Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan.
Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo 160-0023, Japan.
Int J Mol Sci. 2021 Sep 29;22(19):10505. doi: 10.3390/ijms221910505.
Previous in vitro studies have suggested that calreticulin (CALR), which is responsible for the folding and quality control of glycoproteins, may be associated with decidualization. However, its precise role in regulating decidualization has not been explored in vivo. Here, we used pregnant rat models to examine endometrial CALR expression during the peri-implantation period. We also examined whether polypectomy, a procedure that could ameliorate infertility, alters the endometrial expression levels of CALR and several implantation factors in women diagnosed as infertile. In rats, uterine CALR was expressed at a high level at the implantation site, and a marked increase in CALR expression was observed in decidual cells of normal pregnancy. In addition, endometrial CALR expression was enhanced by either administration of estradiol-17β in the delayed implantation rat model or the artificial induction of decidualization in the pseudopregnant rat. In cultured stromal cells, siRNA-mediated silencing of CALR inhibited the decidual stimulus-induced expression of prolactin, decidual/trophoblast prolactin-related protein, and connexin 43. In humans, the endometrial expression levels of the mRNAs encoding CALR and the implantation-related factor insulin-like growth factor binding protein (IGFBP)-7 tended to increase after polypectomy. The strongest positive correlation between expression levels before polypectomy was observed for IGFBP-7 and CALR, and the strength of this correlation increased after the surgery. Thus, endometrial CALR may play a role in the formation of decidua, and the polypectomy of infertile patients may result in the co-operative expression of endometrial factors, including CALR, that could enhance endometrial receptivity.
先前的体外研究表明，钙网蛋白（CALR）负责糖蛋白的折叠和质量控制，可能与蜕膜化有关。然而，其在体内调节蜕膜化的确切作用尚未被探索。在这里，我们使用怀孕大鼠模型来研究着床期子宫内膜 CALR 的表达。我们还检查了息肉切除术（一种可以改善不孕的程序）是否改变了诊断为不孕的女性的子宫内膜 CALR 表达水平和几种着床因子。在大鼠中，子宫 CALR 在着床部位表达水平较高，在正常妊娠的蜕膜细胞中观察到 CALR 表达明显增加。此外，子宫内膜雌二醇-17β给药或假孕大鼠蜕膜化的人工诱导增强了子宫内膜 CALR 的表达。在培养的基质细胞中，CALR 的 siRNA 介导的沉默抑制了催乳素、蜕膜/滋养层催乳素相关蛋白和连接蛋白 43 的蜕膜刺激诱导表达。在人类中，息肉切除术后，编码 CALR 和着床相关因子胰岛素样生长因子结合蛋白（IGFBP）-7 的 mRNA 的子宫内膜表达水平趋于增加。在息肉切除术前，IGFBP-7 和 CALR 的表达水平之间观察到最强的正相关，手术后这种相关性增强。因此，子宫内膜 CALR 可能在蜕膜形成中发挥作用，不孕患者的息肉切除术可能导致包括 CALR 在内的子宫内膜因子的协同表达，从而增强子宫内膜的接受性。
