1 Ovarian Membrane Type Matrix Metalloproteinases: Induction of MMP14 and MMP16 during the Periovulatory Period in the Rat, Macaque, and Human1 Short Title: Ovarian MT-MMP Expression during the Periovulatory Period

An intrafollicular increase in proteolytic activity drives ovulatory events. Surprisingly, the periovulatory expression profile of the membrane type-matrix metalloproteinases (MT-MMPs), unique proteases anchored to the cell surface, has not been extensively examined. Expression profiles of the MT-MMPs were investigated in ovarian tissue from well-characterized rat and macaque periovulatory models and naturally cycling women across the periovulatory period. Among the six known MT-MMPs, mRNA expression of Mmp14, Mmp16 and Mmp25 was increased after hCG in the rat. In human granulosa cells, mRNA expression of MMP14 and MMP16 increased following hCG treatment. In contrast, mRNA levels of MMP16 and MMP25 in human theca cells were unchanged prior to ovulation but declined by the post-ovulatory stage. In macaque granulosa cells, hCG increased mRNA for MMP16 but not MMP14. Immunoblotting showed that protein levels of MMP14 and MMP16 in the rat increased similar to their mRNA expression. In macaque granulosa cells, only the active-form of the MMP14 protein increased after hCG unlike its mRNA or the pro-protein. By immunohistochemistry both MMP14 an