BACKGROUND The establishment of maternal-fetal crosstalk is vital to a successful pregnancy. Glycosylation is a post-translational modification in which glycans (monosaccharide chains) are attached to an organic molecule. Glycans are involved in many physiological and pathological processes. Human endometrial epithelium, endometrial gland secretions, decidual immune cells, and trophoblasts are highly enriched with glycoconjugates and glycan-binding molecules important for a healthy pregnancy. Aberrant glycosylation in the placenta and uterus has been linked to repeated implantation failure and various pregnancy complications, but there is no recent review summarizing the functional roles of glycosylation at the maternal-fetal interface and their associations with pathological processes. OBJECTIVE AND RATIONALE This review aims to summarize recent findings on glycosylation, glycosyltransferases, and glycan-binding receptors at the maternal-fetal interface, and their involvement in regulating the biology and pathological conditions associated with endometrial receptivity, placentation and maternal-fetal immunotolerance. Current knowledge limitations and future insights into the study of glycobiology in reproduction are discussed. SEARCH METHODS A comprehensive PubMed search was conducted using the following keywords: glycosylation, glycosyltransferases, glycan-binding proteins, endometrium, trophoblasts, maternal-fetal immunotolerance, siglec, selectin, galectin, repeated implantation failure, early pregnancy loss, recurrent pregnancy loss, preeclampsia, and fetal growth restriction. Relevant reports published between 1980 and 2023 and studies related to these reports were retrieved and reviewed. Only publications written in English were included. OUTCOMES The application of ultrasensitive mass spectrometry tools and lectin-based glycan profiling has enabled characterization of glycans present at the maternal-fetal interface and in maternal serum. The endometrial luminal epithelium is covered with highly glycosylated mucin that regulates blastocyst adhesion during implantation. In the placenta, fucose and sialic acid residues are abundantly presented on the villous membrane and are essential for proper placentation and establishment of maternal-fetal immunotolerance. Glycan-binding receptors, including selectins, sialic-acid-binding immunoglobulin-like lectins (siglecs) and galectins, also modulate implantation, trophoblast functions and maternal-fetal immunotolerance. Aberrant glycosylation is associated with repeated implantation failure, early pregnancy loss and various pregnancy complications. The current limitation in the field is that most glycobiological research relies on association studies, with few studies revealing the specific functions of glycans. Technological advancements in analytic, synthetic and functional glycobiology have laid the groundwork for further exploration of glycans in reproductive biology under both physiological and pathological conditions. WIDER IMPLICATIONS A deep understanding of the functions of glycan structures would provide insights into the molecular mechanisms underlying their involvement in the physiological and pathological regulation of early pregnancy. Glycans may also potentially serve as novel early predictive markers and therapeutic targets for repeated implantation failure, pregnancy loss, and other pregnancy complications.

中文翻译：

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蛋白质糖基化在人类母胎串扰中的功能作用。


背景技术母婴串扰的建立对于成功妊娠至关重要。糖基化是一种翻译后修饰，其中聚糖（单糖链）连接到有机分子上。聚糖参与许多生理和病理过程。人类子宫内膜上皮、子宫内膜腺分泌物、蜕膜免疫细胞和滋养层富含糖复合物和聚糖结合分子，这对健康妊娠至关重要。胎盘和子宫中的异常糖基化与反复着床失败和各种妊娠并发症有关，但最近没有综述总结糖基化在母胎界面的功能作用及其与病理过程的关系。目的和基本原理本综述旨在总结母胎界面糖基化、糖基转移酶和聚糖结合受体的最新发现，以及它们在调节与子宫内膜容受性、胎盘和母胎免疫耐受相关的生物学和病理条件中的作用。讨论了生殖糖生物学研究的当前知识局限性和未来见解。检索方法 使用以下关键词进行全面的 PubMed 检索：糖基化、糖基转移酶、聚糖结合蛋白、子宫内膜、滋养细胞、母胎免疫耐受、siglec、选择素、半乳糖凝集素、反复着床失败、早期妊娠丢失、复发性妊娠丢失、先兆子痫和胎儿生长受限。检索并审查了1980年至2023年间发表的相关报告以及与这些报告相关的研究。仅包括用英文撰写的出版物。 结果超灵敏质谱工具和基于凝集素的聚糖分析的应用使得能够对母胎界面和母体血清中存在的聚糖进行表征。子宫内膜腔上皮覆盖有高度糖基化的粘蛋白，可在植入过程中调节囊胚的粘附。在胎盘中，岩藻糖和唾液酸残基大量存在于绒毛膜上，对于胎盘的正常形成和母胎免疫耐受的建立至关重要。聚糖结合受体，包括选择素、唾液酸结合免疫球蛋白样凝集素 (siglecs) 和半乳糖凝集素，也调节着床、滋养层功能和母胎免疫耐受。异常糖基化与反复着床失败、早期妊娠流产和各种妊娠并发症有关。目前该领域的局限性在于，大多数糖生物学研究依赖于关联研究，很少有研究揭示聚糖的具体功能。分析、合成和功能糖生物学的技术进步为进一步探索生理和病理条件下生殖生物学中的聚糖奠定了基础。更广泛的意义 对聚糖结构功能的深入了解将有助于深入了解其参与早期妊娠生理和病理调节的分子机制。聚糖还可能作为反复着床失败、妊娠流产和其他妊娠并发症的新型早期预测标记物和治疗靶点。