Biological Functions and Large-Scale Profiling of Protein Glycosylation in Human Semen

Abstract

Glycosylation is one of the most important post-translational modifications of proteins and plays an essential role in spermatogenesis, maturation, extracellular quality control, capacitation, sperm−egg recognition, and final fertilization. Spermatozoa are synthesized in the testes inactively with a thick glycocalyx and passed through the epididymis for further modification by glycosylation, deglycosylation, and integration to reach maturation. Subsequently, sperm capacitation and further fertilization require redistribution of glycoconjugates and dramatic glycocalyx modification of the spermatozoa surface. Furthermore, glycoproteins and glycans in seminal plasma are functional in maintaining spermatozoa structure and stability. Therefore, aberrant glycosylation may cause alteration of semen function and even infertility. Currently, mass spectrometry-based technologies have allowed large-scale profiling of glycans and glycoproteins in human semen. Quantitative analysis of semen glycosylation has also indicated many involved glycoproteome issues in male infertility and the potential biomarkers for diagnosis of male infertility in clinical. This review summarizes the role of glycosylation during spermatozoa development, the large-scale profiling of glycome and glycoproteome in human semen, as well as the association of aberrant glycosylation with infertility.

ZDHHC19 Is Dispensable for Spermatogenesis, but Is Essential for Sperm Functions in Mice

“…Multiple protein post-translational modifications (PTMs) occur in germ cells during spermatogenesis, such as acetylation [2,3], crotonylation [4], glycosylation [5][6][7], phosphorylation [8][9][10], SUMOylation [11], and ubiquitination [12]. Many of these PTMs have been identified to play important roles in sustaining mammalian spermatogenesis and male fertility [13,14].…”

“…Ohno et al investigated the ZDHHCs genes expression patterns in human by RT-PCR, and classified ZDHHC genes into roughly three groups according to their tissue-specific expression patterns: highly ubiquitous, nearly ubiquitous, and tissue-specific [27]. The highly ubiquitous and nearly ubiquitous groups each include most of ZDHHC genes (ZDHHC4, 5,7,8,10,12,13,17,and 22;and ZDHHC1,3,6,9,14,16,18, and 21, respectively), indicating that multiple ZDHHC proteins are co-expressed in the same cell. Interestingly, a small number of ZDHHC genes are tissue-specific, including ZDHHC2, 11, 15, 19, and 20.…”

Seminal Plasma Protein N-Glycan Peaks Are Potential Predictors of Semen Pathology and Sperm Chromatin Maturity in Men

“…N-glycosylation, one of the most prevalent post-translational protein modifications, plays a significant role in interactions between cells and extracellular matrix as well as in protein folding. The glycosylation pattern was shown to be altered in various diseases and conditions, such as male infertility [ 13 ], where the seminal plasma has been extensively explored, as it offers a rich source of N-glyco-biomarkers [ 50 ]. Although seminal plasma surrounds sperm during a short period, protein glycosylation is stable under physiological conditions and can have a significant impact on protein function, as many adhesive properties result from the protein–carbohydrate interactions.…”

“…Although seminal plasma surrounds sperm during a short period, protein glycosylation is stable under physiological conditions and can have a significant impact on protein function, as many adhesive properties result from the protein–carbohydrate interactions. These properties are especially important for proper sperm activation and successful fertilization [ 13 ] since membrane glycoproteins of sperm glycocalyx directly interact with seminal plasma glycoproteins, which affects sperm behavior regarding premature capacitation and immune suppression in the female reproductive tract [ 51 , 52 , 53 ]. Recently, a glycoprotein clusterin (CLU), one of the crucial seminal plasma glycoproteins, has been proposed as a male infertility marker, due to its significant role in sperm capacitation and immune tolerance in the female reproductive tract.…”

“…N-linked protein glycosylation is a process of attachment of sugar moieties to the amide side chain of asparagine residues (in evolutionary conserved sequence asparagine-any amino acid except for proline-serine/threonine) and is one of the most prevalent post-translational protein modifications with a role in mediation interactions between cells and proteins [ 12 ]. Sperm and seminal plasma are rich in glycosylated proteins indispensable for various functions during spermatogenesis, sperm maturation, capacitation and in sperm-egg interaction that finally leads to fertilization [ 13 ]. The contribution of seminal plasma glycoproteins to fertilization is mainly to maintain sperm in a decapacitated state until they reach eggs and to assist sperm during transportation in the female reproductive tract [ 14 ].…”