Relationship Between Release of Plasminogen Activator and Estrogen by Blastocysts and Secretion of Plasmin Inhibitor by Uterine Endometrium in the Pregnant Pig

Abstract

Pig blastocysts isolated between Days 10 and 16 of pregnancy release the protease, plasminogen activator (PA), into the medium in a time-dependent manner when cultured in vitro. Production is biphasic. The initial phase (Days 10-12) coincides with the early elongation stages, while release during the second phase (Days 14-16) occurs during a time at which the DNA content of the blastocysts is increasing markedly. Uterine flushings from these pregnant animals contain the zymogen substrate for PA, plasminogen, presumably as a serum transudate. Plasminogen is present in highest amounts at Day 12. The blastocyst, therefore, has the potential ability to generate the broadly specific protease, plasmin, within the uterine lumen. However, during this same period, the endometrium secretes an inhibitor of plasmin into the uterine lumen. In pregnant animals the amount of plasmin inhibitory activity rose 7-fold between Day 10.5, when the blastocysts were spherical, and Day 12, when they had become filamentous. At Day 12 each uterine horn contained about 3 to 4 mg of plasmin inhibitor. A similar release of inhibitor can be initiated in nonpregnant gilts given a single, intramuscular injection of estradiol valerate on Day 11 of the estrous cycle. It is suggested that the initiation of estrogen production by the elongating blastocyst triggers the release of plasmin inhibitor by the maternal endometrium and that the inhibitor serves to prevent a proteolytic cascade of reactions initiated by blastocyst PA, which might otherwise damage the uterine epithelium.

Development and survival of pig blastocysts after oestrogen administration on Day 9 or Days 9 and 10 of pregnancy

“…Decreased staining intensity of uteroferrin was also reflected by the lower acid phosphatase activity and specific acid phosphatase activity from uterine flushings of oestradiol-treated gilts (Table 3). Although oestradiol administration had no effect on the uterine content of the plasmin inhibitors (Table 4), staining intensity of the low molecular weight (MT14 000) plasmin isoinhibitors (Fazleabas et al, 1983) appeared to be decreased (Fig. 3b).…”

Integrins and Extracellular Matrix Proteins at the Maternal-Fetal Interface in Domestic Animals

“…Mechanisms responsible for activation of latent TGFßs at the maternal-conceptus interface are not known, however, porcine conceptuses produce plasminogen activator [Fazleabas et al,1983] and other proteases which could effect activation at the apical aspect of the Tr. As noted previously, expression of OPN, oFN and several integrin subunits identified at the porcine maternal-conceptus interface may be upregulated by active TGFßs during the peri-implantation period [Rider and Piva, 1998].…”

“…Likewise, cathepsin-L proteolytic activity and protein has been detected in endometrial GE and uterine flushings from early implanting pigs . Urokinasetype plasminogen activator (uPA) is produced by mouse [Strickland et al, 1976], pig [Fazleabas et al, 1983] and ovine [Bartlett and Menino, 1993] embryos, and has been postulated to play a role in implantation of blastocysts into the rodent uterus [Sappino et al, 1989]. Further, the uPA receptor interacts with uPA and integrins to both facilitate a proteolytic cascade at the cell surface, and initiate signaling events that contribute to cell adhesive processes in a non-proteolytic manner [Ossowski and Aguirre-Ghiso, 2000;Preissner et al, 2000].…”

Enhancement of hatching and trophoblastic outgrowth by mouse embryos cultured in Whitten's medium containing plasmin and plasminogen

“…Although the zona lysin may be a uterine-specific product, plasma transudates of zymogens or enzymes may also be involved since oestrogen-induced uptake of plasminogen by the mouse uterus has been reported (Finlay et ai, 1983). Embryos are capable of producing plasminogen activator Fazleabas, Geisert, Bazer & Roberts, 1983) and the presence of uterine plasminogen serves as a convenient source of protease which the embryo is capable of activating to plasmin and possibly utilizing for either hatching or implantation. In an effort to examine the effects of plasmin and its zymogen, plasminogen, a simple embryo culture medium was supplemented with these proteins and subsequent embryonic development was compared with that in unsupplemented medium, media with trypsin or pronase, and medium with serum.…”