ST6GALNAC1-mediated sialylation in uterine endometrial epithelium facilitates the epithelium-embryo attachment,Journal of Advanced Research

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ST6GALNAC1-mediated sialylation in uterine endometrial epithelium facilitates the epithelium-embryo attachment
Journal of Advanced Research ( IF 11.4 ) Pub Date : 2024-08-05 , DOI: 10.1016/j.jare.2024.07.021
Xinyue Dong ₁ , Hao Wang ₂ , Jinxuan Cai ₂ , Yichun Wang ₃ , Dezhi Chai ₂ , Zichen Sun ₂ , Jie Chen ₂ , Mengxia Li ₂ , Tianxia Xiao ₂ , Chunhua Shan ₄ , Jian V Zhang ₅ , Ming Yu ₂

Affiliation

Introduction

Embryo implantation requires synergistic interaction between the embryo and the receptive endometrium. Glycoproteins and glycan-binding proteins are involved in endometrium-embryo attachment. Sialyl Tn (sTn), a truncated O-glycan, is catalyzed by ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) and can be detected by specific Sialic-acid-binding immunoglobulin-like lectins (Siglecs). Whether the sTn-Siglecs axis supports embryo implantation remains unknown.

Objectives

This paper aims to study the role of ST6GALNAC1/sTn-Siglecs axis in embryo implantation.

Methods

ST6GALNAC1 and sTn in human endometrium were analyzed by immunohistochemistry. An in vitro implantation model was conducted to evaluate the effects of ST6GALNAC1/sTn on the receptivity of human endometrial AN3CA cells to JAR spheroids. Immunoprecipitation combined with mass spectrometry analysis was carried out to identify the key proteins modified by sTn in endometrial cells. Siglec-6 in human embryos was analyzed by published single-cell RNA sequencing (scRNA-seq) datasets. Protein interaction assay was applied to verify the bond between the Siglec-6 with sTn-modified CD44. St6galnac1 siRNAs and anti-sTn antibodies were injected into the uterine horn of the mouse at the pre-implantation stage to evaluate the role of endometrial St6galnac1/sTn in embryo implantation. Siglec-G in murine embryos was analyzed by immunofluorescence staining. The function of Siglec-G is evidenced by uterine horn injection and protein interaction assay.

Results

Both human and murine endometrium at the receptive stage exhibit higher ST6GALNAC1 and sTn levels compared to the non-receptive stage. Overexpression of ST6GALNAC1 significantly enhanced the receptivity of AN3CA cells to JAR spheroids. Inhibition of endometrial ST6GALNAC1/sTn substantially impaired embryo implantation in vivo. CD44 was identified as a carrier for sTn in the endometrial cells of both species. Siglec-6 and Siglec-G, expressed in the embryonic trophectoderm, were found to promote embryo attachment, which may be achieved through binding with sTn-modified CD44.

Conclusion

ST6GALNAC1-regulated sTn in the endometrium aids in embryo attachment through interaction with trophoblastic Siglecs.

中文翻译：

子宫内膜上皮中 ST6GALNAC1 介导的唾液酸化促进了上皮-胚胎附着

介绍

胚胎植入需要胚胎和接受性子宫内膜之间的协同相互作用。糖蛋白和聚糖结合蛋白参与子宫内膜-胚胎附着。唾液酸酯 Tn （sTn）是一种截短的 O 糖，由 ST6 N-乙酰半乳糖胺 α-2,6-唾液酸转移酶 1 （ST6GALNAC1）催化，可被特异性唾液酸结合免疫球蛋白样凝集素（Siglecs）检测。sTn-Siglecs 轴是否支持胚胎植入仍然未知。

目标

本文旨在研究 ST6GALNAC1/sTn-Siglecs 轴在胚胎植入中的作用。

方法

通过免疫组织化学分析人子宫内膜中的 ST6GALNAC1 和 sTn。进行体外植入模型以评估 ST6GALNAC1/sTn 对人子宫内膜 AN3CA 细胞对 JAR 球体容受性的影响。免疫沉淀结合质谱分析鉴定子宫内膜细胞中 sTn 修饰的关键蛋白。通过已发表的单细胞 RNA 测序（scRNA-seq）数据集分析人类胚胎中的 Siglec-6。采用蛋白质相互作用测定验证 Siglec-6 与 sTn 修饰的 CD44 之间的键合。在植入前阶段将 St6galnac1 siRNAs 和抗 sTn 抗体注射到小鼠的子宫角中，以评估子宫内膜 St6galnac1/sTn 在胚胎植入中的作用。通过免疫荧光染色分析小鼠胚胎中的 Siglec-G。子宫角注射和蛋白质相互作用测定证明了 Siglec-G 的功能。

结果

与非受体阶段相比，人子宫内膜和小鼠子宫内膜在接受期都表现出更高的 ST6GALNAC1 和 sTn 水平。ST6GALNAC1 的过表达显着增强了 AN3CA 细胞对 JAR 球体的容受性。抑制子宫内膜 ST6GALNAC1/sTn 显着损害体内胚胎植入。CD44 被鉴定为两个物种子宫内膜细胞中 sTn 的载体。发现在胚胎滋养外胚层中表达的 Siglec-6 和 Siglec-G 可促进胚胎附着，这可以通过与 sTn 修饰的 CD44 结合来实现。