Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, School of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Int J Mol Sci. 2023 Oct 17;24(20):15271. doi: 10.3390/ijms242015271.
Crucial roles in embryo implantation and placentation in humans include the invasion of the maternal decidua by extravillous trophoblasts and the motile behavior of decidual endometrial stromal cells. The effects of the epidermal growth factor (EGF) and GnRH-II in the endometrium take part in early pregnancy. In the present study, we demonstrated the coaction of EGF- and GnRH-II-promoted motility of human decidual endometrial stromal cells, indicating the possible roles of EGF and GnRH-II in embryo implantation and early pregnancy. After obtaining informed consent, we obtained human decidual endometrial stromal cells from decidual tissues from normal pregnancies at 6 to 12 weeks of gestation in healthy women undergoing suction dilation and curettage. Cell motility was evaluated with invasion and migration assays. The mechanisms of EGF and GnRH-II were performed using real-time PCR and immunoblot analysis. The results showed that human decidual tissue and stromal cells expressed the EGF and GnRH-I receptors. GnRH-II-mediated cell motility was enhanced by EGF and was suppressed by the knockdown of the endogenous GnRH-I receptor and EGF receptor with siRNA, revealing that GnRH-II promoted the cell motility of human decidual endometrial stromal cells through the GnRH-I receptor and the activation of Twist and N-cadherin signaling. This new concept regarding the coaction of EGF- and GnRH-promoted cell motility suggests that EGF and GnRH-II potentially affect embryo implantation and the decidual programming of human pregnancy.
在人类胚胎植入和胎盘形成中，细胞外滋养层侵入母体蜕膜和蜕膜子宫内膜基质细胞的迁移运动起着至关重要的作用。表皮生长因子（EGF）和 GnRH-II 对子宫内膜的影响参与了早期妊娠。在本研究中，我们证明了 EGF 和 GnRH-II 促进人蜕膜子宫内膜基质细胞运动的协同作用，表明 EGF 和 GnRH-II 在胚胎植入和早期妊娠中可能发挥作用。在获得知情同意后，我们从 6 至 12 孕周正常妊娠的健康妇女行吸宫和刮宫术时获取的蜕膜组织中分离得到人蜕膜子宫内膜基质细胞。通过侵袭和迁移实验评估细胞迁移运动。采用实时 PCR 和免疫印迹分析研究 EGF 和 GnRH-II 的作用机制。结果表明，人蜕膜组织和基质细胞表达 EGF 和 GnRH-I 受体。EGF 增强了 GnRH-II 介导的细胞迁移运动，而 siRNA 敲低内源性 GnRH-I 受体和 EGF 受体则抑制了细胞迁移运动，表明 GnRH-II 通过 GnRH-I 受体激活 Twist 和 N-钙黏蛋白信号通路促进人蜕膜子宫内膜基质细胞的迁移运动。EGF 和 GnRH 促进细胞迁移运动的这种协同作用的新概念表明，EGF 和 GnRH-II 可能影响胚胎植入和人类妊娠的蜕膜编程。
