Xenotransplantation of whole pig ovaries into nude rats as an experimental model for fertility preservation

Background: Ovarian tissue preservation and retransplantation is a promising strategy to restore fertility in cancer survivors. However, ischemia accompanying ovarian tissue grafting can lead to significant follicle loss. Transplantation of the whole ovary by vascular anastomosis has been considered as an alternative to prevent widespread ischemic damage. In this study the feasibility and function of transplanting whole ovary with intact vasculature were evaluated with the goal of developing a xenograft model for studies using donated human ovaries.

Method: Whole swine ovaries with vascular pedicles were perfused and transplanted as intact ovaries by anastomosis into irradiated ovariectomized nude rats (n = 10). The observation period was between one to four weeks. Fresh swine ovaries served as controls (n = 10). Ovarian stroma and follicle populations were assessed through histological examination.

Result: The majority of transplanted whole ovaries (n = 6) maintained stromal quality and all preantral follicle classes were represented, although follicle numbers decreased compared to fresh control. Four transplanted ovaries were fibrotic after 1 – 4 weeks within the nude rat.

Conclusion: Cryopreservation of whole ovary appears a promising technique in reproductive medicine. However severe follicular loss can be caused by direct cryoinjury to the follicles due to cryotechnology and by ischaemia induced by thromboembolism in the vascular system after transplantation. Therefore the safety and efficacy of the new procedure should be proven before clinical applications take place. Our results demonstrate transplantation of whole pig ovary into nude rats is possible and support development of this xenograft model system for human studies.