Seminal clotting and fibrinolytic balance: a possible physiological role in the male reproductive system
Bashir A. Lwaleed1, Robert Greenfield2, Alistair Stewart1, Brian Birch1,Alan J. Cooper1
1Department of Urology, Southampton University Hospitals,Tremona Road, Southampton, UK 2American Diagnostic Inc, Stamford, Connecticut, USA
Summary
Semen contains enzymes and inhibitors of the haemostaticsystem as well as the high molecular weight seminal vesicle(HMW-SV) proteins. The former may have roles in seminalclotting and in liquefaction through “fibrinolytic” activity, whichmay ultimately affect fertility. Although a limited number ofstudies have addressed the subject, the role of clotting andfibrinolytic factors in semen remains poorly understood. Theliquefaction time and the distribution of components varyacross split ejaculates. This may have an important bearing onthe way clotting/fibrinolytic factors in semen are assessed.Semen contains tissue factor (TF, Thromboplastin, CD142),which originates from the prostate and is associated with prostasomes.The function of TF (and prostasomes) in semen is stilla matter for speculation. Recently the presence of minuteamounts of factor VII in semen has been demonstrated but itsimportance is uncertain. Semen also contains a thrombin-likeenzyme, prothrombin fragments 1 and 2 (F1+2), D-dimer (DD)and thrombin-antithrombin (TAT) complexes. The presence ofseveral fibrinolytic factors has been demonstrated in semen butfew questions about their potential impact on semen qualityhave been raised. Factors found include tissue plasminogen activator (t-PA), urinary plasminogen activator (u-PA) andplasmin.There are also traces of fibrinogen, plasminogen, plasminogenactivator inhibitor-1 (PAI-1), factor VIII coagulant activity(VIII:c) and fibrin monomers.The co-ordinate expression ofboth TF and PAI-1 by decidual cells of the endometrium isbelieved to be important in maintaining haemostasis duringendovascular trophoblast invasion. Kallikrein-like serine proteaseinhibitors including prostate specific antigen (PSA) areknown to be present in semen at high concentrations. In semenPSA is also found in a complex form with protein C inhibitor(PCI) with mutually inhibitory consequences. A better understandingof the spectrum of coagulating and liquefaction agentsin semen to include classical haemostatic processes and thepathogenesis resulting from any imbalances between or withineither system may provide the basis for the development ofmore selective and efficient agents affecting global fertility. Herewe review aspects of male reproductive physiology in the lightof recent findings concerning conventional clotting/fibrinolyticsystems in human semen with a view to stimulating furtherresearch. DOI
http://dx.doi.org/10.1160/TH04-03-0142