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The placenta is an indispensable chimeric organ that supports mammalian embryonic development. Using a mouse model of genetic inactivation of PI3K p110\u03b4 (p110\u03b4<jats:sup>D910A\/D910A<\/jats:sup>), we show that fetuses carried by p110\u03b4<jats:sup>D910A\/D910A<\/jats:sup> females were growth retarded and showed increased mortality in utero mainly during placentation. The placentas in p110\u03b4<jats:sup>D910A\/D910A<\/jats:sup> females were anomalously anemic, exhibited thinner spongiotrophoblast layer and looser labyrinth zone, which indicate defective placental vasculogenesis. In addition, p110\u03b4 was detected in primary trophoblast giant cells (P-TGC) at early placentation. Maternal PI3K p110\u03b4 inactivation affected normal TGCs generation and expansion, impeded the branching of chorioallantoic placenta but enhanced the expression of matrix metalloproteinases (MMP-2, MMP-12). Poor vasculature support for the developing fetoplacental unit resulted in fetal death or gross growth retardation. These data, taken together, provide the first <jats:italic>in vivo<\/jats:italic> evidence that p110\u03b4 may play an important role in placental vascularization through manipulating trophoblast giant cell.<\/jats:p>","DOI":"10.1038\/srep28201","type":"journal-article","created":{"date-parts":[[2016,6,16]],"date-time":"2016-06-16T05:55:56Z","timestamp":1466056556000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Phosphoinositide 3-Kinase (PI3K) Subunit p110\u03b4 Is Essential for Trophoblast Cell Differentiation and Placental Development in Mouse"],"prefix":"10.1038","volume":"6","author":[{"given":"Xiwen","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangchao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyun","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingli","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quliang","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiang","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun-Wei","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,6,16]]},"reference":[{"key":"BFsrep28201_CR1","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1126\/science.7985020","volume":"266","author":"JC Cross","year":"1994","unstructured":"Cross, J. 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