P-077 The role of glycosylation in the male reproduction revealed by omics technologies
Authors: Cheng Q , Luo M , Xu Z , Li F , Zhang Y 
Published: July 2024

Abstract

Study question
What is the current status of art and future perspective of glycosylation in the male reproduction using omics-based technology?

Summary answer
The precise site-specific glycoproteome of fertile human semen was generally established while the alteration in the pathogenic processes needed to be further investigated.

What is known already
The entire lifespan of human sperm concomitant with the glycosylation, which have been considered to be profoundly implicated in the male reproduction. In the past, only a few glycan patterns or glycoproteins in the male reproductive system were characterized due to technical limitations. Traditional strategies based on either glycomics or deglycosylated proteomics also are far from sufficient for fully understanding glycosylation in male reproduction. The development of the precise site-specific glycosylation of human semen was profiled, which laid a foundation on subsequently unveiling its role, while many challenging questions remain and require the assistance of advanced glycoproteomics.

Study design, size, duration
The original research and reviews in the PubMed and Web of Science databases were searched using terms regarding glycoproteome and male reproduction until September 2023.

Participants/materials, setting, methods
PubMed and Web of Science were used to search articles and reviews with the following main keywords pertaining to the glycoproteomics: “glycosylation”, “glycan”, “glycoprotein”, “glycome”, “glycoproteome”, “glycomics” and “glycoproteomics”, combined with “semen”, “spermatozoa”, “seminal plasma”, “epididymis”, “fertilization” and other key terms related to male reproduction. The search period included all publications until now (September 2023). The language was limited to English, and the species in most studies was limited to humans.

Main results and the role of chance
The precise site-specific glycoproteome of fertile human ejaculate spermatozoa and seminal plasma was generally established. Both are highly abundant in glycans and glycoproteins and share heavy fucosylation as the most significant feature. Their functions are mainly involved in immunomodulation, capacitation, and sperm-oocyte binding. Spatiotemporal regulation was found in glycosylation during male reproduction. Intracellular glycan synthesis occurs in testicular sperm, and a variety of glycan-modifying enzymes and extracellular vesicles are responsible for sperm maturation. Alterations in the semen glycoproteome were observed in male reproduction disorders and are associated with oligoasthenozoospermia, decreased sperm function, male accessory gland disease and immune dysregulation. Impaired glycosylation may be the result of genetic, endocrine, and oxidative stress and infection. Some idiopathic male infertility may be attributed to glycosylation abnormalities. Hence, glycoproteins have the potential to be biomarkers in male reproductive diseases and assisted reproductive technology. We point out that the mapping of the normal semen N-glycoproteome was the first step and there are many challenges such as the identification of the O-linked glycoproteome. Advanced glycoproteomic techniques developed recently have the potential to address them and promote the glycoproteome research in male reproduction.

Limitations, reasons for caution
There are no more than 20 articles regarding the glycomics or glycoproteomics of the semen and the samples processing is not ideal.

Wider implications of the findings
Our work hope to enlighten the biologists to depict the overall landscape of the male reproductive glycoproteome including spermatogenesis and maturation. Moreover, we provide adequate information for reproductive clinicians and technicians for the clinical translation of glyco-related biomarkers and therapeutic targets.

Trial registration number
not applicable