Abstract

Cryopreservation and transplantation of ovarian tissue (OT) represents a method for fertility preservation. However, as the transplantation is performed without vessel anastomosis, unavoidable ischemic damage occurs. To reduce this ischemic damage and improve outcomes after transplantation, we used two kind of angiogenic factors, angiopoietin-2 (ang-2) and vascular endothelial growth factor (VEGF). Fresh or vitrified-warmed bovine OTs were prepared for xenotransplantation (XT). Fresh OTs were immediately xenografted into nude mice (XT-Fresh). Vitrified-warmed OTs were xenografted into four subgroups of mice, which were injected intraperitoneally before XT with saline (XT-Vitri), Ang-2 (XT-Ang-2), VEGF (XT-VEGF), and a combination of Ang-2 and VEGF (XT-Combined). Seven or 28 days post-grafting, grafted OTs and blood samples were collected for evaluation. Follicle normality was higher in the angiogenic factor-treated groups than in the XT-Vitri group. The XT-VEGF and the XT-Combined showed higher (P<0.05) follicular density than the XT-Vitri group. The highest apoptotic follicle ratio was observed in the XT-Vitri group on day 7; this was decreased (P<0.05) in the XT-Combined group. Microvessel densities were higher in the angiogenic factor-treated groups than in the XT-Vitri group. The largest fibrotic area was showed in the XT-Vitri group on day 28, and it was decreased (P<0.05) in the XT-combined group. Based on these results, administration of Ang-2 and VEGF to recipients prior to XT appeared to alleviate ischemic damage by enhancing angiogenesis, which resulted in the maintenance of follicle integrity and density, and reduced follicle apoptosis and OT fibrosis.

Highlights

  • Advances in cancer therapy have improved survival outcomes in patients with cancer

  • Angiogenic factors Ang-2 and/or vascular endothelial growth factor (VEGF) were injected into recipient mice to enhance angiogenesis and reduce ischemic injury following the XT of avascular bovine ovarian tissue (OT)

  • The exact half-life of VEGF164 used in this study is not known, but VEGF is known to have short half-life [34]

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Summary

Introduction

Advances in cancer therapy have improved survival outcomes in patients with cancer. reduced fertility, with premature ovarian failure, is often observed in young women following treatment for cancer [1, 2]. Numerous studies have attempted to determine the most suitable grafting site [11, 12], optimal ovarian cortex size [3], and to identify effective treatment substances for enhancement of neovascularization to achieve OT graft survival and restore ovarian function [13,14,15,16]. Optimization of this technique is still necessary to improve outcomes following transplantation

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