CONICET, Universidad de Buenos Aires, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales IQUIBICEN, Buenos Aires, Argentina.
Reproduction. 2020 Apr;159(4):R203-R211. doi: 10.1530/REP-19-0391.
Decidualization denotes the reprogramming of endometrial stromal cells that includes the secretion of different mediators like cytokines, chemokines, and the selective recruitment of immune cells. This physiological process involves changes in the secretome of the endometrial stromal cells leading to the production of immunomodulatory factors. The increased amount of protein secretion is associated with a physiological endoplasmic reticulum (ER) stress and the resulting unfolded protein response (UPR), allowing the expansion of ER and the machinery to assist the protein folding. Notably, the signaling pathways involved in the ER stress and the UPR are interconnected with the onset of a sterile inflammatory response, as well as with angiogenesis. Both of these processes have a key role in decidualization and placentation, therefore, alterations in them could lead to pregnancy complications. In this review, we will discuss how the induction of ER stress and the UPR processes that accompanies the decidualization are associated with embryo implantation and whether they might condition pregnancy outcome. The ER stress activates/triggers sensing proteins which, among others, induces kinase/RNAse-TXNIP expression, activating the NLRP3 inflammasome. This multiprotein system allows caspase-1 activation, which catalyzes the cleavage of the inactive IL-1β proform toward the mature secretory form, with pro-implantatory effects. However, the sterile inflammatory response should be later controlled in favor of a tolerogenic microenvironment to sustain pregnancy. In accordance, alterations of the ER stress and UPR processes can be reflected in recurrent implantation failures (RIF), recurrent pregnancy loss (RPL), or complications associated with deficient placentation, such as preeclampsia (PE).
蜕膜化是指子宫内膜基质细胞的重编程，包括细胞因子、趋化因子等不同介质的分泌，以及免疫细胞的选择性募集。这个生理过程涉及到子宫内膜基质细胞分泌组的变化，导致免疫调节因子的产生。蛋白分泌量的增加与生理性内质网（ER）应激和随之产生的未折叠蛋白反应（UPR）有关，这允许 ER 的扩张和协助蛋白折叠的机制。值得注意的是，涉及 ER 应激和 UPR 的信号通路与无菌性炎症反应以及血管生成的发生相互关联。这两个过程在蜕膜化和胎盘形成中都起着关键作用，因此，它们的改变可能导致妊娠并发症。在这篇综述中，我们将讨论伴随蜕膜化的 ER 应激和 UPR 过程的诱导如何与胚胎着床相关，以及它们是否可能影响妊娠结局。ER 应激激活/触发感应蛋白，其中包括诱导激酶/RNAse-TXNIP 的表达，激活 NLRP3 炎性小体。这个多蛋白系统允许半胱天冬酶-1 的激活，其催化无活性的 IL-1β 前体向成熟分泌形式的切割，具有促进着床的作用。然而，无菌性炎症反应应该随后得到控制，以有利于耐受的微环境来维持妊娠。相应地，ER 应激和 UPR 过程的改变可以反映在反复着床失败（RIF）、反复妊娠丢失（RPL）或与胎盘形成不足相关的并发症中，如子痫前期（PE）。
