title: Review of the role of the plasminogen activator system and vascular endothelial growth factor in subfertility.
abstract: OBJECTIVE
  To assess the importance of the plasminogen activator (PA) system and vascular endothelial growth factor (VEGF) in subfertility.
  
  
  METHODS
  Review.
  
  
  METHODS
  Two university IVF centers.
  
  
  METHODS
  Systematic literature search (MEDLINE, Science Direct, and bibliographies of published works).
  
  
  RESULTS
  The PA system in the male is involved in the passage of spermatozoa precursor cells over the blood-testis barrier, the epididymal maturation of spermatozoa, the modifications of the sperm surface for capacitation, the acrosome reaction and zona pellucida attachment, and finally the facilitation of spermatozoa to move into the fallopian tubes. In the female, the PA system plays a role during ovulation in the release of the oocyte from the follicle, the facilitation of oocyte movement into the fallopian tubes, and the extracellular matrix degradation important for angiogenesis in the ovary. The function of VEGF during fertilization is largely unknown. It has been suggested that VEGF is important for the fluid and proteins in semen and fluid secretion in the female genital tract, thereby influencing sperm motility and survival. The latter could be due to an effect of VEGF on testicular microvasculature, through which an adequate microenvironment for spermatogenesis is provided. In the female, VEGF is involved in the regulation of the cyclic ovarian angiogenesis, the development and/or selection of follicles, the accumulation of follicular fluid, and corpus luteum angiogenesis.
  
  
  CONCLUSIONS
  The role of the PA system and VEGF in reproduction most likely is of great interest. However, much of the data are derived from experimental animal studies. So far, information on the importance of these systems in humans is scarcely investigated. Therefore, further research is required to elucidate the role of the PA system and VEGF in the pathogenesis and prevention of male and female subfertility. Eventually, this will contribute to the improvement of the diagnosis of subfertility and may possibly lead to targeted therapeutic management of subfertility.
authors.affiliation: Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Inge M W
authors.initials: IM
authors.lastname: Ebisch
authors.forename: Chris M G
authors.initials: CM
authors.lastname: Thomas
authors.forename: Alex M M
authors.initials: AM
authors.lastname: Wetzels
authors.forename: Wim N P
authors.initials: WN
authors.lastname: Willemsen
authors.forename: Fred C G J
authors.initials: FC
authors.lastname: Sweep
authors.forename: Régine P M
authors.initials: RP
authors.lastname: Steegers-Theunissen
mesh_terms: D000818:Animals; D005260:Female; D005306:Fertilization; D006801:Humans; D007247:Infertility, Female / Q000378:metabolism* / Q000503:physiopathology; D007248:Infertility, Male / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D018919:Neovascularization, Physiologic; D010060:Ovulation; D010960:Plasminogen Activators / Q000378:metabolism*; D013091:Spermatogenesis; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism*
chemical_list: D042442:Vascular Endothelial Growth Factors; D010960:Plasminogen Activators