title: Oocytes use the plasminogen-plasmin system to remove supernumerary spermatozoa.
abstract: BACKGROUND
  The role of the plasminogen-plasmin (PLG-PLA) system in fertilization is unknown, although its dysfunction has been associated with subfertility in humans. We have recently detected and quantified plasminogen in the oviductal fluid of two mammals and showed a reduction in sperm penetration during IVF when plasminogen is present. The objective of this study was to describe the mechanism by which PLG-PLA system regulates sperm entry into the oocyte.
  
  
  RESULTS
  By combining biochemical, functional, electron microscopic, immunocytochemical and live cell imaging methods, we show here that (i) plasminogen is activated into the protease plasmin, by gamete interaction; (ii) urokinase-type and tissue-type plasminogen activators are present in oocytes, but they are not of cortical granule origin; (iii) sperm binding to oocytes triggers the releasing of plasminogen activators and (iv) the generated plasmin causes sperm detachment from the zona pellucida.
  
  
  CONCLUSIONS
  Our results describe a novel mechanism for the success or failure of fertilization in mammals, by which molecules present in the oviductal environment are activated by molecules originating within the gametes. We anticipate that therapeutic up- or down-regulation of this physiological mechanism may be used to help in conception or as a contraceptive tool. Since components of the PLG-PLA system are already available as drugs for heart attacks or cancer therapies, basic research on this novel function would be rapidly transferable for clinical application.
authors.affiliation: Physiology of Reproduction Group, Departamento de Fisiología, Universidad de Murcia, Campus Mare Nostrum, Murcia 30071, Spain. pcoy@um.es
authors.forename: Pilar
authors.initials: P
authors.lastname: Coy
authors.forename: María
authors.initials: M
authors.lastname: Jiménez-Movilla
authors.forename: Francisco A
authors.initials: FA
authors.lastname: García-Vázquez
authors.forename: Irene
authors.initials: I
authors.lastname: Mondéjar
authors.forename: Luis
authors.initials: L
authors.lastname: Grullón
authors.forename: Raquel
authors.initials: R
authors.lastname: Romar
mesh_terms: D000818:Animals; D005260:Female; D005306:Fertilization / Q000502:physiology*; D005307:Fertilization in Vitro; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008854:Microscopy, Electron / Q000379:methods; D008954:Models, Biological; D009865:Oocytes / Q000166:cytology*; D010053:Ovary / Q000378:metabolism; D010057:Oviducts / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D013094:Spermatozoa / Q000378:metabolism / Q000473:pathology*; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D015044:Zona Pellucida / Q000378:metabolism
chemical_list: D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator