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Submitted on April 27, 2004
Accepted on June 25, 2004
Department of Applied Animal Science, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima, Hiroshima, 739-8528, Japan, Infertility Center, Daigo-Watanabe Clinic, Kyoto, 601-1375, Japan, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, 77030
* To whom correspondence should be addressed. E-mail: mashimad{at}hiroshima-u.ac.jp.
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 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 progesterone receptor 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, HAS-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.
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