title: 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.
abstract: 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.
authors.affiliation: Department of Applied Animal Science, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8528, Japan. mashimad@hiroshima-u.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shimada
authors.forename: Masahide
authors.initials: M
authors.lastname: Nishibori
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Junya
authors.initials: J
authors.lastname: Ito
authors.forename: Takahide
authors.initials: T
authors.lastname: Mori
authors.forename: JoAnne S
authors.initials: JS
authors.lastname: Richards
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004151:Dipeptides / Q000494:pharmacology; D019483:Disintegrins / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology*; D008666:Metalloendopeptidases / Q000378:metabolism*; D045726:Metalloproteases / Q000037:antagonists & inhibitors; D015735:Mifepristone / Q000494:pharmacology*; D009865:Oocytes / Q000166:cytology*; D006080:Ovarian Follicle / Q000166:cytology* / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013552:Swine; D013997:Time Factors
chemical_list: D004151:Dipeptides; D019483:Disintegrins; D006727:Hormone Antagonists; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D011480:Protease Inhibitors; D011980:Receptors, Progesterone; D015735:Mifepristone; D045726:Metalloproteases; D008666:Metalloendopeptidases