Abstract：
Interferon-τ (IFN-τ) participates in the establishment of endometrial receptivity in ruminants. However, the precise mechanisms by which IFN-τ establishes bovine endometrial receptivity remain largely unknown. Interferon regulatory factor 1 (IRF1) is a classical interferon-stimulated gene (ISG) induced by type I interferon, including IFN-τ. Leukemia inhibitory factor receptor (LIFR) is a transmembrane receptor for leukemia inhibitory factor (LIF), which is a key factor in regulating embryo implantation in mammals. This study aimed to investigate the roles of IRF1 and LIFR in the regulation of bovine endometrial receptivity by IFN-τ. In vivo, we found IRF1 and LIFR were upregulated in the bovine endometrial luminal epithelium on Day 18 of pregnancy compared to Day 18 of the estrous cycle. In vitro, IFN-τ could upregulate IRF1, LIFR, and endometrial receptivity markers (LIF, HOXA10, ITGAV, and ITGB3) expression, downregulate E-cadherin expression and reduce the quantity of microvilli of bovine endometrial epithelial cells (bEECs). Overexpression of IRF1 had similar effects to IFN-τ on endometrial receptivity, and interference of LIFR could block these effects, suggesting the positive effects of IRF1 on endometrial receptivity were mediated by LIFR. Dual luciferase reporter assay verified that IRF1 could transactivate LIFR transcription by binding to its promoter. In conclusion, IFN-τ can induce IRF1 expression in bovine endometrial epithelial cells, and IRF1 upregulates LIFR expression by binding to LIFR promoter, contributing to the enhancement of bovine endometrial receptivity.
摘要：
干扰素-τ（IFN-τ）参与反刍动物子宫内膜容受性的建立。然而,IFN-τ建立牛子宫内膜容受性的确切机制仍然未知。干扰素调节因子1（IRF1）是由I型干扰素诱导的经典干扰素刺激基因（ISG），包括IFN-τ。白血病抑制因子受体(LIFR)是白血病抑制因子(LIF)的跨膜受体,这是调节哺乳动物胚胎植入的关键因素。本研究旨在探讨IRF1和LIFR在IFN-τ调控牛子宫内膜容受性中的作用。在体内,我们发现,与发情周期的第18天相比,在妊娠第18天牛子宫内膜腔上皮中IRF1和LIFR上调.体外，IFN-τ可以上调IRF1、LIFR、和子宫内膜容受性标志物(LIF，HOXA10,ITGAV,和ITGB3)表达式，下调E-cadherin的表达并减少牛子宫内膜上皮细胞（bEECs）的微绒毛数量。IRF1过表达对子宫内膜容受性的影响与IFN-τ相似，LIFR的干扰可以阻止这些影响，提示IRF1对子宫内膜容受性的积极影响是由LIFR介导的。双荧光素酶报告基因测定证实IRF1可以通过与其启动子结合来反式激活LIFR转录。总之,IFN-τ可诱导牛子宫内膜上皮细胞IRF1表达,IRF1通过结合LIFR启动子上调LIFR表达，有助于增强牛子宫内膜的容受性。
