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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Implantation Of The Human Embryo Requiresrac1-dependent Endometrial Stromal Cell Migration
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Implantation Of The Human Embryo Requiresrac1-dependent Endometrial Stromal Cell Migration

机译:人类胚胎的植入需要依赖rac1的子宫内膜基质细胞迁移。

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Failure of the human embryo to implant into the uterine wall during the early stages of pregnancy is a major cause of infertility. Implantation involves embryo apposition and adhesion to the endometrial epithelium followed by penetration through the epithelium and invasion of the embryonic trophoblast through the endometrial stroma. Although gene-knockdown studies have highlighted several molecules that are important for implantation in the mouse, the molecular mechanisms controlling implantation in the human are unknown. Here, we demonstrate in an in vitro model for human implantation that the Rho GTPases Rac1 and RhoA in human endometrial stromal cells modulate invasion of the human embryo through the endometrial stroma. We show that knockdown of Rac1 expression in human endometrial stromal cells inhibits human embryonic trophoblast invasion into stromal cell monolayers, whereas inhibition of RhoA activity promotes embryo invasion. Furthermore, we demonstrate that Rac1 is required for human endometrial stromal cell migration and that the motility of the stromal cells increases at implantation sites. This increased motility correlates with a localized increase in Rad activation and a reciprocal decrease in RacGAPI levels. These results reveal embryo-induced and localized endometrial responses that may govern implantation of the human embryo.
机译:在怀孕的早期阶段,人类胚胎无法植入子宫壁是不孕的主要原因。植入涉及胚胎并置并粘附于子宫内膜上皮,然后穿透上皮和胚胎滋养层通过子宫内膜基质侵入。尽管基因敲低研究强调了几种对小鼠植入至关重要的分子,但控制人类植入的分子机制尚不清楚。在这里,我们在人类植入的体外模型中证明,人类子宫内膜基质细胞中的Rho GTPases Rac1和RhoA可以通过子宫内膜基质调节人类胚胎的侵袭。我们表明敲除人类子宫内膜基质细胞中Rac1表达抑制人类胚胎滋养层细胞侵入基质细胞单层,而抑制RhoA活性则促进胚胎侵袭。此外,我们证明Rac1是人类子宫内膜基质细胞迁移所必需的,并且基质细胞的运动性在植入位点增加。这种增加的运动性与Rad激活的局部增加和RacGAPI水平的倒数降低相关。这些结果揭示了胚胎诱导的和局部的子宫内膜反应,可以控制人类胚胎的植入。

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