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将冷冻保存的人卵巢组织异种移植到鼠的背部肌肉中。

Xenotransplantation of cryopreserved human ovarian tissue into murine back muscle.

机构信息

Department of Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.

出版信息

Hum Reprod. 2010 Jun;25(6):1458-70. doi: 10.1093/humrep/deq055. Epub 2010 Mar 18.

Abstract

BACKGROUND

Ovarian tissue (OT) cryopreservation and transplantation are options for fertility preservation in young female cancer patients.

METHODS

We investigated xenotransplantation of human OT into back muscle (B) of severe combined immunodeficiency mice. OT follicle content was evaluated by stereomicroscopy and pre-transplantation. Xenograft survival, follicular development (with/without FSH administration), apoptosis and vascularization were compared in B- versus K-site (under the kidney capsule) several times after grafting using histology, immunohistochemistry and magnetic resonance imaging. In vitro maturation (IVM) was also performed.

RESULTS

Anastomoses which developed from existing human and invading murine vessels were seen in OT at both sites, but angiogenesis was more prominent at the B- than K-site (P < 0.001). Vascularization and follicle size were correlated in the B-group (Spearman's coefficient 0.73; P < 0.001). FSH increased early (8 days) micro-vessel formation in B but not in K grafts (P < 0.0001, versus no FSH). B-site grafts showed a better histological morphology and survival (P = 0.0084), formation of larger antral follicles (P = 0.005), more metaphase-II (MII) oocytes, growing follicles (P = 0.028) and slightly fewer apoptotic follicles than K grafts. One MI oocyte from B underwent IVM and reached MII stage next day.

CONCLUSIONS

To our knowledge, this is the first report of MII and IVM-MII oocytes obtained from B xenografts. We report the largest oval-shaped antral follicles containing an MII oocyte obtained after OT xenotransplantation to date. Xenografting in the mouse B should be further explored as a method for human OT transplantation.

摘要

背景

卵巢组织(OT)冷冻保存和移植是年轻女性癌症患者生育力保存的选择。

方法

我们研究了将人类 OT 异种移植到严重联合免疫缺陷小鼠的背部肌肉(B)中。通过体视显微镜和移植前评估 OT 卵泡含量。使用组织学、免疫组织化学和磁共振成像在移植后多次比较 B 位(肾脏囊下)与 K 位(肾包膜下)的异种移植物存活、卵泡发育(有无 FSH 给药)、细胞凋亡和血管生成。还进行了体外成熟(IVM)。

结果

在两个部位的 OT 中均可见从现有人和入侵的鼠血管发育而来的吻合,但 B 位的血管生成比 K 位更为明显(P < 0.001)。B 组的血管生成与卵泡大小呈正相关(Spearman 系数 0.73;P < 0.001)。FSH 可在 8 天内早期增加 B 位而非 K 位的微血管形成(P < 0.0001,与无 FSH 相比)。B 位移植物显示出更好的组织学形态和存活率(P = 0.0084)、形成更大的窦卵泡(P = 0.005)、更多的中期 II(MII)卵母细胞、生长卵泡(P = 0.028)和略少的凋亡卵泡比 K 位移植物。一个来自 B 的 MI 卵母细胞经历了 IVM,并在第二天达到 MII 阶段。

结论

据我们所知,这是首次报道从 B 异种移植物中获得 MII 和 IVM-MII 卵母细胞。我们报告了迄今为止从 OT 异种移植中获得的最大椭圆形窦卵泡,其中含有一个 MII 卵母细胞。应该进一步探索小鼠 B 位的异种移植作为人类 OT 移植的方法。

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