Follicular growth after xenotransplantation of cryopreserved/thawed human ovarian tissue in SCID mice: dynamics and molecular aspects

冷冻保存/解冻人类卵巢组织异种移植到严重联合免疫缺陷症 (SCID) 小鼠体内后的卵泡生长:动力学和分子方面

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作者:Sarrah Ayuandari, Katharina Winkler-Crepaz, Monika Paulitsch, Cora Wagner, Claudia Zavadil, Claudia Manzl, Stephanie C Ziehr, Ludwig Wildt, Susanne Hofer-Tollinger

Conclusion

The higher proportion of growing follicles compared to resting follicles observed after xenotransplantation is most likely due to downregulation of PTEN gene expression followed by acceleration of follicular recruitment.

Purpose

To study the influence of xenotransplantation on follicular recruitment and growth in cryopreserved/thawed human ovarian tissue. Method: Two 3-mm pieces of cryopreserved/thawed human ovarian tissue obtained from female cancer patients (n = 11) were xenotransplanted into a subcutaneous neck pouch of 6-week-old ovarectomized SCID mice (n = 33) for 4 (n = 18) and 12 (n = 15) weeks. Result: Thirty-two out of 33 mice survived the entire observation periods. Graft recovery rate was 95.58 % (65 of 68 grafts). The percentages of primordial follicles after 4 weeks (P < 0.001) and 12 weeks (P = 0.009) of grafting were significantly lower in comparison to pregraft controls. The percentage of secondary follicle was significantly higher after 4 weeks of grafting (P = 0.018) and after 12 weeks (P = 0.001) of grafting in comparison to pregraft controls. Ki67 immunohistochemistry showed that proliferative follicles were significantly higher after 4 and 12 weeks of grafting compared to pregraft controls (P < 0.001). All follicles analyzed by TUNEL staining appeared healthy after xenotransplantation. The expression level of PTEN was reduced by 2.47-fold after 4 weeks of xenotransplantation, and this result was significant when 2-ΔCt were analyzed (P = 0.042).

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