Involvement of the Plasminogen Activator/Plasmin Proteolytic Cascade in Fertilization

Huarte, Joaquín; Vassalli, Jean‐Dominique; Belin, Dominique; Sakkas, Denny

doi:10.1006/dbio.1993.1156

Cited by 55 publications

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“…In situ hybridization experiments revealed that expression of uPA mRNA was mainly localized to granulosa cells of preovulatory follicles, whereas tPA mRNA was mainly localized to oocytes and thecainterstitial tissue including apical regions of the preovulatory follicles that are located on the surface region of the ovary (ref. (21)(22)(23)(24)(25)(26)(27)(28). The reduced fertility observed in mice with a combined deficiency of tPA and uPA could therefore be due to a defect in any of these biological processes; alternatively, it could be caused by the general health problems associated with the double-deficient genotype, which is manifested in growth retardation beyond the age of 3 weeks and the onset of several pathological conditions from the age of 8-12 weeks (20).…”

Section: Resultsmentioning

confidence: 99%

“…In addition to ovulation, successful reproduction involves several proteolytic processes where the PA system has been suggested to play a pivotal role including fertilization, embryo implantation, and embryogenesis (21)(22)(23)(24)(25)(26)(27)(28) Analysis of DNA and RNA. Genomic DNA was isolated from mouse tail tips and genotyped by Southern blot analysis as described (19,20).…”

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confidence: 99%

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Ovulation efficiency is reduced in mice that lack plasminogen activator gene function: functional redundancy among physiological plasminogen activators.

Leonardsson

Peng

Liu

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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Several lines of indirect evidence suggest that plasminogen activation plays a crucial role in degradation of the follicular wall during ovulation. However, single-deficient mice lacking tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), or PA inhibitor type 1 (PAI-1) gene function were recently found to have normal reproduction, although mice with a combined deficiency of tPA and uPA were significantly less fertile. To investigate whether the reduced fertility of mice lacking PA gene function is due to a reduced ovulation mechanism, we have determined the ovulation efficiency in 25-day-old mice during gonadotropin-induced ovulation. Our results reveal that ovulation efficiency is normal in mice with a single deficiency of tPA or uPA but reduced by 26% in mice lacking both physiological PAs. This result suggests that plasminogen activation plays a role in ovulatory response, although neither tPA nor uPA individually or in combination is obligatory for ovulation. The loss of an individual PA seems to be functionally complemented by the remaining PA but this compensation does not appear to involve any compensatory up-regulation. Our data imply that a functionally redundant mechanism for plasmin formation operates during gonadotropin-induced ovulation and that PAs together with other proteases generate the proteolytic activity required for follicular wall degradation.Proteolysis generated by the plasminogen activator (PA)/ plasmin system has been associated with many physiological and pathological processes such as ovulation, embryo implantation and embryogenesis, mammary involution, fibrinolysis, angiogenesis, inflammation, and tumor invasion (1-3).In mammals, ovulation is triggered by the preovulatory surge of luteinizing hormone from the pituitary, which results in liberation of the mature oocyte from the preovulatory ovarian follicle into the periovulatory space (4). A mature follicle destined to ovulate usually protrudes on the surface of the ovary. For the ovum to escape from this structure, an extensive proteolytic degradation of basement membranes and the connective tissue that constitute the follicle wall is required. Several lines of indirect evidence suggest that the PAs together with matrix metalloproteinases (MMPs) play a role in follicular rupture (for review, see refs. 5-7).

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Ovulation efficiency is reduced in mice that lack plasminogen activator gene function: functional redundancy among physiological plasminogen activators.

Leonardsson

Peng

Liu

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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“…tPA is expressed by mouse oocytes during maturation (Huarte et al 1995) and has been proposed to play a role in preventing polyspermy and other events during fertilisation (Zhang et al 1992;Huarte et al 1993). tPA is not expressed beyond the two-cell stage in the mouse (Zhang et al 1994).…”

Section: Introductionmentioning

confidence: 99%

Urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) expression and activity during early embryo development in the cow

Whiteside

Kan

Jackson

et al. 2001

Anatomy and Embryology

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Several extracellular matrix (ECM)-degrading proteinases are hypothesised to play important roles during early mammalian development. In particular, urokinase-type plasminogen activator (uPA) and matrix metalloproteinase 9 (MMP-9) are expressed in peri-implantation mouse, sheep, and pig embryos and are implicated in the implantation process. These proteinases are not expressed in early (pre-blastocyst) mouse, sheep or pig embryos. The aim of this study was to establish the gene expression and proteolytic activity of uPA and MMP-9 in in vitro-produced (IVP) cow embryos. Using RT-PCR, mRNA transcripts for uPA and MMP-9 were detected during the first 7 days of development. To investigate the activity of these proteinases, conditioned media from various stages of development (days 2, 3, 4, 5 and 7) were assayed for uPA activity by chromogenic assay and MMP-9 activity by gelatin zymography. Both uPA and MMP-9 activities were detected in the media samples indicating the production and secretion of these proteinases. This pattern of proteinase expression is novel in comparison to the mouse where uPA and MMP-9 are only expressed from the blastocyst stage onwards. The results of this study suggest that these ECM proteinases have a role prior to implantation in the cow, in contrast to that exhibited by mouse, sheep and pig embryos.

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“…Our results provide conclusive evidence that uPAR is synthesized by germ cells during spermatogenesis, and that it is present on spermatids and mature mouse spermatozoa. Together with the previously described presence of plasminogen-binding sites on these cells [13], these observations raise the question of the possible role(s) of the uPA-plasminogen system in spermatogenesis, spermatozoa maturation and/or fertilization. …”

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confidence: 58%

“…Extracellular proteolysis could also facilitate the migration of spermatozoa towards the ampula, by preventing their adhesion to fibrin deposits on the tubal mucosa [23]. The binding of plasminogen to mouse spermatozoa and its positive effect on in vitro fertilization of mouse gametes [13] and the presence of plasminogen in the uterine lumen [24] suggest that uPAR-bound uPA could be involved in fertilization. Taken together, these observations raise the possibility that the uPAR may play a role at one or more step(s) from spermatogenesis to fertilization.…”

Section: Discussionmentioning

confidence: 99%

The receptor for urokinase‐type plasminogen activator is expressed during mouse spermatogenesis

Zhou

Vassalli

1997

FEBS Letters

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Key words: uPA receptor; Germ cell; Spermatozoa; Local proteolysis be synthesized by epithelial cells from the caudal part of the epididymis and the vas deferens [10], and the binding of exogenous uPA to spermatozoa prepared from the vas deferens suggested the presence of uPAR [10]. However, because of difficulties in preparing spermatozoa that had not been exposed to epididymal or vas deferens secretions, the evidence for the presence of uPAR on spermatozoa was not unambiguous. We have thus re-investigated this issue, taking advantage of the availability of mice lacking uPA [11] and of molecular probes for murine uPAR mRNA [12]. Our results provide conclusive evidence that uPAR is synthesized by germ cells during spermatogenesis, and that it is present on spermatids and mature mouse spermatozoa. Together with the previously described presence of plasminogen-binding sites on these cells [13], these observations raise the question of the possible role(s) of the uPA-plasminogen system in spermatogenesis, spermatozoa maturation and/or fertilization.

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Involvement of the Plasminogen Activator/Plasmin Proteolytic Cascade in Fertilization

Cited by 55 publications

References 0 publications

Ovulation efficiency is reduced in mice that lack plasminogen activator gene function: functional redundancy among physiological plasminogen activators.

Ovulation efficiency is reduced in mice that lack plasminogen activator gene function: functional redundancy among physiological plasminogen activators.

Urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) expression and activity during early embryo development in the cow

The receptor for urokinase‐type plasminogen activator is expressed during mouse spermatogenesis

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