Chemoselective lab eling-base d spermatozoa glycan imaging reveals abnormal glycosylation in oligoasthenotspermia

Chemoselective lab eling-base d spermatozoa glycan imaging reveals abnormal glycosylation in oligoasthenotspermia
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DOI:
10.1016/j.cclet.2023.108760
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发表时间:
2024-02-02
影响因子:
9.1
通讯作者:
Ju,Huangxian
Ju,Huangxian
中科院分区:
化学1区
文献类型:
--
作者:
Xu,Lijia;Zhong,Tong;Ju,Huangxian

文献摘要

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精子发生、成熟、获能和受精都受糖基化的精确调控。然而,糖基化模式改变与生殖疾病的发生和发展之间的关系尚不清楚,主要是由于缺乏对精子糖基化的现场成像技术。基于唾液酸(Sia)和N-乙酰-D-氨基半乳糖(Gal/GalNAc)的化学选择性标记,我们开发了一种高效、高特异性的精子多糖成像技术。我们进一步提出了一种“串联多聚糖化学选择性标记”策略,以实现两种类型的多聚糖在精子上的同时成像。我们将开发的方法应用于少精子症患者和糖尿病小鼠的精子,发现这些精子显示出比正常组更高水平的Sia和Gal/GalNAc表达。此外,糖尿病小鼠的精子数量、存活率和前向活动率严重下降,提示活糖代谢紊乱可能导致精子糖基化水平升高,并与少弱精子症的发生有关。我们的工作为揭示糖基化修饰与精子质量之间的关系提供了一个研究工具,也为基于糖链的生殖标记的开发提供了一条有希望的线索。
Spermatogenesis, maturation, capacitation and fertilization are precisely regulated by glycosylation. However, the relationship between altered glycosylation patterns and the onset and development of reproductive disorders is unclear, mainly limited by the lack ofin situimaging techniques for spermatozoa glycosylation. We developed an efficient and highly specific spermatozoa glycan imaging technique based on the robust chemoselective labeling of sialic acid (Sia) andN-acetyl-d-galactosamine (Gal/GalNAc). We further proposed a “tandem glycan chemoselective labeling” strategy to achieve simultaneous imaging of two types of glycans on spermatozoa. We applied the developed method to the spermatozoa from oligozoospermic patients and diabetic mice and found that these spermatozoa showed higher levels of Sia and Gal/GalNAc expression than the normal groups. Moreover, spermatozoa from diabetic mice showed a severe decrease in number, viability, and forward motility, suggesting thatin vivoglucose metabolism disorders may lead to an elevated level of spermatozoa glycosylation and have a correlation with the development of oligoasthenotspermia. Our work provides a research tool to reveal the relationship between glycosylation modification and spermatozoa quality, and a promising clue for the development of glycan-based reproductive markers.