Down-regulated expression of A disintegrin and metalloproteinase with thrombospondin-like repeats-1 by progesterone receptor antagonist is associated with impaired expansion of porcine cumulus-oocyte complexes

ADAMTS-1, a member of the A disintegrin and metalloproteinase family of proteases, is expressed in rodent follicles via progesterone receptor (PR)-dependent pathways. However, the functional relationship between ADAMTS-1 expression and PR has not been studied extensively in other species. In the present study, we investigated the time-dependent changes in ADAMTS-1 expression in cumulus cells of porcine cumulus-oocyte complexes (COCs), and the roles of ADAMTS-1 in cumulus expansion during in vitro maturation of oocytes. ADAMTS-1 message was not detected in cumulus cells at the time of collection from the follicles. In response to gonadotropins, ADAMTS-1 mRNA was dramatically up-regulated and reached a maximum at 20 h. The level of mature ADAMTS-1 protein increased in a time-dependent manner with a maximum level at 40 h. The induction of ADAMTS-1 mRNA and protein was significantly decreased by the addition of PR antagonist RU486 to the cultures. However, RU486 did not affect the expression of ADAMTS-4 or factors that had been reported to be required for COC expansion (TSG-6, versican, HA synthase-2). COCs cultured with FSH and LH for 40 h exhibited prominent cumulus expansion. The expansion was reduced significantly by the addition of either RU486 or Galardin, a broad-spectrum matrix metalloproteinase inhibitor. These results suggest that the expression and induction of ADAMTS-1 through receptor-mediated action of progesterone in cumulus cells is one of the essential requirements for gonadotropin-regulated cumulus expansion of porcine COCs.