Human fertilization begins when spermatozoa bind to the extracellular matrix coating of the oocyte, known as the zona pellucida (ZP). One spermatozoan then penetrates this matrix and fuses with the egg cell, generating a zygote. Although carbohydrate sequences on the ZP have been implicated in sperm binding, the nature of the ligand was unknown. Here, ultrasensitive mass spectrometric analyses revealed that the sialyl-Lewis(x) sequence [NeuAcα2-3Galβ1-4(Fucα1-3)GlcNAc], a well-known selectin ligand, is the most abundant terminal sequence on the N- and O-glycans of human ZP. Sperm-ZP binding was largely inhibited by glycoconjugates terminated with sialyl-Lewis(x) sequences or by antibodies directed against this sequence. Thus, the sialyl-Lewis(x) sequence represents the major carbohydrate ligand for human sperm-egg binding.

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Human sperm binding is mediated by the sialyl-Lewis(x) oligosaccharide on the zona pellucida.

Review on t(3;11)(q12;p15) NUP98/LNP1, with data on clinics, and the genes implicated. Clinics and pathology

http://documents.irevues.inist.fr/bitstream/handle/2042/44477/05-2008-t1419q32q13ALLID1335.pdf

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Capacitation is broadly defined as the functional modifications rendering sperm competent to fertilize, encompassing the ability of the sperm to bind the zona pellucida and subsequently undergo the acrosome reaction, hyperactivated motility, and the capacity to fuse with the oocyte. Although discovered in 1951, research over the past 15 years has considerably clarified the mechanisms leading to capacitation. The purpose of this review is to discuss the challenges of studying capacitation and to summarize recent notions regarding its regulation. Of particular interest is an atypical soluble adenylyl cyclase that is stimulated by bicarbonate to activate protein kinase A and drive sperm protein tyrosine phosphorylation. The identities of the phosphorylated sperm-protein substrates and the kinase(s) responsible for their tyrosine phosphorylation have fostered major questions regarding this pathway. Recent investigations, however, have made exciting advances toward resolving these queries. Advanced proteomic approaches have revealed the tyrosine phosphorylated substrates to be implicated in a diverse range of cellular activities. SRC tyrosine kinase is a particularly interesting candidate as the mediator of the protein kinase A-driven sperm protein tyrosine phosphorylation. Future studies are merited to fully characterize additional signaling mediators such as phosphatases and other kinases that may be involved, to elucidate the functional importance of the tyrosine phosphorylation on those particular substrates and to appreciate the differences that may exist among species.

https://www.tandfonline.com/doi/pdf/10.3109/19396368.2010.512377

Factors Regulating Sperm Capacitation

Semenogelin (Sg), the main component of the human semen coagulum, is an important and versatile protein acting on several sperm parameters, both as intact or degraded Sg. Sg originates mostly from seminal vesicle and probably is responsible for sperm immobilization in the seminal coagulum. Purified Sg can be cross-linked by transglutaminase or phosphorylated by kinases, but the actual occurrence of these reactions in reproductive physiology is not clear. Experimental evidence demonstrates that prostate-specific antigen (PSA) rapidly cleaves Sg, an event temporally associated with semen liquefaction and initiation of sperm motility. Sg and its degradation peptides participate in various processes including Zn +2 shuttling, antibacterial activity, hyaluronidase activation, and so on. Sg inhibits sperm motility at the concentration found in the coagulum, but the rapid processing by PSA allows initiation of movement. The mechanism of Sg action and its targets are not known, but improper Sg degradation decreases fertility. Sg and its degradation peptides block sperm capacitation and associated events at concentrations much lower than those of seminal plasma and could play important role in preventing premature capacitation. The effects of Sg are dependent on time and proteolysis due to PSA, and any imbalance may affect sperm physiology and fertility.

Semenogelin, the main protein of the human semen coagulum, regulates sperm function.

Glycodelin is an example of a glycoprotein whose complex-type glycans mediate biological actions in human reproduction and immune reactions. Being attached to an identical protein backbone, glycodelin oligosaccharides vary significantly from one reproductive tissue to another and have an effect on its own secretion and role in cell communication. For instance, uterine glycodelin-A inhibits sperm-oocyte interaction by binding on the sperm head. This is a glycosylation-dependent phenomenon, in which fucosyltransferase-5 plays a key role. Glycodelin-S from seminal plasma binds evenly around the sperm head and maintains an uncapacitated state in the spermatozoa, until the isoform is detached during sperm passage through the cervix. Glycodelin-F from follicular fluid and Fallopian tube binds to the acrosomal region of the sperm head, thereby inhibiting both the sperm-oocyte binding and premature progesterone-induced acrosome reaction. The cumulus cells surrounding the oocyte can capture glycodelin-A and -F from the surrounding environment and convert these isoforms to a cumulus cell isoform, glycodelin-C. It differs by glycosylation from the other isoforms, and it too attaches on the sperm head, with the highest density in the equatorial region. Glycodelin-C is capable of detaching the sperm-bound inhibitory isoforms so that the sperm-oocyte binding is enhanced. Glycodelin-A also has immunosuppressive actions directed to cellular, humoral and innate immunity. Although these actions depend mainly on the protein backbone, glycosylation also plays a part. Glycosylated glycodelin may be involved in the protection of spermatozoa against maternal immune reactions, and glycodelin also has apoptogenic activity. Some glycosylation patterns of glycodelin may mask its apoptogenic domain. This review updates the recent research and clinical associations of glycodelin, highlighting the role of glycosylation.

Heng-Yan Tsang

Papers

Glycodelin-S in Human Seminal Plasma Reduces Cholesterol Efflux and Inhibits Capacitation of Spermatozoa