Rictor/mTORC2 is involved in endometrial receptivity by regulating epithelial remodeling
Rictor/mTORC2 is involved in endometrial receptivity by regulating epithelial remodeling
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Rictor/mTORC2 通过调节上皮重塑参与子宫内膜容受性
DOI：
10.1096/fj.202100529rr
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发表时间：
2021
期刊：
影响因子：
4.8
通讯作者：
耿艳清
中科院分区：
文献类型：
--
作者：
张悦;杜欣蔓;陈雪梅;汤红宇;周勤;何俊琳;丁裕斌;王应雄;刘学庆;耿艳清
成功的胚胎植入需要功能良好的子宫内膜腔上皮细胞来建立子宫容受性。子宫容受性不足是造成人类约三分之二着床失败的原因。然而，管理这一功能过程的调节机制在很大程度上仍未得到探索。先前的研究表明，小鼠上皮细胞中mTORC 2的主要成员Rictor的表达在妊娠第四天（D4）增加。在这里，我们提供了第一份报告的参与Rictor在调节子宫内膜容受性。使用孕酮受体cre（PRcre）小鼠模型在小鼠子宫内膜中有条件地消融Rictor。Rictor的缺失分别通过介导Rac-1/PAK 1（pPAK 1）/ERM（pERM）和Sgk 1/pSgk 1信号传导改变了子宫内膜细胞的极性重塑和Na+通道蛋白，最终导致生育力受损。在不孕症患者子宫内膜中，Rictor的表达发生改变，沿着上皮细胞的形态学改变和Na+通道蛋白的表达。我们的研究结果表明，Rictor是至关重要的建立在小鼠和人类的子宫容受性。本研究可能有助于完善子宫内膜容受性的分子调控网络，为不孕症的诊断和治疗提供新的策略。
Successful embryo implantation requires well‐functioning endometrial luminal epithelial cells to establish uterine receptivity. Inadequate uterine receptivity is responsible for approximately two thirds of implantation failures in humans. However, the regulatory mechanism governing this functional process remains largely unexplored. A previous study revealed that the expression of Rictor, the main member of mTORC2, in mouse epithelial cells is increased on the fourth day of gestation (D4). Here, we provide the first report of the involvement of Rictor in the regulation of endometrial receptivity. Rictor was conditionally ablated in the mouse endometrium using a progesterone receptor cre (PRcre) mouse model. Loss of Rictor altered polarity remodeling and the Na+channel protein of endometrial cells by mediating Rac‐1/PAK1(pPAK1)/ERM(pERM) and Sgk1/pSgk1 signaling, respectively, ultimately resulting in impaired fertility. In the endometrium of women with infertility, the expression of Rictor was changed, along with the morphological transformation and Na+channel protein of epithelial cells. Our findings demonstrate that Rictor is crucial for the establishment of uterine receptivity in both mice and humans. The present study may help improve the molecular regulatory network of endometrial receptivity and provide new diagnostic and treatment strategies for infertility.