Laboratory of Neuroimmunology and Developmental Origins of Disease (NIDOD), University Medical Center Utrecht, Utrecht 3584 EA, The Netherlands.
Hum Reprod Update. 2013 Sep-Oct;19(5):542-57. doi: 10.1093/humupd/dmt025. Epub 2013 Jul 4.
BACKGROUND Mechanisms underlying early reproductive loss in the human are beginning to be elucidated. The migratory and invasive capacity of human endometrial stromal cells (ESCs) is increasingly recognized to contribute to the intense tissue remodelling associated with embryo implantation, trophoblast invasion and endometrial regeneration. In this review, we examine the signals and mechanisms that control ESC migration and invasion and assess how deregulation of these cell functions contributes to common reproductive disorders. METHODS The PubMed database was searched for publications on motility and invasiveness of human ESCs in normal endometrial function and in reproductive disorders including implantation failure, recurrent pregnancy loss (RPL), endometriosis and adenomyosis, covering the period 2000-2012. RESULTS Increasing evidence suggests that implantation failure and RPL involve abnormal migratory responses of decidualizing ESCs to embryo and trophoblast signals. Numerous reports indicate that endometriosis, as well as adenomyosis, is associated with increased basal and stimulated invasiveness of ESCs and their progenitor cells, suggesting a link between a heightened menstrual repair response and the formation of ectopic implants. Migration and invasiveness of ESCs are controlled by a complex array of hormones, growth factors, chemokines and inflammatory mediators, and involve signalling through Rho GTPases, phosphatidylinositol-3-kinase and mitogen-activated protein kinase pathways. CONCLUSIONS Novel concepts are extending our understanding of the key functions of ESCs in effecting tissue repair imposed by cyclic menstruation and parturition. Migration of decidualizing ESCs also serves to support blastocyst implantation and embryo selection through discriminate motile responses directed by embryo quality. Targeting regulatory molecules holds promise for developing new strategies for the treatment of reproductive disorders such as endometriosis and recurrent miscarriage; and harnessing the migratory capacity of progenitor mesenchymal stem cells in the endometrium may offer new opportunities in regenerative medicine.
人类早期生殖损失的机制开始被阐明。越来越多的人认识到，人类子宫内膜基质细胞（ESCs）的迁移和侵袭能力有助于与胚胎着床、滋养层浸润和子宫内膜再生相关的强烈组织重塑。在这篇综述中，我们检查了控制 ESC 迁移和侵袭的信号和机制，并评估了这些细胞功能的失调如何导致常见的生殖障碍。
在正常子宫内膜功能和生殖障碍（包括着床失败、复发性妊娠丢失（RPL）、子宫内膜异位症和子宫腺肌病）中，搜索了 2000 年至 2012 年期间关于人 ESC 迁移和侵袭的文献数据库。
越来越多的证据表明，着床失败和 RPL 涉及到胚胎和滋养层信号对蜕膜化 ESC 异常迁移反应。许多报道表明，子宫内膜异位症以及子宫腺肌病与 ESC 及其祖细胞的基础和刺激侵袭性增加有关，这表明月经修复反应增强与异位植入物的形成之间存在联系。ESC 的迁移和侵袭受到复杂的激素、生长因子、趋化因子和炎症介质的控制，并涉及 Rho GTPases、PI3K 和 MAPK 信号通路的信号转导。
新概念扩展了我们对 ESC 在周期性月经和分娩引起的组织修复中的关键功能的理解。蜕膜化 ESC 的迁移也通过胚胎质量指导的有区别的运动反应来支持胚泡着床和胚胎选择。靶向调节分子为治疗子宫内膜异位症和复发性流产等生殖障碍提供了新的策略，而利用子宫内膜中祖性质间充质干细胞的迁移能力可能为再生医学提供新的机会。
