Chen Yue, Zhang Hui, Han Fang, Yue Lei, Qiao Chunxiao, Zhang Yao, Dou Peng, Liu Weizhe, Li Yu
School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
J Cell Physiol. 2018 Mar;233(3):2257-2269. doi: 10.1002/jcp.26098. Epub 2017 Aug 17.
The placenta is a remarkable organ, it serves as the interface between the mother and the fetus. Proper invasion of trophoblast cells is required for a successful pregnancy. Previous studies have found that the adhesion molecule integrin β4 plays important roles during trophoblast cell invasion. Here, we found that the overall birth rate of the MARVELD1 knockout mouse is much lower than that of the wild-type mouse (p < 0.001). In E18.5 MARVELD1 knockout mice, we observed an over-invasion of trophoblast cells, and indeed, the pregnant mice had a partial placenta accreta phenotype. The HTR8/SVneo cell line was used as an in vitro model to elucidate the underlying mechanisms of MARVELD1-mediated trophoblast invasion. We detected a diminished expression of integrin β4 upon the downregulation of MARVELD1 and enhanced migrate and invasive abilities of trophoblast cells both in vivo and in vitro. The integrin β4 rescue assay also supported the results. In conclusion, this study found that MARVELD1 mediated the invasion of trophoblast cells via regulating the expression of integrin β4 during placenta development.
胎盘是一个非凡的器官，它充当母亲与胎儿之间的界面。滋养层细胞的适当侵入是成功怀孕所必需的。先前的研究发现，黏附分子整合素β4在滋养层细胞侵入过程中起重要作用。在此，我们发现MARVELD1基因敲除小鼠的总体出生率远低于野生型小鼠（p < 0.001）。在E18.5期的MARVELD1基因敲除小鼠中，我们观察到滋养层细胞过度侵入，实际上，怀孕小鼠具有部分胎盘植入表型。HTR8/SVneo细胞系用作体外模型以阐明MARVELD1介导的滋养层侵入的潜在机制。在MARVELD1下调后，我们检测到整合素β4的表达减少，并且在体内和体外滋养层细胞的迁移和侵入能力均增强。整合素β4拯救试验也支持了这些结果。总之，本研究发现，在胎盘发育过程中，MARVELD1通过调节整合素β4的表达介导滋养层细胞的侵入。
