title: Morphometrical analysis of preantral follicular survival of VEGF-treated bovine ovarian cortex tissue following xenotransplantation in an immune deficient mouse model.
abstract: The increasing number of cancer survivors the past decades, has sparked the need for fertility preservation strategies. Due to predominantly ethical constraints, human research material is scarce. A bovine in vitro model is a valuable alternative. Therefore, the following objectives were defined: 1) to xeno-graft bovine ovarian cortex tissue in immune deficient mice as a study-model for female fertility preservation strategies; 2) to stereologically quantify vascularization in Vascular Endothelial Growth Factor (VEGF)-treated and non-treated tissue; 3) to study preantral follicular survival in situ, after xenotransplantation. Bovine ovarian tissue strips were incubated with or without VEGF prior to grafting into female, neutered BALB/c-nu mice (n=16). Non-transplanted cortical tissue was used as a control. At time zero (control), two (2 weeks) and four (4 weeks) weeks after transplantation, grafts were retrieved and assessed by von Willebrand Factor and caspase-3 immunostaining. Data were analyzed using a linear mixed model. In the VEGF+ grafts, 31% of the follicles were considered 'alive' 2 weeks after transplantation, compared to only 17% in the VEGF- grafts (P<0.05). However, no difference could be detected 4 weeks after transplantation (P=0.76) with less follicles being considered 'alive' after transplantation (22%), compared to the control (47.5%) (P<0.05). Finally, the vascular surface density was significantly less in the grafts, irrespective of the transplantation period or the use of VEGF. Although the transplantation process overall negatively influenced the number of viable follicles and vascular density, VEGF exposure prior to transplantation can favor follicle survival during a 2 weeks transplantation period.
authors.affiliation: University of Antwerp, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Laboratory of Veterinary Physiology and Biochemistry, Universiteitsplein 1, Gebouw U, B-2610 Wilrijk, Belgium. Electronic address: an.langbeen@uantwerpen.be.
authors.forename: A
authors.initials: A
authors.lastname: Langbeen
authors.affiliation: University of Antwerp, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Laboratory of Applied Veterinary Morphology, Universiteitsplein 1, Gebouw U, B-2610 Wilrijk, Belgium.
authors.forename: C Van
authors.initials: CV
authors.lastname: Ginneken
authors.affiliation: StatUa Center for Statistics, University of Antwerp, Prinsstraat 13, B-2000 Antwerp, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Fransen
authors.affiliation: AML (Algemeen Medisch Labo), E. Vloorstraat 9, B-2020 Antwerp, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Bosmans
authors.affiliation: University of Antwerp, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Laboratory of Veterinary Physiology and Biochemistry, Universiteitsplein 1, Gebouw U, B-2610 Wilrijk, Belgium.
authors.forename: J L M R
authors.initials: JLMR
authors.lastname: Leroy
authors.affiliation: University of Antwerp, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Laboratory of Veterinary Physiology and Biochemistry, Universiteitsplein 1, Gebouw U, B-2610 Wilrijk, Belgium.
authors.forename: P E J
authors.initials: PEJ
authors.lastname: Bols
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002417:Cattle; D005260:Female; D006085:Graft Survival; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D006080:Ovarian Follicle / Q000187:drug effects / Q000637:transplantation*; D010053:Ovary / Q000166:cytology / Q000637:transplantation*; D014183:Transplantation, Heterologous / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; D053148:Caspase 3
keywords: Bovine ovarian cortex; Early preantral follicles; Ovarian tissue xenotransplantation; Stereology; Vascular endothelial growth factor