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Morphometrical analysis of preantral follicular survival of VEGF-treated bovine ovarian cortex tissue following xenotransplantation in an immune deficient mouse model

Langbeen, A., Ginneken, C. Van, Fransen, E., Bosmans, E., Leroy, J.L.M.R., Bols, P.E.J.
Animal reproduction science 2016 v.168 pp. 73-85
animal models, animal ovaries, blood coagulation factors, caspase-3, cattle, cortex, ethics, female fertility, females, humans, mice, neoplasms, vascular endothelial growth factors, xenotransplantation
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.