Implications of decidualization-associated protease expression in implantation and menstruation.

摘要: During progesterone-induced decidualization of estradiol (E2)-primed human endometrial stromal cells (HESCs), the interstitial-type extracellular matrix (ECM) follicular phase endometrium is transformed in luteal to a mixture residual interstitial- and new basal laminar-type components. This transformation accelerated by reduced proteolytic activity HESCs undergoing (DZ). In cultured HESCs, progestins, but not E2, induce expression several DZ markers, E2 enhances these effects despite lack response alone. Using this well-characterized vitro model we evaluated plasminogen activators (PAs), which degrade ECM components that undergo rapid turnover, metalloproteinases (MMPs), bulk Medroxyprogesterone acetate (MPA) inhibited catalytic urokinase-type PA (uPA) tissue-type (tPA) as well such MMPs interstitial collagenase (MMP-1) stromelysin-1 (MMP-3). Moreover, + MPA elicited greater inhibitory on all proteases. Progestin inhibition activities reflected reciprocal upregulation output inhibitor PAI-1, produced large molar excesses PAI-1 compared with PAs HESC-conditioned medium. By contrast, tissue MMPs, TIMP1, gelatinase A (MMP-2), was constitutively expressed HESCs. absence implantation, menstruation-associated degradation functional triggered withdrawal circulating ovarian steroids. process were first decidualized during 10 days exposure MPA, then withdrawn steroid-free medium without antiprogestin RU 486. As expected, steroid reversed progestin-inhibited MMP-1 MMP-3 progestin-enhanced PAI-1; much reversal observed supplemented Unlike changes neither nor MMP-2 affected or 486-medium. altering composition endometrium, progestin-elicited PAs, uPA tPA, MMP-3, modulates trophoblast adhesion, migration differentiation. Conversely, increases uPA, would promote sloughing degrading decidual cell-derived basement membrane-like proteins comprise perimenstrual endometrium.