MOUSE OOCYTES INHIBIT PLASMINOGEN-ACTIVATOR PRODUCTION BY OVARIAN CUMULUS AND GRANULOSA-CELLS

Following the preovulatory surge of gonadotropins, the compact layer o f cumulus cells in the antral follicle secretes a hyaluronic acid-enri ched extracellular matrix and undergoes a morphological change referre d to as cumulus expansion. It has been previously shown that a soluble factor(s) produced by the oocyte is required, in combination with FSH , to promote this process. Since such matrix is sensitive to proteases we have now studied the effect of the oocyte on another gonadotropin- controlled follicle cell function, i.e., the synthesis of plasminogen activator (PA). Our data indicate that isolated cumulus cells secrete uPA in the medium and that FSH or dbcAMP increases this production. Th e presence of the oocyte or the oocyte-conditioned medium greatly redu ces uPA synthesis induced by FSH and dbcAMP in cumulus cells by modula ting the abundance of its mRNA. The ability of the mouse oocyte to pro duce such a factor(s) is dependent upon its stage of development, with fully grown oocytes but not growing oocytes or two-cell embryos being able to inhibit uPA synthesis. A preliminary characterization of this factor suggests that it is a heat-unstable protein with an apparent m olecular weight above 100 kDa. Thus, the mouse oocytes appear to promo te preovulatory matrix accumulation that occurs just prior ovulation b y modulating the gonadotropin action on both the synthesis and the deg radation of specific matrix component. (C) 1995 Academic Press, Inc.