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Expression of Urokinase-Type Plasminogen Activator and Its Receptor during Ovarian Follicular Development¹

Reproductive Biology Unit, Departments of Obstetrics and Gynecology and Physiology (M.L, E.G.K., J.A.C., B.K.T.) and Department of Anatomy and Neurobiology (J.N.F.), University of Ottawa and the Ottawa Civic Hospital Loeb Research Institute (M.L., E.G.K., B.K.T.), Ottawa, Ontario, Canada KIY 4E9; and Departments of Medicine and Physiology (R.X., S.A.R.), McGill University, Montreal, Quebec, Canada and Centre for Food and Animal Research and Agriculture and Agri-food Canada (J.A.C.), Ontario, Canada KIA 0C6

Address all correspondence and requests for reprints to: Dr. Benjamin K. Tsang, Reproductive Biology Unit, Department of Obstetrics and Gynaecology, Ottawa Civic Hospital, 1053 Carling Avenue, Ottawa, Ontario, Canada, K1Y 4E9.

Although tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) are believed to be involved in the biochemical cascade leading to extracellular matrix degradation during ovulation, the presence and possible role of urokinase-type PA (uPA) and its receptor (uPAR) in follicular wall remodeling during follicular development are poorly understood. In the current studies, we have examined their presence in the rat ovary and compared the changes in both uPA and uPAR expression with those of tPA and PAI-1 during follicular growth in vivo. The presence of these proteins in various follicular cells at different stages of maturation was evaluated by immunolocalization and ELISA. Abundance of respective messenger RNA in granulosa cells from preantral/early antral, midantral and preovulatory follicles and the residual ovaries was determined by Northern blot analysis. Whereas uPA transcript and protein levels were highest at the earliest stage of follicular growth examined and decreased markedly before the expected time of ovulation, the opposite was true for uPAR. In addition, tPA and PAI-1 messenger RNA abundance and protein contents were low in both granulosa and residual ovarian tissue during early follicular development but increased thereafter, reaching highest levels at the preovulatory period. These findings demonstrate for the first time the presence of uPAR in ovarian follicles and its developmental expression. The coincidental rise in uPAR and PAI-1 proteins during the preovulatory period may be important for the regulation of extracellular matrix remodelling before ovulation. The reciprocal expression of uPA and tPA during follicular development are consistent with the notion that these proteases have different biological functions in the ovary, i.e. tPA is involved in follicular wall remodelling before ovulation whereas uPA is important in extracellular matrix degradation during cell proliferation and migration that accompany follicle growth.

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