Fertile offspring derived from mouse spermatogonial stem cells cryopreserved for more than 14 years

由冷冻保存超过14年的小鼠精原干细胞衍生的可育后代

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作者:Xin Wu ,Shaun M Goodyear, Lara K Abramowitz, Marisa S Bartolomei, John W Tobias, Mary R Avarbock, Ralph L Brinster

Abstract

Background: Approximately 80% of childhood cancers can now be cured but a side effect of treatment results in about one-third of the surviving boys being infertile or severely subfertile when they reach reproductive age. Currently, more than 1 in 5000 men of reproductive age who are childhood cancer survivors suffer from this serious quality of life problem. It is possible to obtain a testicular biopsy before treatment to preserve the spermatogonial stem cells (SSCs) of the male by cryopreservation, but the results of long-term storage of SSCs on their subsequent functional ability to generate normal offspring has not been examined in any mammalian species. Moreover, it will be necessary to increase the number of these cryopreserved SSCs to remove any contaminating malignant cells and assure regeneration of spermatogenesis. Methods and results: In this report, we demonstrate that long-term cryopreservation (>14 years) of testis cells from mouse, rat, rabbit and baboon safeguards SSC viability, and that these cells can colonize the seminiferous tubules of recipient testes. Moreover, mouse and rat SSCs can be cultured and re-establish complete spermatogenesis, and fertile mouse progeny without apparent genetic or epigenetic errors were generated by the sperm produced. Conclusions: These findings provide a platform for fertility preservation in prepubertal boys undergoing gonadotoxic treatments.

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