title: Isoform 111 of vascular endothelial growth factor (VEGF111) improves angiogenesis of ovarian tissue xenotransplantation.
abstract: BACKGROUND
  Cryopreservation of cortex ovarian tissue before anticancer therapy is a promising technique for fertility preservation mainly in children and young women. Ischemia in the early stage after ovarian graft causes massive follicle loss by apoptosis. VEGF111 is a recently described vascular endothelial growth factor (VEGF) isoform that does not bind to the extracellular matrix, diffuses extensively, and is resistant to proteolysis. These properties confer a significantly higher angiogenic potential to VEGF111 in comparison with the other VEGF isoforms.
  
  
  METHODS
  We evaluated the morphology of cryopreserved sheep ovarian cortex grafted in the presence or absence of VEGF111. Ovarian cortex biopsies were embedded in type I collagen with or without VEGF111 addition before transplantation to severe combined immunodeficient mice ovaries. Transplants were retrieved 3 days or 3 weeks later. Follicular density, vasculature network, hemoglobin content, and cell proliferation were analyzed.
  
  
  RESULTS
  Addition of VEGF111 increased density of functional capillaries (P=0.01) 3 days after grafting. By double immunostaining of Ki-67 and von Willebrand factor, we demonstrated that proliferating endothelial cells were found in 83% of the VEGF111 group compared with 33% in the control group (P=0.001). This angiostimulation was associated with a significant enhancement of hemoglobin content (P=0.03). Three weeks after transplantation, the number of primary follicles was significantly higher in VEGF111 grafts (P=0.02).
  
  
  CONCLUSIONS
  VEGF111 accelerates blood vessel recruitment and functional angiogenesis and improves the viability of ovarian cortex by limiting ischemia and ovarian cortex damage.
authors: Laboratory of Tumor and Development Biology, Groupe Interdisciplinaire de Génoprotéomique Appliqué (GIGA-R), Université de Liège, Liège, Belgium. soraya.labied@ulg.ac.be
authors: Soraya
authors: S
authors: Labied
authors: Yves
authors: Y
authors: Delforge
authors: Carine
authors: C
authors: Munaut
authors: Silvia
authors: S
authors: Blacher
authors: Alain
authors: A
authors: Colige
authors: Romain
authors: R
authors: Delcombel
authors: Laurie
authors: L
authors: Henry
authors: Maïté
authors: M
authors: Fransolet
authors: Caroline
authors: C
authors: Jouan
authors: Sophie
authors: S
authors: Perrier d'Hauterive
authors: Agnès
authors: A
authors: Noël
authors: Michelle
authors: M
authors: Nisolle
authors: Jean-Michel
authors: JM
authors: Foidart
mesh_terms: D000818:Animals; D017209:Apoptosis; D001706:Biopsy; D049109:Cell Proliferation / Q000187:drug effects; D015925:Cryopreservation; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D051379:Mice; D016513:Mice, SCID; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D006080:Ovarian Follicle / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D010053:Ovary / Q000098:blood supply* / Q000473:pathology / Q000637:transplantation*; D020033:Protein Isoforms; D012756:Sheep; D014183:Transplantation, Heterologous / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A