Semenogelin, the Main Protein of the Human Semen Coagulum, Regulates Sperm Function

ABSTRACT

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.

KEYWORDS

Semenogelin - prostate specific antigen - sperm motility - sperm capacitation - semen coagulum

REFERENCES

• 1 Robert M, Gagnon C. Semenogelin I: a coagulum forming, multifunctional seminal vesicle protein.  Cell Mol Life Sci. 1999;  55 944-960
• 2 Lundwall A, Bjartell A, Olsson A, Malm J. Semenogelin I and II, the predominant human seminal plasma proteins, are also expressed in non-genital tissues.  Mol Hum Reprod. 2002;  8 805-810
• 3 Lwaleed B A, Greenfield R, Stewart A, Birch B, Cooper A J. Seminal clotting and fibrinolytic balance; a possible physiological role in the male reproductive system.  Thromb Haemost. 2004;  92 752-766
• 4 Lilja H, Abrahamsson P A, Lundall A. Semenogelin, the predominant protein in human semen. Primary structure and identification of closely related proteins in the male accessory sex glands and on the spermatozoa.  J Biol Chem. 1989;  264 1894-1900
• 5 Lilja H. Cell biology of semenogelin.  Andrologia. 1990;  22 132-141
• 6 Lilja H, Lundwall A. Molecular cloning of epididymal and seminal vesiclar transcripts encoding a semenogelin-related protein.  Proc Natl Acad Sci USA. 1992;  89 4559-4563
• 7 Aumuller G, Seitz J, Lilja H, Abrahamsson P A, von der Kammer H, Scheit K H. Species and organ specificity of secretory proteins derived from human prostate and seminal vesicles.  Prostate. 1990;  17 31-40
• 8 de Lamirande E, Yoshida K, Yoshiike M, Iwamoto T, Gagnon C. Semenogelin, the main protein of semen coagulum, inhibits human sperm capacitation by interfering with the superoxide anion generated during this process.  J Androl. 2001;  22 672-679
• 9 Robert M, Gibbs B F, Jacobson E, Gagnon C. Characterization of prostate-specific antigen proteolytic activity on its major physiological substrate, the sperm motility inhibitor precursor/semenogelin I.  Biochemistry. 1997;  36 3811-3819
• 10 Balk S P, Ko Y-J, Bubley G J. Biology of prostate-specific antigen.  J Clin Oncol. 2003;  21 383-391
• 11 Jonsson M, Linse S, Frohm B, Lundwall A, Malm J. Semenogelins I and II blind zinc and regulate the activity of prostate-specific antigen.  Biochem J. 2005;  387 447-453
• 12 de Lamirande E, Belles-Isles M, Gagnon C. Characteristics of a seminal plasma inhibitor of sperm motility. Hormone action and testicular function.  Ann NY Acad Sci. 1984;  438 125-131
• 13 Iwamoto T, Gagnon C. A human seminal plasma protein blocks the motility of human spermatozoa.  J Urol. 1988;  140 1045-1048
• 14 Iwamoto T, Gagnon C. Purification and characterization of a sperm motility inhibitor in human seminal plasma.  J Androl. 1988;  9 377-383
• 15 Deperthes D, Frenette G, Brillard-Bourdet M, Bourgeois L, Gauthier F, Tremblay R R. Potential involvement of kallikrein hK2 in the hydrolysis of the human seminal vesivle proteins after ejaculation.  J Androl. 1996;  17 659-665
• 16 Robert M, Gagnon C. Sperm motility inhibitor from human seminal plasma: presence of a precursor molecule in seminal vesicle fluid and its molecular processing after ejaculation.  Int J Androl. 1994;  17 232-240
• 17 Brillard-Bourdet M, Réhault S, Juliano L, Ferrer M, Moreau T, Gauthier F. Amidolytic activity of prostatic acid phosphatase on human semenogelins and semenogelin-derived synthetic substrates.  Eur J Biochem. 2002;  269 390-395
• 18 Robert M, Gagnon C. Sperm motility inhibitor from human seminal plasma: association with semen coagulum.  Hum Reprod. 1995;  10 2192-2197
• 19 Robert M, Gagnon C. Purification and characterization of the active precursor of a human sperm motility inhibitor secreted by the seminal vesicles: identity with semenogelin.  Biol Reprod. 1996;  55 813-821
• 20 Williams-Ashman H G. Transglutaminases and the clotting of mammalian seminal fluids.  Mol Cell Biochem. 1984;  58 51-61
• 21 Peter A, Lilja H, Lundwall A, Malm J. Semenogelin I and semenogelin II, the major gel-forming proteins in human semen, are substrates for transglutaminase.  Eur J Biochem. 1998;  252 216-221
• 22 Ek P, Malm J, Lilja H, Carlsson L, Ronquist G. Exogenous protein kinases A and C, but not endogenous prostasome-associated protein kinase, phosphorylate semenogelins I and II from human semen.  J Androl. 2002;  23 806-814
• 23 Bjartell A, Malm J, Gunnarsson N, Lundwell A, Lilja H. Distribution and tissue expression of semenogelin I and II in man as demonstrated by in situ hybridization and immunochemistry.  J Androl. 1996;  17 17-26
• 24 Oshio S, Kaneko S, Iisuka R, Mohri H. Sialic acid in purified human sperm.  Arch Androl. 1987;  18 225-230
• 25 Zalensky A O, Yau P, Brenerman J W, Bradbury E M. The abundant 19-kilodalton protein associated with human sperm nuclei that is related to seminal plasma alpha-inhibin.  Mol Reprod Dev. 1993;  36 164-173
• 26 Kjellberg S, Bjorndahl L, Kvist U. Sperm chromatin stability and zinc binding properties in semen from men in barren unions.  Int J Androl. 1992;  15 103-113
• 27 Mandal A, Bhattacharyya A K. Sperm hyaluronidase activation by purified predominant and major basic human seminal coagulum proteins.  Hum Reprod. 1995;  10 1745-1750
• 28 Bourgeon F, Evrard B, Brillard-Bourdet M, Colleu D, Jégou B, Pineau C. Involvement of semenogelin-derived peptides in the antibacterial activity of human seminal plasma.  Biol Reprod. 2004;  70 768-774
• 29 Wang Z, Widgren E E, Sivashanmugam P, O'Rand M G, Richardson R T. Association of eppin with semenogelin on human spermatozoa.  Biol Reprod. 2005;  72 1064-1070
• 30 de Lamirande E, Bardin W C, Gagnon C. Aprotinin and a seminal plasma factor inhibit the motility of demembranated reactivated rabbit spermatozoa.  Biol Reprod. 1983;  28 788-796
• 31 de Lamirande E, Gagnon C. Aprotinin and a seminal plasma factor provide two new tools to study the regulation of sperm motility.  J Submicrosc Cytol. 1983;  15 83-87
• 32 Gagnon C, de Lamirande E. Controls of sperm motility. In: De Jonge C, Barratt C The Sperm Cell: Production, Maturation, Fertilization, Regeneration. Cambridge; Cambridge University Press 2006: 108-133
• 33 de Lamirande E, Sherins J R, Gagnon C. The presence of a motility inhibitor within spermatozoa may explain the poor sperm motility of some infertile men.  J Androl. 1986;  7 215-219
• 34 Luterman M, Iwamoto T, Gagnon C. Origin of the human seminal plasma motility inhibitor within the reproductive tract.  Int J Androl. 1991;  14 91-98
• 35 Yanagimachi R. Mammalian fertilization. In: Knobil E, Neill JD The Physiology of Reproduction. New York; Raven Press 1994: 189-317
• 36 de Lamirande E, Leclerc P, Gagnon C. Capacitation as a regulatory event that primes spermatozoa for the acrosome reaction and fertilization.  Mol Hum Reprod. 1997;  3 175-194
• 37 De Jonge C. Biological basis for human capacitation.  Hum Reprod. Update 2005;  11 205-214
• 38 Olds-Clarke P. Unresolved issues in mammalian fertilization.  Int Rev Cytol. 2003;  232 129-184
• 39 O'Flaherty C, de Lamirande E, Gagnon C. Positive role of reactive oxygen species in mammalian sperm capacitation: triggering and modulation of phosphorylation events.  Free Radic Biol Med. 2006;  41 528-540
• 40 Cormier N, Sirard M-A, Bailey J L. Premature capacitation of bovine spermatozoa is initiated by cryopreservation.  J Androl. 1997;  18 461-468
• 41 Chiu P CN, Chung M-K, Tsang H-Y et al.. Glycodelin-S in human seminal plasma reduces cholesterol efflux and inhibits capacitation of spermatozoa.  J Biol Chem. 2005;  280 25580-25589
• 42 de Lamirande E, Gagnon C. Human sperm hyperactivation and capacitation as parts of an oxidative process.  Free Radic Biol Med. 1993;  14 157-166
• 43 de Lamirande E, Gagnon C. Capacitation-associated production of superoxide anion by human spermatozoa.  Free Radic Biol Med. 1995;  18 487-496
• 44 Zhang H, Zheng R. Promotion of human sperm capacitation by superoxide anion.  Free Radic Res. 1996;  24 261-268
• 45 Aitken R J, Harkiss D, Knox W, Paterson M, Irvine D S. A novel signal transduction cascade in capacitating human spermatozoa characterized by a redox-regulated cAMP-mediated induction of tyrosine phosphorylation.  J Cell Sci. 1998;  111 645-656
• 46 Herrero M B, Chatterjee S, Lefievre L, de Lamirande E, Gagnon C. Nitric oxide interacts with the cAMP pathway to modulate capacitation of human spermatozoa.  Free Radic Biol Med. 2000;  29 522-536
• 47 Andrews J C, Noland J P, Hammerstedt R H, Bavister B D. Role of zinc in hamster sperm capacitation.  Biol Reprod. 1994;  51 1238-1247