Roles of proteases and prostaglandins in follicle rupture during ovulation in the medaka

摘要

Ovulation is the process of liberating oocytes from the preovulatory follicles and is observed in the ovaries of virtually all vertebrate female animals. Compared with mammalian species, there have been much fewer studies that address the ovulatory mechanisms of non-mammalian species. We have examined the molecular mechanism of follicle rupture during ovulation using the teleost medaka, Oryzias latipes. Follicle rupture in medaka ovulation involves the cooperative actions of at least three matrix metalloproteinases (MMPs). Our studies also indicate that the serine protease, i.e., plasmin, participates in the rupture prior to the activation of MMP-mediated hydrolysis at ovulation. The mechanism for the rupture is as follows: In the first step of extracellular matrix (ECM) hydrolysis, active plasmin is produced by the proteolytic processing of liver-derived precursor plasminogen in the preovulatory follicle that is destined to ovulate. Active plasmin hydrolyzes laminin, a major ECM component constituting the basement membrane. Laminin degradation by plasmin occurs between 7 to 3 h before ovulation. As a second step, approximately 0-3 h before ovulation, another proteolytic system involving MT1-MMP, MT2-MMP and gelatinase A is activated for further ECM degradation events. Gelatinase A, which is activated by MT1-MMP, hydrolyzes type IV collagen, a principle component of the basement membrane, and MT2-MMP degrades the type I collagen present in the theca cell layer. The involvement of prostaglandin E_2 (PGE_2) in medaka ovulation was demonstrated. Cyclooxygenase-2 and PGE_2 receptor subtype EP4b were shown to be an enzyme responsible for PGE_2 synthesis and a receptor for the generated ligand in the preovulatory follicles, respectively.