Studies on the relationship between urokinase plasminogen activator (uPA) and human sperm motility

Abstract

To clarify the role of urokinase plasminogen activator (uPA) in the mechanisms of regulating sperm motility and the ability of fertilizing, we investigated the quantities and activities of uPA in human seminal plasma and on the membrane of spermatozoa. Semens were harvested from 22 infertile patients with asthenospermia and 20 healthy fertile men according to WHO standards. To quantify the membrane-bound uPA in the samples, polyclonal antibodies against human urokinase were employed by means of a sandwich ELISA. The uPA activities in seminal plasma and on the surface of spermatozoa were determined using A-garose-Fibrine-Plate method and the experiment of immunological identification with polyclonal antibodies against urokinase. In lysates of spermatozoa, significantly lower levels of uPA (23. 1±7. 35 mu/10⁶ cells) and uPA activity (5. 13±3. 85 mu/10⁶ cells) were found in patient group as compared to healthy fertile men exhibiting normospermia (29. 89±9. 40 mu/10⁶ cells and 10. 17±6. 18 mu/10⁶ cells). In seminal plasma, uPA activity in patient group (2134 ± 1581. 3 IU/L) was also found significantly lower than that of normal group (3365 ± 1859. 5 IU/ L). Positive correlations were observed between sperm motility and uPA quantities (r=0, 48,P<0. 005), as well as with uPA activities (r = 0. 45,P<0. 005). Thus, it is inferred that membrane associated uPA on human spermatozoa may be related directly to sperm motility and fertility.

Keywords

urokinase plasminogen activator / sperm motility / asthenospermia

References

[1] ZaneveldL J D, PolakoskiK L, SchumacherG F B. ReichE, RifkinD, ShawE. The proteolytic enzyme system of mammalian genital tract secretions and spermatozoa. Protease and Biological Control, 1975, New York, Cold Spring Harbour: 683-706

[2] MacGregor I R, HargreaveT B, EltonR A. Seminal plasma plasminogen activator and fertility. Andrologia, 1987, 19: 452-452

[3] ReichE. BerlinR D, HermannH, LeprowI M, TanzenJ H. Activation of plasminogen: a general mechanism for producing localized extracellular proteolysis. Molecular Basis of Biological Degradative Processes, 1978, New York, Academic Press: 155-169

[4] SmokovitisA, KokolisN, AlexopoulosC, et al. . Plasminogen activator activity, plasminogen activator inhibition and plasmin inhibition in spermatozoa and seminal plasma of man and various animal species. Effect of plasmin on sperm motility. Fibrinolysis, 1987, 1: 253-253

[5] HongC Y, ChiangB N, HuangJ J, et al. . Two plasminogen activators, streptokinase and urokinase stimulate human sperm motility. Andrologia, 1985, 17: 317-317

[6] HuarteJ, BerlinD, BoscoD, et al. . Plasminogen activator and mouse spermatozoa: urokinase synthesis in the male genital tract and binding of the enzyme to the sperm cell surface. J Cell Biol, 1987, 104: 1281-1281

[7] MaierU, KirchheimerJ C, HienertG, et al. . Fibrinolytic parameters in spermatozoa and seminal plasma. J Urol, 1991, 146: 906-906

[8] Gronelli-PiperoA Reich. A study of proteases and protease-inhibitor complexes in biological fluids. J Exp Med, 1978, 148: 223-223

[9] 1321 1990,4:92

[10] RekkasC, BelibasakiS, TaitzoglouI, et al. . Increased plasminogen activator activity and plasminogen activator inhibition in spermatozoa and seminal plasma of the ram after serum gonadotrophine (PMSG) adminstration. Correlation with the increased level of testosterone in the blood. Andrologia, 1991, 23: 273-273

[11] VassalliJ D, BaccinoD, BelinD. A cellular binding site for the Mr 55 000 form of the human plasminogen activator urokinase. J Cell Biol, 1985, 100: 86-86

[12] BlasF. Surface receptors for urokinase plasminogen, activator. Fibrinolysis, 1988, 2: 73-73

[13] 1995, 4(3):164

[14] AustinC R, BishopM W H. Fertilization in mammals. Biol Rev Camb Philos. Soc, 1957, 32: 296-296

[15] Xiong C L, Huang X B, Xia W Jet al. The immunohistochemical localization of urokinasetype plasminogen activator (uPA) and urokinase-type activator receptor (uPAR) in human spermatozoa. J Androtogy, 1996,Suppl:58