Abstract
BackgroundFor women facing gonadotoxic treatment, cryopreservation of ovarian tissue with subsequent retransplantation during remission is a promising technique for fertility preservation. However, follicle loss within grafted ovarian tissue can be caused by ischemia and progressive revascularization. Several xenograft models using different immunodeficient rodent lines are suitable for studying ovarian tissue survival and follicular viability after frozen-thawed ovarian cortex transplantation. SCID mice, which are deficient for functional B and T cells, are the most commonly used mice for ovarian xenograft studies. However, due to incomplete immunosuppression, NOD-SCID mice displaying low NK cell function and an absence of circulating complement might be more appropriate. The present study aims to define the most appropriate immunodeficient mouse strain for ovarian tissue xenotransplantation by comparing ovarian graft recovery in SCID and NOD-SCID mice following engraftment in the presence of isoform 111 of vascular endothelial growth factor.MethodsSheep ovarian cortex fragments were embedded in a collagen matrix, with or without VEGF111, before being stitched onto the ovaries of SCID and NOD-SCID mice. Transplants were recovered after 3 days to study early revascularization or after 3 weeks to evaluate follicle preservation and tissue fibrosis through histological analyses.ResultsAt day 3, vessels were largely reorganized in the ovarian grafts of both mouse strains. After 3 weeks, the cortical tissue was clearly identifiable in SCID mice but not in NOD-SCID mice. Upon VEGF111 treatment, vascularization was significantly improved 3 days after transplantation in SCID mice. This increase in vessel density was correlated with better follicular preservation in SCID mice 3 weeks after transplantation. Fibrosis was not decreased by VEGF treatment in either mouse strain.ConclusionsTissue architecture and follicular morphology were better preserved in ovarian tissues grafted in SCID mice in comparison with NOD-SCID mice. Moreover, tissue revascularization was improved in SCID mice by VEGF111 graft treatment. Thus, we consider SCID mice to be the best murine model for studying ovarian tissue xenografts.
Highlights
For women facing gonadotoxic treatment, cryopreservation of ovarian tissue with subsequent retransplantation during remission is a promising technique for fertility preservation
Graft recovery and histological examination Mice were sacrificed 3 days or 3 weeks after transplantation, and all 102 ovarian xenografts were recovered from the Severe combined immunodeficient (SCID) (n = 32) and Non-Obese Diabetic (NOD)-SCID (n = 19) mice
The overall tissue histology displayed better morphology in SCID compared to NOD-SCID mice
Summary
For women facing gonadotoxic treatment, cryopreservation of ovarian tissue with subsequent retransplantation during remission is a promising technique for fertility preservation. Severe combined immunodeficient (SCID) mice were the first and most commonly used mice for ovarian xenografts [5,8,9] This mouse strain is Fransolet et al Journal of Ovarian Research (2015)8:4 characterized by the scid mutation, which leads to a defect in the recombination of antigen receptor genes, impairing the capacity to generate functional B and T lymphocytes [10,11]. This deficiency contributes to the acceptance of xenogeneic grafts without severe rejection. Based on these multiple defects in innate and adaptive immunity, the NOD-SCID strain is expected to be more promising as a tool for xenotransplantation
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