Implantation-associated proteinase in mouse uterine fluid

Proteinase activity was detected in mouse uterine fluid by means of a new casein-substrate assay. The activity was found to be generally low in diestrous and proestrous stages of the estrous cycle and was more variable in proestrous. During pregnancy, activity was very low on day 1 (counting the plug date as day 0). By day 3, proteinase activity (expressed as Pronase equivalents/mg protein of uterine fluid) increased more than 100-fold, and then declined on day 4. Peak activity thus coincides with initiation of embryo implantation, which occurs on day 3 of pregnancy in the strain tested. The results provide direct biochemical support for previous indirect bioassay indications of the presence in uterine fluid of a proteolytic factor of uterine origin. The quantitative changes observed here are also consistent with previous bioassay observations and with the hypothesis that the uterine proteinase may mediate initial attachment of the blastocyst to the uterine wall. These and other data are used to formulate a 2-stage hypothesis of implantation, according to which uterine and trophoblast proteinases act sequentially to cause attachment and invasion, respectively.