GlycoIP: an integrated platform for simultaneous and site-specific N/O-glycosylation analysis of human semen

Protein glycosylation plays a pivotal role in human semen, influencing various processes, such as spermatogenesis, maturation, sperm motility, capacitation, and fertilization. Despite its importance, the specific details regarding N/O-glycosylation within human semen proteins have largely remained u...

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Main Authors: Gaoshu Yan, Fei Cai, Keliang Wu, Qingyuan Cheng, Yong Zhang, Lin Fan
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Chemistry
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Online Access:https://www.frontiersin.org/articles/10.3389/fchem.2025.1569561/full
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author Gaoshu Yan
Fei Cai
Keliang Wu
Qingyuan Cheng
Yong Zhang
Lin Fan
author_facet Gaoshu Yan
Fei Cai
Keliang Wu
Qingyuan Cheng
Yong Zhang
Lin Fan
author_sort Gaoshu Yan
collection DOAJ
description Protein glycosylation plays a pivotal role in human semen, influencing various processes, such as spermatogenesis, maturation, sperm motility, capacitation, and fertilization. Despite its importance, the specific details regarding N/O-glycosylation within human semen proteins have largely remained unknown. To address this challenge, an integrated glycoproteomic platform (termed GlycoIP) was developed, enabling the simultaneous analysis of both intact N- and O-glycopeptides directly from human semen samples. Characterizing these intact glycopeptides is particularly challenging, yet it provides invaluable insights into the structure and function of both glycans and their attachment sites. In this study, our platform enabled the identification of 1,833 unique N-glycopeptides and 720 unique O-glycopeptides. This approach revealed extensive and precise site-specific N/O-glycosylation data, highlighting 438 potential O-glycosylation sites from 148 distinct O-glycoproteins. Notably, we conducted site-specific N/O-glycosylation profiling on several unique glycoproteins, including sperm equatorial segment protein 1 (SPESP1), which is located on human sperm, and plasma serine protease inhibitor (SERPINA5), which is presented in both sperm and seminal plasma. In summary, this platform provides a promising approach for comprehensive profiling of protein site-specific N/O-glycosylation within a single experiment. This advancement paves the way for further functional studies on glycoproteins and their roles in male infertility, enhancing our understanding of this complex field.
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spelling doaj-art-70e2149da79a465e9cc8806c4c9bcce72025-08-20T03:53:46ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462025-05-011310.3389/fchem.2025.15695611569561GlycoIP: an integrated platform for simultaneous and site-specific N/O-glycosylation analysis of human semenGaoshu Yan0Fei Cai1Keliang Wu2Qingyuan Cheng3Yong Zhang4Lin Fan5Radiation Oncology Key Laboratory of Sichuan Province, Department of Radiology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Nephrology and Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Nephrology and Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Andrology and Sichuan Human Sperm Bank, West China Second University Hospital, Sichuan University, Chengdu, ChinaDepartment of Nephrology and Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaRadiation Oncology Key Laboratory of Sichuan Province, Department of Radiology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, ChinaProtein glycosylation plays a pivotal role in human semen, influencing various processes, such as spermatogenesis, maturation, sperm motility, capacitation, and fertilization. Despite its importance, the specific details regarding N/O-glycosylation within human semen proteins have largely remained unknown. To address this challenge, an integrated glycoproteomic platform (termed GlycoIP) was developed, enabling the simultaneous analysis of both intact N- and O-glycopeptides directly from human semen samples. Characterizing these intact glycopeptides is particularly challenging, yet it provides invaluable insights into the structure and function of both glycans and their attachment sites. In this study, our platform enabled the identification of 1,833 unique N-glycopeptides and 720 unique O-glycopeptides. This approach revealed extensive and precise site-specific N/O-glycosylation data, highlighting 438 potential O-glycosylation sites from 148 distinct O-glycoproteins. Notably, we conducted site-specific N/O-glycosylation profiling on several unique glycoproteins, including sperm equatorial segment protein 1 (SPESP1), which is located on human sperm, and plasma serine protease inhibitor (SERPINA5), which is presented in both sperm and seminal plasma. In summary, this platform provides a promising approach for comprehensive profiling of protein site-specific N/O-glycosylation within a single experiment. This advancement paves the way for further functional studies on glycoproteins and their roles in male infertility, enhancing our understanding of this complex field.https://www.frontiersin.org/articles/10.3389/fchem.2025.1569561/fullspermN-glycosylationO-glycosylationLC-MS/MSglycoproteomics
spellingShingle Gaoshu Yan
Fei Cai
Keliang Wu
Qingyuan Cheng
Yong Zhang
Lin Fan
GlycoIP: an integrated platform for simultaneous and site-specific N/O-glycosylation analysis of human semen
Frontiers in Chemistry
sperm
N-glycosylation
O-glycosylation
LC-MS/MS
glycoproteomics
title GlycoIP: an integrated platform for simultaneous and site-specific N/O-glycosylation analysis of human semen
title_full GlycoIP: an integrated platform for simultaneous and site-specific N/O-glycosylation analysis of human semen
title_fullStr GlycoIP: an integrated platform for simultaneous and site-specific N/O-glycosylation analysis of human semen
title_full_unstemmed GlycoIP: an integrated platform for simultaneous and site-specific N/O-glycosylation analysis of human semen
title_short GlycoIP: an integrated platform for simultaneous and site-specific N/O-glycosylation analysis of human semen
title_sort glycoip an integrated platform for simultaneous and site specific n o glycosylation analysis of human semen
topic sperm
N-glycosylation
O-glycosylation
LC-MS/MS
glycoproteomics
url https://www.frontiersin.org/articles/10.3389/fchem.2025.1569561/full
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