Skip to main content
SpringerLink
Log in
Book cover

Cell Fusion in Health and Disease pp 103–112Cite as

Human Trophoblast in Trisomy 21: A Model for Cell–Cell Fusion Dynamic Investigation

  • Chapter
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 950))

Abstract

Trophoblastic cell fusion is one essential step of the human trophoblast differentiation leading to formation of the syncytiotrophoblast, site of the numerous placental functions. This process is multifactorial and finely regulated. Using the physiological model of primary culture of trophoblastic cells isolated from human placenta, we have identified different membrane proteins directly involved in trophoblastic cell fusion: connexin 43, ZO-1 and recently syncytins. These fusogenic membrane retroviral envelop glycoproteins: syncytin-1 (encoded by the HERV-W gene) and syncytin-2 (encoded by the FRD gene) and their receptors are major factors involved in human placental development. Disturbances of syncytiotrophoblast formation are observed in trisomy 21-affected placentas. Overexpression of the copper/zinc superoxide dismutase (SOD-1), encoded by chromosome 21 as well as an abnormal hCG signaling are implicated in the defect of syncytiotrophoblast formation. This abnormal trophoblast fusion and differentiation in trisomy 21-affected placenta is reversible in vitro by different ways.

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

References

  1. Benirschke K, Kaufmann P (2000) Pathology of the placenta. Springer, New York, NY

    Google Scholar 

  2. Malassine A, Frendo JL, Evain-Brion D (2003) A comparison of placental development and endocrine functions between the human and mouse model. Hum Reprod Update 9:531–539

    Article  PubMed  CAS  Google Scholar 

  3. Evain-Brion D, Malassine A (2003) Human placenta as an endocrine organ. Growth Horm IGF Res 13(Suppl A):S34–S37

    Article  PubMed  CAS  Google Scholar 

  4. Alsat E, Mirlesse V, Fondacci C et al (1991) Parathyroid hormone increases epidermal growth factor receptors in cultured human trophoblastic cells from early and term placenta. J Clin Endocrinol Metab 73:288–295

    Article  PubMed  CAS  Google Scholar 

  5. Kliman HJ, Nestler JE, Sermasi E et al (1986) Purification, characterization, and in vitro differentiation of cytotrophoblasts from human term placentae. Endocrinology 118:1567–1582

    Article  PubMed  CAS  Google Scholar 

  6. Getsios S, MacCalman CD (2003) Cadherin-11 modulates the terminal differentiation and fusion of human trophoblastic cells in vitro. Dev Biol 257:41–54

    Article  PubMed  CAS  Google Scholar 

  7. Dalton P, Christian HC, Redman CW et al (2007) Membrane trafficking of CD98 and its ligand galectin 3 in BeWo cells – implication for placental cell fusion. FEBS J 274:2715–2727

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  9. Frendo JL, Cronier L, Bertin G et al (2003) Involvement of connexin 43 in human trophoblast cell fusion and differentiation. J Cell Sci 116:3413–3421

    Article  PubMed  CAS  Google Scholar 

  10. Pidoux G, Gerbaud P, Gnidehou S et al (2010) ZO-1 is involved in trophoblastic cell differentiation in human placenta. Am J Physiol Cell Physiol 298:C1517–C1526

    Article  PubMed  CAS  Google Scholar 

  11. Frendo JL, Olivier D, Cheynet V et al (2003) Direct involvement of HERV-W Env glycoprotein in human trophoblast cell fusion and differentiation. Mol Cell Biol 23:3566–3574

    Article  PubMed  CAS  Google Scholar 

  12. Blaise S, de Parseval N, Benit L et al (2003) Genomewide screening for fusogenic human endogenous retrovirus envelopes identifies syncytin 2, a gene conserved on primate evolution. Proc Natl Acad Sci USA 100:13013–13018

    Article  PubMed  CAS  Google Scholar 

  13. Blond JL, Lavillette D, Cheynet V et al (2000) An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor. J Virol 74:3321–3329

    Article  PubMed  CAS  Google Scholar 

  14. Mi S, Lee X, Li X et al (2000) Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 403:785–789

    Article  PubMed  CAS  Google Scholar 

  15. de Parseval N, Heidmann T (2005) Human endogenous retroviruses: from infectious elements to human genes. Cytogen Genome Res 110:318–332

    Article  Google Scholar 

  16. Mallet F, Bouton O, Prudhomme S et al (2004) The endogenous retroviral locus ERVWE1 is a bona fide gene involved in hominoid placental physiology. Proc Natl Acad Sci USA 101:1731–1736

    Article  PubMed  CAS  Google Scholar 

  17. Gimenez J, Montgiraud C, Oriol G et al (2009) Comparative methylation of ERVWE1/syncytin-1 and other human endogenous retrovirus LTRs in placenta tissues. DNA Res 16:195–211

    Article  PubMed  CAS  Google Scholar 

  18. Liang CY, Wang LJ, Chen CP et al (2010) GCM1 regulation of the expression of Syncytin 2 and its cognate receptor MFSD2A in human placenta. Biol Reprod 83:387–395

    Article  PubMed  CAS  Google Scholar 

  19. Blaise S, de Parseval N, Heidmann T (2005) Functional characterization of two newly identified Human Endogenous Retrovirus coding envelope genes. Retrovirology 2:19

    Article  PubMed  Google Scholar 

  20. Kjeldbjerg AL, Villesen P, Aagaard L et al (2008) Gene conversion and purifying selection of a placenta-specific ERV-V envelope gene during simian evolution. BMC Evol Biol 8:266

    Article  PubMed  Google Scholar 

  21. Muir A, Lever AM, Moffett A (2006) Human endogenous retrovirus-W envelope (syncytin) is expressed in both villous and extravillous trophoblast populations. J Gen Virol 87:2067–2071

    Article  PubMed  CAS  Google Scholar 

  22. Malassine A, Lavialle C, Frendo JL et al (2010) Syncytins in normal and pathological placentas. In: Lever AML, Jeang KT, Berkhout B (eds.) Recent advances in Human Retroviruses. World Scientific, pp. 243–270

    Google Scholar 

  23. Malassine A, Handschuh K, Tsatsaris V et al (2005) Expression of HERV-W Env glycoprotein (syncytin) in the extravillous trophoblast of first trimester human placenta. Placenta 26:556–562

    Article  PubMed  CAS  Google Scholar 

  24. Malassine A, Frendo JL, Blaise S et al (2008) Human endogenous retrovirus-FRD envelope protein (syncytin 2) expression in normal and trisomy 21-affected placenta. Retrovirology 5:6

    Article  PubMed  Google Scholar 

  25. Malassine A, Frendo JL, Evain-Brion D (2010) Trisomy 21- affected placentas highlight prerequisite factors for human trophoblast fusion and differentiation. Int J Dev Biol 54:475–482

    Article  PubMed  CAS  Google Scholar 

  26. Esnault C, Priet S, Ribet D et al (2008) A placenta-specific receptor for the fusogenic, endogenous retrovirus-derived, human syncytin-2. Proc Natl Acad Sci USA 105:17532–17537

    Article  PubMed  CAS  Google Scholar 

  27. Kudaka W, Oda T, Jinno Y et al (2008) Cellular localization of placenta-specific human endogenous retrovirus (HERV) transcripts and their possible implication in pregnancy-induced hypertension. Placenta 29:282–289

    Article  PubMed  CAS  Google Scholar 

  28. Vargas A, Moreau J, Landry S et al (2009) Syncytin-2 plays an important role in the fusion of human trophoblast cells. J Mol Biol 392:301–318

    Article  PubMed  CAS  Google Scholar 

  29. Qureshi F, Jacques SM, Johnson MP et al (1997) Trisomy 21 placentas: histopathological and immunohistochemical findings using proliferating cell nuclear antigen. Fetal Diagn Ther 12:210–215

    Article  PubMed  CAS  Google Scholar 

  30. Oberweis D, Gillerot Y, Koulischer L et al (1983) The placenta in trisomy in the last trimester of pregnancy. J Gynecol Obstet Biol Reprod (Paris) 12:345–349

    CAS  Google Scholar 

  31. Roberts L, Sebire NJ, Fowler D et al (2000) Histomorphological features of chorionic villi at 10–14 weeks of gestation in trisomic and chromosomally normal pregnancies. Placenta 21:678–683

    Article  PubMed  CAS  Google Scholar 

  32. Forbes K, Westwood M, Baker PN et al (2008) Insulin-like growth factor I and II regulate the life cycle of trophoblast in the developing human placenta. Am J Physiol Cell Physiol 294:C1313–C1322

    Article  PubMed  CAS  Google Scholar 

  33. Massin N, Frendo JL, Guibourdenche J et al (2001) Defect of syncytiotrophoblast formation and human chorionic gonadotropin expression in Down’s syndrome. Placenta 22(Suppl A):S93–S97

    Article  PubMed  Google Scholar 

  34. Pidoux G, Guibourdenche J, Frendo JL et al (2004) Impact of trisomy 21 on human trophoblast behaviour and hormonal function. Placenta 25(Suppl A):S79–S84

    Article  PubMed  CAS  Google Scholar 

  35. Frendo JL, Guibourdenche J, Pidoux G et al (2004) Trophoblast production of a weakly bioactive human chorionic gonadotropin in trisomy 21-affected pregnancy. J Clin Endocrinol Metab 89:727–732

    Article  PubMed  CAS  Google Scholar 

  36. Frendo JL, Therond P, Bird T et al (2001) Overexpression of copper zinc superoxide dismutase impairs human trophoblast cell fusion and differentiation. Endocrinology 142:3638–3648

    Article  PubMed  CAS  Google Scholar 

  37. Frendo JL, Therond P, Guibourdenche J et al (2002) Implication of copper zinc superoxide dismutase (SOD-1) in human placenta development. Ann NY Acad Sci 973:297–301

    Article  PubMed  CAS  Google Scholar 

  38. Pidoux G, Gerbaud P, Marpeau O et al (2007) Human placental development is impaired by abnormal human chorionic gonadotropin signaling in trisomy 21 pregnancies. Endocrinology 148:5403–5413

    Article  PubMed  CAS  Google Scholar 

  39. Dimon-Gadal S, Gerbaud P, Keryer G et al (1998) In vitro effects of oxygen-derived free radicals on type I and type II cAMP-dependent protein kinases. J Biol Chem 273:22833–22840

    Article  PubMed  CAS  Google Scholar 

  40. Pidoux G, Tasken K (2010) Specificity and spatial dynamics of protein kinase A signaling organized by A-kinase-anchoring proteins. J Mol Endocrinol 44:271–284

    Article  PubMed  CAS  Google Scholar 

  41. Hemberger M, Udayashankar R, Tesar P et al (2010) ELF5-enforced transcriptional networks define an epigenetically regulated trophoblast stem cell compartment in the human placenta. Hum Mol Genet 19:2456–2467

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Inserm UMR 767 Paris Descartes, Fondation PremUP, 4 Avenue de l’Observatoire, 75006, Paris, France

    André Malassiné, Guillaume Pidoux, Pascale Gerbaud, Jean Louis Frendo & Danièle Evain-Brion

Authors
  1. André Malassiné
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guillaume Pidoux
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pascale Gerbaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jean Louis Frendo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Danièle Evain-Brion
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Danièle Evain-Brion .

Editor information

Editors and Affiliations

  1. Inst. Immunologie, Universität Witten/Herdecke, Stockumer Str. 10, Witten, 58448, Germany

    Thomas Dittmar

  2. Institute of Immunologie, University of Witten/Herdecke, Stockumer Str. 10, Witten, 58448, Germany

    Kurt S. Zänker

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Malassiné, A., Pidoux, G., Gerbaud, P., Frendo, J.L., Evain-Brion, D. (2011). Human Trophoblast in Trisomy 21: A Model for Cell–Cell Fusion Dynamic Investigation. In: Dittmar, T., Zänker, K. (eds) Cell Fusion in Health and Disease. Advances in Experimental Medicine and Biology, vol 950. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0782-5_4

Download citation

Publish with us

Policies and ethics

Search

Navigation