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P\u2010glycoprotein (P\u2010gp encoded by <jats:italic><jats:styled-content style=\"fixed-case\">ABCB<\/jats:styled-content>1<\/jats:italic>) is an <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>\u2010binding cassette transporter present in the syncytiotrophoblast layer of the placenta where it acts as a molecular sieve. In this study, we show that P\u2010gp is also expressed in the proliferating cytotrophoblast (<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>), the syncytiotrophoblast (<jats:styled-content style=\"fixed-case\">ST<\/jats:styled-content>) and the extravillous trophoblast (<jats:styled-content style=\"fixed-case\">EVT<\/jats:styled-content>), suggesting our hypothesis of a functional role for P\u2010gp in placental development. Silencing of <jats:italic><jats:styled-content style=\"fixed-case\">ABCB<\/jats:styled-content>1,<\/jats:italic> via si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> duplex, results in dramatically reduced invasion and migration, and increased tube formation and fusion in the <jats:styled-content style=\"fixed-case\">EVT<\/jats:styled-content>\u2010like <jats:styled-content style=\"fixed-case\">HTR<\/jats:styled-content>8\/<jats:styled-content style=\"fixed-case\">SV<\/jats:styled-content><jats:sub>neo<\/jats:sub> cell line. In both <jats:styled-content style=\"fixed-case\">EVT<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> explant differentiation experiments, silencing of <jats:italic><jats:styled-content style=\"fixed-case\">ABCB<\/jats:styled-content>1<\/jats:italic> leads to induction of the fusion markers human hCG, ERVW\u20101 and GJA1 and terminal differentiation of both trophoblast subtypes. Moreover, P\u2010gp protein levels are decreased in both the villous and the <jats:styled-content style=\"fixed-case\">EVT<\/jats:styled-content> of severe early\u2010onset pre\u2010eclamptic placentas. We conclude that, in addition to its role as a syncytial transporter, P\u2010gp is a key factor in the maintenance of both <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">EVT<\/jats:styled-content> lineages and that its decrease in severe pre\u2010eclampsia may contribute to the syncytial and <jats:styled-content style=\"fixed-case\">EVT<\/jats:styled-content> placental pathologies associated with this disease.<\/jats:p>","DOI":"10.1111\/jcmm.13810","type":"journal-article","created":{"date-parts":[[2018,9,6]],"date-time":"2018-09-06T04:11:50Z","timestamp":1536207110000},"page":"5378-5393","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["P\u2010Glycoprotein (P\u2010gp)\/<scp>ABCB<\/scp>1 plays a functional role in extravillous trophoblast (<scp>EVT<\/scp>) invasion and is decreased in the pre\u2010eclamptic placenta"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4146-099X","authenticated-orcid":false,"given":"Caroline E.","family":"Dunk","sequence":"first","affiliation":[{"name":"Lunenfeld Tanenbaum Research Institute Sinai Health System Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane J.","family":"Pappas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics McGill University Montreal Canada"},{"name":"Department of Physiology University of Toronto Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phetcharawan","family":"Lye","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Toronto Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Kibschull","sequence":"additional","affiliation":[{"name":"Lunenfeld Tanenbaum Research Institute Sinai Health System Toronto 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