Department of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians-Universität Munich, Munich, Germany.
Biomedical Center (BMC), Institute for Cardiovascular Physiology and Pathophysiology, Walter Brendel Center for Experimental Medicine (WBex), Faculty of Medicine, Ludwig-Maximilians-Universität Munich, Munich, Germany.
Biol Reprod. 2023 Apr 11;108(4):564-574. doi: 10.1093/biolre/ioad007.
Cell surface carbohydrate antigens sialyl Lewis X (sLeX) and Lewis Y (LeY) are paramount glycoconjugates and are abundantly expressed in the receptive endometrium. Furthermore, among the important biological functions of both antigens is their role in leukocytes adhesion and extravasation. Interleukin-1 beta (IL-1β) is involved in the process of human embryo implantation and placenta development. Here, we used an in vitro model to investigate whether sLeX and LeY are playing a role in the embryo implantation process mediated by IL-1β. Our results are showing that the expression of cell surface sLeX was enhanced in endometrial RL95-2 cells after exposure to IL-1β. RT-qPCR detection indicated that the transcript level of glycosyltransferase gene fucosyltransferase 3 (FUT3) was significantly elevated and that of FUT4/7 and ST3 beta-galactoside alpha-2,3-sialyltransferase 3/4 (ST3GAL3/4) were decreased by treatment with IL-1β. Modulatory role of glycosyltransferase FUT3 on sLeX biosynthesis was determined by FUT3 siRNA transfection in RL95-2 cells. Results showed that the expression level of sLeX was suppressed, but no change was observed in regard to LeY. Moreover, IL-1β promoted the HTR-8/SVneo trophoblast spheroids attachment to the RL95-2 endometrial monolayer, which was partially blocked by anti-sLeX antibody and FUT3 knockdown. Gene expression analysis of the RNA-seq transcriptome data from human secretory endometrium demonstrated a significantly higher level of FUT3 in the mid-secretory phase compared to the early secretory phase, which was correlated with the expression of IL1B. In summary, the inflammatory microenvironment at the fetomaternal interface can regulate the glycosylation pattern of endometrial cells at the time of implantation. SLeX can be significantly induced by IL-1β via increasing FUT3 expression, which facilitates the trophoblast adhesion during embryo implantation.
细胞表面碳水化合物抗原唾液酸化路易斯 X（sLeX）和路易斯 Y（LeY）是最重要的糖缀合物，在接受性子宫内膜中大量表达。此外，这两种抗原的重要生物学功能之一是在白细胞黏附和渗出中的作用。白细胞介素-1β（IL-1β）参与人类胚胎着床和胎盘发育过程。在这里，我们使用体外模型研究了 sLeX 和 LeY 是否在 IL-1β介导的胚胎着床过程中发挥作用。我们的结果表明，在暴露于 IL-1β后，子宫内膜 RL95-2 细胞表面 sLeX 的表达增强。RT-qPCR 检测表明，糖基转移酶基因岩藻糖基转移酶 3（FUT3）的转录水平显著升高，而 FUT4/7 和 ST3 β-半乳糖苷 α-2,3-唾液酸转移酶 3/4（ST3GAL3/4）的转录水平降低。通过用 IL-1β处理 RL95-2 细胞，确定了糖基转移酶 FUT3 对 sLeX 生物合成的调节作用。结果表明，sLeX 的表达水平受到抑制，但 LeY 没有变化。此外，IL-1β促进 HTR-8/SVneo 滋养层球体附着到 RL95-2 子宫内膜单层，这被抗 sLeX 抗体和 FUT3 敲低部分阻断。来自人类分泌期子宫内膜的 RNA-seq 转录组数据的基因表达分析表明，与早期分泌期相比，中分泌期 FUT3 的水平显著升高，这与 IL1B 的表达相关。总之，在胚胎着床时，胎母体界面的炎症微环境可以调节子宫内膜细胞的糖基化模式。SLeX 可以通过增加 FUT3 的表达被 IL-1β 显著诱导，从而促进胚胎着床过程中的滋养层黏附。
