School of Biomedical Sciences, Faculty of Medicine and Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia.
Queensland Brain Institute, Faculty of Medicine and Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia.
Sci Rep. 2018 Mar 2;8(1):3961. doi: 10.1038/s41598-018-22040-2.
Fetal growth and survival is dependent on the elaboration and propinquity of the fetal and maternal circulations within the placenta. Central to this is the formation of the interhaemal membrane, a multi-cellular lamina facilitating exchange of oxygen, nutrients and metabolic waste products between the mother and fetus. In rodents, this cellular barrier contains two transporting layers of syncytiotrophoblast, which are multinucleated cells that form by cell-cell fusion. Previously, we reported the expression of the GPI-linked cell surface protein LY6E by the syncytial layer closest to the maternal sinusoids of the mouse placenta (syncytiotrophoblast layer I). LY6E has since been shown to be a putative receptor for the fusogenic protein responsible for fusion of syncytiotrophoblast layer I, Syncytin A. In this report, we demonstrate that LY6E is essential for the normal fusion of syncytiotrophoblast layer I, and for the proper morphogenesis of both fetal and maternal vasculatures within the placenta. Furthermore, specific inactivation of Ly6e in the epiblast, but not in placenta, is compatible with embryonic development, indicating the embryonic lethality reported for Ly6e embryos is most likely placental in origin.
胎儿的生长和存活依赖于胎盘内胎儿和母体循环的精心构建和毗邻。这其中的核心是形成血胎盘屏障，这是一种多细胞层，促进母体和胎儿之间的氧气、营养物质和代谢废物的交换。在啮齿动物中，这个细胞屏障包含两层具有转运功能的合胞滋养层，它们是由细胞融合形成的多核细胞。此前，我们报道了 GPI 连接的细胞表面蛋白 LY6E 在最接近鼠胎盘母体窦的合胞滋养层（合胞滋养层 I 层）中的表达。此后，LY6E 被证明是一种假定的受体，用于融合合胞滋养层 I 层的融合蛋白，即 Syncytin A。在本报告中，我们证明了 LY6E 对于合胞滋养层 I 的正常融合以及胎盘内胎儿和母体血管的正常形态发生是必不可少的。此外，在胚胎外胚层中特异性失活 Ly6e，但不在胎盘，与胚胎发育相容，表明报道的 Ly6e 胚胎的胚胎致死性很可能源于胎盘。
