title: Human trophoblast in trisomy 21: a model for cell-cell fusion dynamic investigation.
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.
authors.affiliation: Inserm UMR 767 Paris Descartes, Fondation PremUP, 4 Avenue de l'Observatoire, 75006, Paris, France. andre.malassine@parisdescartes.fr
authors.forename: André
authors.initials: A
authors.lastname: Malassiné
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pidoux
authors.forename: Pascale
authors.initials: P
authors.lastname: Gerbaud
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Frendo
authors.forename: Danièle
authors.initials: D
authors.lastname: Evain-Brion
mesh_terms: D002454:Cell Differentiation; D002459:Cell Fusion; D004314:Down Syndrome / Q000473:pathology*; D015686:Gene Products, env / Q000502:physiology; D006801:Humans; D011257:Pregnancy Proteins / Q000502:physiology; D014327:Trophoblasts / Q000473:pathology*
chemical_list: C518353:ERVFRD-1 protein, human; D015686:Gene Products, env; D011257:Pregnancy Proteins; C405335:syncytin