Activation of Toll-like receptor 5 decreases the attachment of human trophoblast cells to endometrial cells in vitro
Activation of Toll-like receptor 5 decreases the attachment of human trophoblast cells to endometrial cells in vitro
复制标题
DOI：
10.1093/humrep/deq185
复制
发表时间：
2010-09-01
影响因子：
6.1
通讯作者：
Fazeli, Alireza
中科院分区：
文献类型：
--
作者：
Aboussahoud, Wedad;Bruce, Chris;Fazeli, Alireza
胚胎在子宫内着床时，滋养细胞附着于子宫内膜上皮，然后侵入。然而，在生命的这一时期，关于用初级人体组织进行实验的伦理问题需要创建体外模型，以了解所涉及的基本机制。toll样受体（TLRs）在防御病原体入侵女性生殖道中起着至关重要的作用。本研究的目的是建立并优化人子宫内膜胚胎相互作用的体外模型，了解TLR5刺激对滋养细胞与子宫内膜细胞附着的影响。利用人端粒酶永生化子宫内膜上皮细胞系（hTERT-EECs）和绒毛膜癌人滋养细胞（JAr细胞），建立了体外人胚胎植入实验。为了研究TLR5刺激对附着的影响，本实验将细菌鞭毛蛋白应用于子宫内膜和滋养细胞。为了阻断TLR5在子宫内膜和滋养细胞中的作用，在鞭毛蛋白处理之前，在细胞上应用TLR5功能阻断抗体。结果表明，JAr球体与hTERT-EECs呈时间和浓度依赖关系。我们的研究结果还表明，鞭毛蛋白处理子宫内膜细胞，抑制JAr球对子宫内膜细胞的附着。应用TLR5功能阻断抗体可明显恢复JAr微球与子宫内膜的附着。这些数据提示了一种新的机制，通过TLR5激活的宫内感染可能导致着床失败。这些数据可能为不孕症的治疗提供新的机会。
Embryo implantation in the uterus involves the trophoblast cells apposing and adhering to, then invading across the epithelium lining of the endometrium. However, ethical concerns regarding experimentation with primary human tissue during this period of life necessitates creation of in vitro models for understanding the basic mechanisms involved. Toll-like receptors (TLRs) play a crucial role in defence against pathogens invading the female reproductive tract. The objective of this study is to establish and optimize an in vitro model for studying human endometrial embryonic interactions and to understand the effect of TLR5 stimulation on the attachment of trophoblast cells to endometrial cells.By using a human telomerase immortalized endometrial epithelial cell line (hTERT-EECs) and choriocarcinoma human trophoblast cells (JAr cells), an in vitro assay of human implantation was established. In order to investigate the impact of TLR5 stimulation on attachment in this assay, bacterial flagellin was applied to the endometrial and trophoblast cells. In order to block TLR5 in the endometrial and trophoblast cells, TLR5 function-blocking antibody was applied to the cells prior to flagellin treatment.The results demonstrated that JAr spheroids attached to hTERT-EECs in a time and concentration-dependent manner. Our results also demonstrated that treatment of endometrial cells with flagellin, suppressed the attachment of JAr spheres to the endometrial cells. Application of TLR5 function-blocking antibody significantly restored the attachment of JAr spheres to the endometrium.These data suggest a novel mechanism by which the presence of intrauterine infection through TLR5 activation may result in implantation failure. These data may provide a new opportunity in the management of infertility cases.