Tissue-Type Plasminogen Activator and Its Inhibitor Plasminogen Activator Inhibitor Type 1 Are Coordinately Expressed during Ovulation in the Rhesus Monkey

Abstract

Ovulation is a gonadotropin-controlled process that is essential for the propagation of all mammalian species. In the present study, we used a pregnant mare serum gonodotropin/human chorionic gonadotropin (hCG)-induced, synchronized ovulation model in rhesus monkeys and systematically investigated the roles of the plasminogen activator (PA) system in the ovulatory process of the primate. At different follicular developmental stages throughout the periovulatory period, samples of ovaries, granulosa cells, and theca-interstitial cells as well as follicular fluid were collected, and levels of PA and PA inhibitor type-1 (PAI-1) were evaluated by fibrin overlay, reverse fibrin overlay, Northern blot analysis, and in situ hybridization, respectively. We showed that in response to an injection of ovulation-triggering hCG, which mimics the preovulatory surge of LH in the circulation, granulosa cell-derived tissue-type PA (tPA) was substantially elevated in preovulatory follicles and reached its maximum level just before ovulation. Although theca-interstitial cell-derived PAI-1 was also stimulated by pregnant mare serum gonodotropin and hCG treatments, however, the maximum level of PAI-1 appeared 12 h earlier than that of tPA. When ovulation approached, accompanying the highest tPA level in the preovulatory follicles, the follicular PAI-1 level declined dramatically to its minimum value. Moreover, our data on the expression of follicular PA and PAI-1 over the periovulatory period were reinforced by results obtained at the mRNA level. Our data suggest that the coordinated expression of tPA and PAI-1 may be of importance for the follicular rupture process during ovulation in the primate.

Extracellular matrix in ovarian follicular development and disease

“…mRNA for plasminogen activator inhibitor-1 (PAI-1) has been found in the thecal and stromal tissue surrounding the follicle with its highest expression occurring 6 h prior to ovulation (Ny et al 1993). PAI is localised to the theca interna in the rat (Hasan et al 2002) and monkey (Liu et al 2004) ovary and to the granulosa and theca cells in the human ovary (Atiomo et al 2000) and co-localises with aHSPG in the ovulated follicle (Hasan et al 2002).…”

Temporal and spatial expression of MMP-2,-9,-14 and their inhibitors TIMP-1,-2,-3 in the corpus luteum of the cycling rhesus monkey

“…At the early stage of CL development (3-5 d after hCG injection), uPA, but not tPA, is the only active PA species that is identified in the CL. However, during luteolysis when serum progesterone levels and StAR mRNA expression in the CL declined dramatically on D13 after hCG injection [33] , a substantial elevation in tPA mRNA, which is in agreement with corresponding increased tPA activity [14] , was observed, implying that tPA might be a luteolytic factor. Most interesting of all, just prior to the increment of both tPA mRNA and activity levels in the monkey CL at the time of initiation of luteolysis, a peak level of PAI-1 mRNA was measured.…”

“…In our previous studies, using a PMSG / hCG induced luteinized rhesus monkey model, we have demonstrated the involvement of PA/PAI-1 system in controlling CL development [14,33] . At the early stage of CL development (3-5 d after hCG injection), uPA, but not tPA, is the only active PA species that is identified in the CL.…”

“…In the present study we have examined the stage-dependent expression and regulation of MMP-2, -9, -14 and TIMP-1, -2, -3 in the CL of cycling rhesus monkeys throughout the CL lifespan. Based on our previous studies on this species [14,33] we have well designed experiments to define the three stages of CL development, representing the early stage of D5 (CL formation), the middle stage of D10 (CL functional maintaining) and the late stage of D15 (CL regression) at the luteal phase of the normal cycling rhesus monkeys.…”

Mitogen-activated protein kinase regulates FSH-induced expression of tissue-type plasminogen activator through an activator protein 1 response element

“…Two types of PA, tissue-type PA (tPA) and urokinase-type PA (uPA), and a PA inhibitor, PAI-1, have been reported in rat [4] and monkey [5] ovaries. Our previous studies have demonstrated that GCs and oocyte of rat and rhesus monkey produced tPA, while theca cells produced PAI-1, the coordinated expression of tPA and PAI-1 regulated by gonadotrophins in the ovary-induced ovulation [6,7]. Evidence has also shown that rat GCs in vitro express tPA in response to FSH, LH, GnRH, VIP, and growth factors via different signaling pathways [4,[8][9][10][11][12].…”