Proteolytic Mechanisms in the Ovulatory Folliculo-Luteal Transformation

The connective tissue matrix of the wall of ovarian follicles is degraded and remodeled during ovulatory rupture and formation of the corpus luteum. Ovarian surface epithelial cells in close contact with the apical wall of preovulatory ovine follicles secrete a urokinase-type plasminogen activator in response to surge levels of gonadotropins. Urokinase activates latent collagenases and stimulates release of tumor necrosis factor &#102 from thecal endothelium. Tumor necrosis factor &#102 progressively induces matrix metalloproteinase gene expression, apoptosis, and inflammatory necrosis. Collagenolysis and cellular death are a prelude to stigma formation and ovarian rupture. Ovulation is blocked by intrafollicular injection of TNF &#102 or MMP-2 antisera. Unruptured follicles luteinize but are deficient in collagenous/vascularized trabeculae, and produce less progesterone than their control luteal counterparts. It appears that TNF &#102 , via MMP-2 induction, contributes to the reorganization of an ovulatory follicle into a fully competent corpus luteum.