title: Altered expression of Fas/Fas ligand/caspase 8 and membrane type 1-matrix metalloproteinase in atretic follicles within dehydroepiandrosterone-induced polycystic ovaries in rats.
abstract: One of the characteristics of polycystic ovary syndrome (PCOS) is the presence of cystic follicles in various stages of growth and atresia, the latter of which is known to be the result of apoptosis and tissue remodeling. To further investigate the process of follicular atresia, we compared ovarian expression and localization of Fas, Fas ligand (FasL), casapse-8 and membrane-type1 matrix metalloproteinase (MT1-MMP) in rats treated with dehydroepiandrosterone (DHEA) as a model of PCOS, and in control rats. We found that the numbers of TdT-mediated dUTP-biotin nick end-labeling (TUNEL)-positive follicles were significantly higher in ovaries from PCOS rats than in those from control rats (P < 0.05), as were ovarian levels of FasL mRNA and protein, processed caspase-8 protein and MT1-MMP mRNA. Correspondingly, we also observed an increase in the level of MTI-MMP catalytic activity and a decrease in the level of pro-caspase-8 protein. In addition, immunohistochemical analyses showed that MT1-MMP and FasL co-localize with TUNEL-positive apoptotic granulosa cells within atretic follicles of PCOS ovaries. Our results suggest that under the PCOS-like conditions induced by DHEA, the Fas/FasL/Caspase-8 (death receptor dependent) pathway is pivotal for follicular atresia, and that increased levels of MT1-MMP likely play an important role in tissue remodeling during structural luteolysis.
authors.affiliation: Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, South 1 West 16, Sapporo, 060-8543, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Honnma
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Endo
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Henmi
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Nagasawa
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Baba
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Kitajima
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Hayashi
authors.forename: Kengo
authors.initials: K
authors.lastname: Manase
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053181:Caspase 8 / Q000378:metabolism*; D003687:Dehydroepiandrosterone; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000378:metabolism*; D005260:Female; D053504:Matrix Metalloproteinases, Membrane-Associated / Q000378:metabolism*; D006080:Ovarian Follicle / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D053222:Fas Ligand Protein; D012333:RNA, Messenger; D019014:fas Receptor; D003687:Dehydroepiandrosterone; C505528:Casp8 protein, rat; D053181:Caspase 8; D053504:Matrix Metalloproteinases, Membrane-Associated