Xiong Jiaqiang, Lu Zhiyong, Wu Meng, Zhang Jinjin, Cheng Jing, Luo Aiyue, Shen Wei, Fang Li, Zhou Su, Wang Shixuan
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Hubei Key Laboratory of Embryonic Stem Cell Research, Tai-He Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
PLoS One. 2015 Oct 2;10(10):e0139824. doi: 10.1371/journal.pone.0139824. eCollection 2015.
Early menopause and infertility often occur in female cancer patients after chemotherapy (CTx). For these patients, oocyte/embryo cryopreservation or ovarian tissue cryopreservation is the current modality for fertility preservation. However, the above methods are limited in the long-term protection of ovarian function, especially for fertility preservation (very few females with cancer have achieved pregnancy with cryopreserved ovarian tissue or eggs until now). In addition, the above methods are subject to their scope (females with no husband or prepubertal females with no mature oocytes). Thus, many females who suffer from cancers would not adopt the above methods pre- and post-CTx due to their uncertainty, safety and cost-effectiveness. Therefore, millions of women have achieved long-term survival after thorough CTx treatment and have desired to rescue their ovarian function and fertility with economic, durable and reliable methods. Recently, some studies showed that mice with infertility caused by CTx can produce normal offspring through intraovarian injection of exogenous female germline stem cells (FGSCs). Though exogenous FGSC can be derived from mice without immune rejection in the same strain, it is difficult to obtain human female germline stem cells (hFGSCs), and immune rejection could occur between different individuals. In this study, infertility in mice was caused by CTx, and the ability of FGSCs to restore ovarian function or even produce offspring was assessed. We had successfully isolated and purified the FGSCs from adult female mice two weeks after CTx. After infection with GFP-carrying virus, the FGSCs were transplanted into ovaries of mice with infertility caused by CTx. Finally, ovarian function was restored and the recipients produced offspring long-term. These findings showed that mice with CTx possessed FGSCs, restoring ovarian function and avoiding immune rejection from exogenous germline stem cells.
早期绝经和不孕在女性癌症患者化疗后常出现。对于这些患者，卵母细胞/胚胎冷冻保存或卵巢组织冷冻保存是目前的生育力保存方式。然而，上述方法在卵巢功能的长期保护方面存在局限，尤其是在生育力保存方面（到目前为止，极少有患癌女性通过冷冻保存的卵巢组织或卵子成功怀孕）。此外，上述方法有其适用范围限制（没有丈夫的女性或未成熟卵母细胞的青春期前女性）。因此，许多患癌女性由于其不确定性、安全性和成本效益，在化疗前后不会采用上述方法。所以，数百万女性在彻底的化疗治疗后实现了长期生存，并渴望通过经济、持久且可靠的方法挽救其卵巢功能和生育力。最近，一些研究表明，化疗导致不孕的小鼠通过卵巢内注射外源性雌性生殖干细胞（FGSCs）可产生正常后代。尽管外源性FGSC可从同一品系无免疫排斥的小鼠中获取，但获取人类雌性生殖干细胞（hFGSCs）困难，且不同个体间可能发生免疫排斥。在本研究中，通过化疗使小鼠产生不孕，评估FGSCs恢复卵巢功能甚至产生后代的能力。我们在化疗后两周成功从成年雌性小鼠中分离并纯化出FGSCs。用携带绿色荧光蛋白的病毒感染后，将FGSCs移植到化疗导致不孕的小鼠卵巢中。最终，卵巢功能得以恢复，受体长期产生后代。这些发现表明，化疗后的小鼠拥有FGSCs，可恢复卵巢功能并避免外源性生殖干细胞的免疫排斥。
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