniaux E, Schaaps JP. Histological study of the materno-embryonic interface in spontaneous abortion. Placenta, 11: 477–486, 1990PubMedCrossRefGoogle Scholar
  8. Naicker T, Khedun SM, Moodley J, Pijnenborg R. Quantitative analysis of trophoblast invasion in preeclampsia. Acta Obstet Gynecol Scand, 82: 722–729, 2003PubMedCrossRefGoogle Scholar
  9. Brosens I, Dixon HG, Robertson WB. Fetal growth retardation and the arteries of the placental bed. Br J Obstet Gynaecol, 84: 656–663, 1977PubMedGoogle Scholar
  10. van Dijk M, Mulders J, Poutsma A, Konst AA, Lachmeijer AM, Dekker GA, Blankenstein MA, Oudejans CB. Maternal segregation of the Dutch preeclampsia locus at 10q22 with a new member of the winged helix gene family. Nat Genet, 37: 514–519, 2005PubMedCrossRefGoogle Scholar
  11. van Dijk M, van Bezu J, van Abel D, Dunk C, Blankenstein MA, Oudejans CB, Lye SJ. The STOX1 genotype associated with pre-eclampsia leads to a reduction of trophoblast invasion by alpha-T-catenin upregulation. Hum Mol Genet, 19: 2658–2667, 2010PubMedCrossRefGoogle Scholar
  12. Pollheimer J, Loregger T, Sonderegger S, Saleh L, Bauer S, Bilban M, Czerwenka K, Husslein P, Knofler M. Activation of the canonical wingless/T-cell factor signaling pathway promotes invasive differentiation of human trophoblast. Am J Pathol, 168: 1134–1147, 2006PubMedCrossRefGoogle Scholar
  13. Sonderegger S, Haslinger P, Sabri A, Leisser C, Otten JV, Fiala C, Knofler M. Wingless (Wnt)-3A induces trophoblast migration and matrix metalloproteinase-2 secretion through canonical Wnt signaling and protein kinase B/AKT activation. Endocrinology, 151: 211–220, 2010PubMedCrossRefGoogle Scholar
  14. Pollheimer J, Knofler M. Signalling pathways regulating the invasive differentiation of human trophoblasts: a review. Placenta, 26 (Suppl A): S21–S30, 2005PubMedCrossRefGoogle Scholar
  15. Harris LK, Smith SD, Keogh RJ, Jones RL, Baker PN, Knofler M, Cartwright JE, Whitley GS, Aplin JD. Trophoblast- and vascular smooth muscle cell-derived MMP-12 mediates elastolysis during uterine spiral artery remodeling. Am J Pathol, 177: 2103–2115, 2010PubMedCrossRefGoogle Scholar
  16. Lala PK, Chakraborty C. Factors regulating trophoblast migration and invasiveness: possible derangements contributing to pre-eclampsia and fetal injury. Placenta, 24: 575–587, 2003PubMedCrossRefGoogle Scholar
  17. Hirtenlehner K, Pollheimer J, Lichtenberger C, Wolschek MF, Zeisler H, Husslein P, Knofler M. Elevated serum concentrations of the angiogenesis inhibitor endostatin in preeclamptic women. J Soc Gynecol Investig, 10: 412–417, 2003PubMedCrossRefGoogle Scholar
  18. Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, Schisterman EF, Thadhani R, Sachs BP, Epstein FH, Sibai BM, Sukhatme VP, Karumanchi SA. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med, 350: 672–683, 2004PubMedCrossRefGoogle Scholar
  19. Pollheimer J, Husslein P, Knofler M. Invasive trophoblasts generate regulatory collagen XVIII cleavage products. Placenta, 26 (Suppl A): S42–S45, 2005PubMedCrossRefGoogle Scholar
  20. Pollheimer J, Bauer S, Huber A, Husslein P, Aplin JD, Knofler M Expression pattern of collagen XVIII and its cleavage product, the angiogenesis inhibitor endostatin, at the fetal-maternal interface. Placenta, 25: 770–779, 2004PubMedCrossRefGoogle Scholar
  21. Pollheimer J, Haslinger P, Fock V, Prast J, Saleh L, Biadasiewicz K, Jetne-Edelmann R, Haraldsen G, Haider S, Hirtenlehner-Ferber K, Knofler M. Endostatin suppresses IGF-II-mediated signaling and invasion of human extravillous trophoblasts. Endocrinology, 152: 4431–4442, 2011PubMedCrossRefGoogle Scholar
  22. Guibourdenche J, Handschuh K, Tsatsaris V, Gerbaud P, Leguy MC, Muller F, Brion DE, Fournier T. Hyperglycosylated hCG is a marker of early human trophoblast invasion. J Clin Endocrinol Metab, 95: E240–E244, 2010PubMedCrossRefGoogle Scholar
  23. Prast J, Saleh L, Husslein H, Sonderegger S, Helmer H, Knofler M. Human chorionic gonadotropin stimulates trophoblast invasion through extracellularly regulated kinase and AKT signaling. Endocrinology, 149: 979–987, 2008PubMedCrossRefGoogle Scholar
  24. Tranchot-Diallo J, Gras G, Parnet-Mathieu F, Benveniste O, Marce D, Roques P, Milliez J, Chaouat G, Dormont D. Modulations of cytokine expression in pregnant women. Am J Reprod Immunol, 37: 215–226, 1997PubMedCrossRefGoogle Scholar
  25. Lin H, Mosmann TR, Guilbert L, Tuntipopipat S, Wegmann TG. Synthesis of T helper 2-type cytokines at the maternal-fetal interface. J Immunol, 151: 4562–4573, 1993PubMedGoogle Scholar
  26. Roth I, Corry DB, Locksley RM, Abrams JS, Litton MJ, Fisher SJ. Human placental cytotrophoblasts produce the immunosuppressive cytokine interleukin 10. J Exp Med, 184: 539–548, 1996PubMedCrossRefGoogle Scholar
  27. Chaouat G, Assal Meliani A, Martal J, Raghupathy R, Elliott JF, Mosmann T, Wegmann TG. IL-10 prevents naturally occurring fetal loss in the CBA x DBA/2 mating combination, and local defect in IL-10 production in this abortion-prone combination is corrected by in vivo injection of IFN-tau. J Immunol, 154: 4261–4268, 1995PubMedGoogle Scholar
  28. Challis JR, Lockwood CJ, Myatt L, Norman JE, Strauss JF 3rd, Petraglia F. Inflammation and pregnancy. Reprod Sci, 16: 206–215, 2009PubMedCrossRefGoogle Scholar
  29. Hanna J, Goldman-Wohl D, Hamani Y, Avraham I, Greenfield C, Natanson-Yaron S, Prus D, Cohen-Daniel L, Arnon TI, Manaster I, Gazit R, Yutkin V, Benharroch D, Porgador A, Keshet E, Yagel S, Mandelboim O. Decidual NK cells regulate key developmental processes at the human fetal-maternal interface. Nat Med, 12: 1065–1074, 2006PubMedCrossRefGoogle Scholar
  30. Hazan AD, Smith SD, Jones RL, Whittle W, Lye SJ, Dunk CE. Vascular-leukocyte interactions: mechanisms of human decidual spiral artery remodeling in vitro. Am J Pathol, 177: 1017–1030, 2010PubMedCrossRefGoogle Scholar
  31. Hiby SE, Apps R, Sharkey AM, Farrell LE, Gardner L, Mulder A, Claas FH, Walker JJ, Redman CW, Morgan L, Tower C, Regan L, Moore GE, Carrington M, Moffett A. Maternal activating KIRs protect against human reproductive failure mediated by fetal HLA-C2. J Clin Invest, 120: 4102–4110, 2010PubMedCrossRefGoogle Scholar
  32. Moffett A, Loke C. Immunology of placentation in eutherian mammals. Nat Rev Immunol, 6: 584–594, 2006PubMedCrossRefGoogle Scholar
  33. Chazara O, Xiong S, Moffett A. Maternal KIR and fetal HLA-C: a fine balance. J Leukoc Biol, 90: 703–716, 2011PubMedCrossRefGoogle Scholar
  34. Colucci F, Boulenouar S, Kieckbusch J, Moffett A. How does variability of immune system genes affect placentation? Placenta, 32: 539–545, 2011PubMedCrossRefGoogle Scholar
  35. Longtine MS, Nelson DM.Placental dysfunction and fetal programming: the importance of placental size, shape, histopathology, and molecular composition. Semin Reprod Med, 29: 187–196, 2011PubMedCrossRefGoogle Scholar
  36. Nicoletto SF, Rinaldi A. In the womb's shadow. The theory of prenatal programming as the fetal origin of various adult diseases is increasingly supported by a wealth of evidence. EMBO Rep, 12: 30–34, 2011PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Reproductive Biology Unit, Department of Obstetrics and Fetal-Maternal MedicineMedical University of ViennaViennaAustria

Personalised recommendations