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Previous studies have shown that PRL7D1 is a key mediator of angiogenesis in vitro; however, its physiological roles in placental development in vivo have not been characterized. To address this issue, we deleted <jats:italic>Prl7d1<\/jats:italic> in mice and demonstrated that its absence results in reduced litter size and fertility. Histologically, <jats:italic>Prl7d1<\/jats:italic> mutants exhibited striking placental abnormalities at 12.5 dpc, including a reduction in the proportion of labyrinth layers and a significant increase in decidual natural killer cells, glycogen trophoblasts, and trophoblast giant cells in the junctional zone. Moreover, placentas from <jats:italic>Prl7d1\u2010<\/jats:italic>null mice displayed a thickened decidual spiral artery. Notably, these negative effects were more pronounced in male fetuses. Further RNA\u2010sequencing analysis showed that <jats:italic>Prl7d1<\/jats:italic> deletion results in significant differences in the placental transcriptome profile between the two sexes of fetuses. Together, this study demonstrates that <jats:italic>Prl7d1<\/jats:italic> possesses antiangiogenic properties in deciduas and inhibits the development of junctional zone, which potentially alters the functional capacity of the placenta to support optimal fetal growth. Moreover, of note, the role of <jats:italic>Prl7d1<\/jats:italic> in the placenta is regulated in a fetal sex\u2010specific manner.<\/jats:p>","DOI":"10.1002\/mrd.23148","type":"journal-article","created":{"date-parts":[[2019,4,23]],"date-time":"2019-04-23T13:00:31Z","timestamp":1556024431000},"page":"696-713","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Deletion of <i>Prl7d1<\/i> causes placental defects at mid\u2010pregnancy in mice"],"prefix":"10.1002","volume":"86","author":[{"given":"Qiong","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Life Sciences Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Hao","sequence":"additional","affiliation":[{"name":"Experimental Research Center, The First Affiliated Hospital Chongqing Medical University Chongqing 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