STUDIES OF MICE LACKING PLASMINOGEN-ACTIVATOR GENE-FUNCTION SUGGEST THAT PLASMIN PRODUCTION PRIOR TO OVULATION EXCEEDS THE AMOUNT NEEDED FOR OPTIMAL OVULATION EFFICIENCY

Many studies suggest that the plasminogen activator (PA) system plays a role in the proteolytic degradation of the follicle wall at the time of ovulation. Consistently, the ovulation efficiency is reduced by 26 % in mice where both physiological PA genes have been inactivated. To reveal the mechanism behind reduced ovulation efficiency in PA-deficie nt mice and its effect on ovarian proteolysis, we have studied the reg ulation of plasmin activity in the ovaries of 25-day-old wild-type mic e and mice with deficient PA gene function during gonadotropin-induced ovulation. In wild type mice the plasmin activity was low in ovarian extracts from mice treated with pregnant mare's serum gonadotropin. Ho wever, this activity was increased between 2-8 h after an ovulatory do se of human choriogonadotropins. In mice lacking either tissue-type PA (tPA) or PA inhibitor type 1 (PAI-1) the plasmin activity levels prio r to ovulation were similar to wild-type mice, while extracts prepared from urokinase-type PA (uPA) deficient mice had 10% or less of the pl asmin activity. This indicates that most of the plasmin activity in th e mice ovary is generated by uPa. In addition, as the ovulation effici ency is impaired in tPA/uPA-deficient mice but appears normal in uPA-d eficient mice, our data indicates that the amount of plasmin generated by PAs prior to ovulation in wild-type mice greatly exceeds the amoun t required for efficient ovulation.