Involvement of plasminogen activator and plasminogen activator inhibitor type 1 in spermatogenesis, sperm...

Increasing evidence suggests that local fibrinolysis generated by plasminogen activator (PA) and modulated by plasminogen activator inhibitor type 1 (PAI-1) is essential for mammalian spermatogenesis, sperm capacitation, and fertilization. Tissue-type PA (t-PA), urokinase-type PA (u-PA), and PAI-1 have been reported in the testes of various animals. Sertoli cells within the seminiferous epithelium are believed to play a central role in the control and maintenance of spermatogenesis by producing regulatory factors, including PA/PAI-1. Fertilization is a unique and exquisitely choreographed cellular interaction between male and female gametes, in which some basic biochemical mechanisms remain unresolved. A key issue is the molecular basis of sperm-egg recognition, binding, and penetration. Sperm capacitation and the acrosomal reaction appear to rely on local fibrinolysis generated by the PA/PAI-1 system. Ejaculated spermatozoa from various species carry u-PA activity. The u-PA receptor (uPAR) and the inhibitor PAI-1 have also been reported to bind on the sperm membrane surface. Thus, it is possible that uPAR and PAI-1 function in a counterbalanced and coordinated way on the surface of spermatozoa to regulate the u-PA binding capacity. This review summarizes evidence for the involvement of PA/PAI-1 system in spermatogenesis, sperm capacitation, and fertilization.