OVULATION EFFICIENCY IS REDUCED IN MICE THAT LACK PLASMINOGEN-ACTIVATOR GENE-FUNCTION - FUNCTIONAL REDUNDANCY AMONG PHYSIOLOGICAL PLASMINOGEN ACTIVATORS

Several lines of indirect evidence suggest that plasminogen activation plays a crucial role in degradation of the follicular wall during ovu lation. However, single-deficient mice lacking tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), or PA in hibitor type 1 (PAI-1) gene function were recently found to have norma l reproduction, although mice with a combined deficiency of tPA and uP A were significantly less fertile. To investigate whether the reduced fertility of mice lacking PA gene function is due to a reduced ovulati on mechanism, we have determined the ovulation efficiency in 25-day-ol d mice during gonadotropin-induced ovulation. Our results reveal that ovulation efficiency is normal in mice with a single deficiency of tPA or uPA but reduced by 26% in mice lacking both physiological PAs. Thi s result suggests that plasminogen activation plays a role in ovulator y response, although neither tPA nor uPA individually or in combinatio n is obligatory for ovulation. The loss of an individual PA seems to b e Functionally complemented by the remaining PA but this compensation does not appear to involve any compensatory up-regulation. Our data im ply that a functionally redundant mechanism for plasmin formation oper ates during gonadotropin-induced ovulation and that PAs together with other proteases generate the proteolytic activity required for follicu lar wall degradation.