Institute of Life Sciences, Chongqing Medical University, Chongqing, China.
Experimental Research Center, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Mol Reprod Dev. 2019 Jun;86(6):696-713. doi: 10.1002/mrd.23148. Epub 2019 Apr 23.
Prolactin family 7, subfamily d, member 1 (Prl7d1), a member of the expanding prolactin family, is mainly expressed in the placental junctional zone (including trophoblast giant cells and spongiotrophoblast cells) with peak expression observed at 12 days postcoitum (dpc) in mice. 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 Prl7d1 in mice and demonstrated that its absence results in reduced litter size and fertility. Histologically, Prl7d1 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 Prl7d1-null mice displayed a thickened decidual spiral artery. Notably, these negative effects were more pronounced in male fetuses. Further RNA-sequencing analysis showed that Prl7d1 deletion results in significant differences in the placental transcriptome profile between the two sexes of fetuses. Together, this study demonstrates that Prl7d1 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 Prl7d1 in the placenta is regulated in a fetal sex-specific manner.
泌乳素家族 7，亚家族 d，成员 1（Prl7d1），是不断扩展的泌乳素家族的成员，主要在胎盘结合区（包括滋养细胞巨细胞和海绵滋养层细胞）表达，在小鼠中于妊娠后 12 天（dpc）达到表达高峰。先前的研究表明，PRL7D1 是体外血管生成的关键介质；然而，其在体内胎盘发育中的生理作用尚未得到表征。为了解决这个问题，我们在小鼠中敲除了 Prl7d1，并证明其缺失导致胎仔数量和生育力减少。组织学上，Prl7d1 突变体在 12.5 dpc 时表现出明显的胎盘异常，包括绒毛层比例减少，结合区蜕膜自然杀伤细胞、糖原滋养层细胞和滋养细胞巨细胞显著增加。此外，Prl7d1 缺失小鼠的胎盘螺旋动脉增厚。值得注意的是，这些负面影响在雄性胎儿中更为明显。进一步的 RNA-seq 分析表明，Prl7d1 缺失导致两种性别胎儿胎盘转录组图谱存在显著差异。总之，这项研究表明，Prl7d1 在蜕膜中具有抗血管生成特性，并抑制结合区的发育，这可能改变胎盘支持最佳胎儿生长的功能能力。此外，值得注意的是，Prl7d1 在胎盘中的作用以胎儿性别特异性的方式进行调节。
