Joint International Research Laboratory of Reproduction & Development, School of Public Health and Management, Chongqing Medical University, Chongqing, P.R. China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
FASEB J. 2021 Jul;35(7):e21731. doi: 10.1096/fj.202100529RR.
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 (PR ) 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.
成功的胚胎着床需要功能良好的子宫内膜腔上皮细胞来建立子宫容受性。大约三分之二的人类着床失败是由于子宫容受性不足所致。然而，调控这一功能过程的机制在很大程度上仍未被探索。先前的研究表明，mTORC2 的主要成员 Rictor 在妊娠第 4 天（D4）时在小鼠上皮细胞中的表达增加。在这里，我们首次报道了 Rictor 参与调节子宫内膜容受性。我们使用孕激素受体 cre（PR ）小鼠模型对小鼠子宫内膜中的 Rictor 进行条件性敲除。Rictor 的缺失通过分别介导 Rac-1/PAK1(pPAK1)/ERM(pERM) 和 Sgk1/pSgk1 信号通路改变了子宫内膜细胞的极性重塑和 Na 通道蛋白，最终导致生育能力受损。在不孕女性的子宫内膜中，Rictor 的表达发生改变，同时上皮细胞的形态发生变化和 Na 通道蛋白也发生改变。我们的研究结果表明，Rictor 对小鼠和人类子宫容受性的建立至关重要。本研究可能有助于改善子宫内膜容受性的分子调控网络，并为不孕提供新的诊断和治疗策略。
