Kong Hyun Sun, Lee Jaewang, Youm Hye Won, Kim Seul Ki, Lee Jung Ryeol, Suh Chang Suk, Kim Seok Hyun
Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Gumi-dong, Bundang-gu, Seongnam, Korea.
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
PLoS One. 2017 Sep 15;12(9):e0184546. doi: 10.1371/journal.pone.0184546. eCollection 2017.
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.
卵巢组织（OT）的冷冻保存和移植是一种生育力保存方法。然而，由于移植过程中未进行血管吻合，不可避免地会发生缺血性损伤。为了减少这种缺血性损伤并改善移植后的效果，我们使用了两种血管生成因子，即血管生成素-2（Ang-2）和血管内皮生长因子（VEGF）。制备新鲜或玻璃化复温的牛OT用于异种移植（XT）。将新鲜OT立即异种移植到裸鼠体内（XT-新鲜组）。将玻璃化复温的OT异种移植到四个小鼠亚组中，在XT前腹腔注射生理盐水（XT-玻璃化组）、Ang-2（XT-Ang-2组）、VEGF（XT-VEGF组）以及Ang-2和VEGF的组合（XT-联合组）。移植后7天或28天，收集移植的OT和血液样本进行评估。血管生成因子治疗组的卵泡正常率高于XT-玻璃化组。XT-VEGF组和XT-联合组的卵泡密度高于XT-玻璃化组（P<0.05）。XT-玻璃化组在第7天观察到最高的凋亡卵泡率；XT-联合组的凋亡卵泡率降低（P<0.05）。血管生成因子治疗组的微血管密度高于XT-玻璃化组。XT-玻璃化组在第28天显示出最大的纤维化面积，而XT-联合组的纤维化面积减小（P<0.05）。基于这些结果，在XT前向受体施用Ang-2和VEGF似乎通过增强血管生成来减轻缺血性损伤，从而维持卵泡完整性和密度，并减少卵泡凋亡和OT纤维化。
