{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:18:35Z","timestamp":1792444715822,"version":"4.5.0"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"29","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,7,21]]},"abstract":"<jats:p>\n                    In most mammalian species, a key process of placenta development is the fusion of trophoblast cells into a highly specialized, multinucleated syncytiotrophoblast layer, through which most of the maternofetal exchanges take place. Little is known about this process, despite the recent identification of 2 pairs of envelope genes of retroviral origin, independently acquired by the human (\n                    <jats:italic>syncytin-1<\/jats:italic>\n                    and\n                    <jats:italic>syncytin-2<\/jats:italic>\n                    ) and mouse (\n                    <jats:italic>syncytin-A<\/jats:italic>\n                    and\n                    <jats:italic>syncytin-B<\/jats:italic>\n                    ) genomes, specifically expressed in the placenta, and with in vitro cell\u2013cell fusion activity. By generating knockout mice, we show here that homozygous\n                    <jats:italic>syncytin-A<\/jats:italic>\n                    null mouse embryos die in utero between 11.5 and 13.5 days of gestation. Refined cellular and subcellular analyses of the\n                    <jats:italic>syncytin-A<\/jats:italic>\n                    -deficient placentae disclose specific disruption of the architecture of the syncytiotrophoblast-containing labyrinth, with the trophoblast cells failing to fuse into an interhemal syncytial layer. Lack of\n                    <jats:italic>syncytin-A<\/jats:italic>\n                    -mediated trophoblast cell fusion is associated with cell overexpansion at the expense of fetal blood vessel spaces and with apoptosis, adding to the observed maternofetal interface structural defects to provoke decreased vascularization, inhibition of placental transport, and fetal growth retardation, ultimately resulting in death of the embryo. These results demonstrate that\n                    <jats:italic>syncytin-A<\/jats:italic>\n                    is essential for trophoblast cell differentiation and syncytiotrophoblast morphogenesis during placenta development, and they provide evidence that genes captured from ancestral retroviruses have been pivotal in the acquisition of new, important functions in mammalian evolution.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0902925106","type":"journal-article","created":{"date-parts":[[2009,6,29]],"date-time":"2009-06-29T21:42:29Z","timestamp":1246311749000},"page":"12127-12132","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":356,"title":["Syncytin-A knockout mice demonstrate the critical role in placentation of a fusogenic, endogenous retrovirus-derived, envelope gene"],"prefix":"10.1073","volume":"106","author":[{"given":"Anne","family":"Dupressoir","sequence":"first","affiliation":[{"name":"Unit\u00e9 des R\u00e9trovirus Endog\u00e8nes et El\u00e9ments R\u00e9tro\u00efdes des Eucaryotes Sup\u00e9rieurs, Unit\u00e9 Mixte de Recherche 8122, Centre National de la Recherche Scientifique, Institut Gustave Roussy, 94805 Villejuif, and Universit\u00e9 Paris-Sud, 91405 Orsay, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Vernochet","sequence":"additional","affiliation":[{"name":"Unit\u00e9 des R\u00e9trovirus Endog\u00e8nes et El\u00e9ments R\u00e9tro\u00efdes des Eucaryotes Sup\u00e9rieurs, Unit\u00e9 Mixte de Recherche 8122, Centre National de la Recherche Scientifique, Institut Gustave Roussy, 94805 Villejuif, and Universit\u00e9 Paris-Sud, 91405 Orsay, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Bawa","sequence":"additional","affiliation":[{"name":"Vectorologie et Transfert de G\u00e8nes, Unit\u00e9 Mixte de Recherche 8121, Institut Gustave Roussy, 94805 Villejuif, and Universit\u00e9 Paris-Sud, 91405 Orsay, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Harper","sequence":"additional","affiliation":[{"name":"Laboratoire de R\u00e9plication de l'ADN et Ultrastructure du Noyau, Formation de Recherche en Evolution 2937, Institut Andr\u00e9 Lwoff, 94801 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9rard","family":"Pierron","sequence":"additional","affiliation":[{"name":"Laboratoire de R\u00e9plication de l'ADN et Ultrastructure du Noyau, Formation de Recherche en Evolution 2937, Institut Andr\u00e9 Lwoff, 94801 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paule","family":"Opolon","sequence":"additional","affiliation":[{"name":"Vectorologie et Transfert de G\u00e8nes, Unit\u00e9 Mixte de Recherche 8121, Institut Gustave Roussy, 94805 Villejuif, and Universit\u00e9 Paris-Sud, 91405 Orsay, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Heidmann","sequence":"additional","affiliation":[{"name":"Unit\u00e9 des R\u00e9trovirus Endog\u00e8nes et El\u00e9ments R\u00e9tro\u00efdes des Eucaryotes Sup\u00e9rieurs, Unit\u00e9 Mixte de Recherche 8122, Centre National de la Recherche Scientifique, Institut Gustave Roussy, 94805 Villejuif, and Universit\u00e9 Paris-Sud, 91405 Orsay, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,7,21]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7696(01)05005-7"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1053\/plac.2001.0738"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2004.05.014"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00001.2005"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1211275"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-2-46"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1024455415443"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1159\/000084964"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/35001608"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.7.3321-3329.2000"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2132646100"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406509102"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.048470"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.13.5687-5698.2005"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.2.12a.1639"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend-2-6-579"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.138.9.5369"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5396.2072"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/35003601"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00224265"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.020099"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1699"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2007.51"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603836103"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.24.10979-10988.2005"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/77076"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.7.2466-2474.2000"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.25.14920"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-82-7-1597"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707873105"},{"key":"e_1_3_3_31_2","first-page":"3700","article-title":"Defect of villous cytotrophoblast differentiation into syncytiotrophoblast in Down's syndrome","volume":"85","author":"Frendo JL","year":"2000","unstructured":"JL Frendo, et al., Defect of villous cytotrophoblast differentiation into syncytiotrophoblast in Down's syndrome. 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