Human GV oocytes generated by mitotically active germ cells obtained from follicular aspirates.
Human GV oocytes generated by mitotically active germ cells obtained from follicular aspirates.
复制标题
由从卵泡抽吸物中获得的有丝分裂活性生殖细胞产生的人 GV 卵母细胞
DOI：
10.1038/srep28218
复制
发表时间：
2016-06-30
影响因子：
4.6
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Ding X;Liu G;Xu B;Wu C;Hui N;Ni X;Wang J;Du M;Teng X;Wu J
人类女性生殖系干细胞（FGSC）为理解人类卵子发生、延迟绝经、治疗不孕症和提供保持生育能力的新策略开辟了新的机会。然而，成人卵巢组织的短缺阻碍了其未来的研究和临床应用。在这里，我们已经建立了FGSC线从稀缺的卵巢皮质组织存在于卵泡吸出物（faFGSC），这是生产和丢弃在世界各地的体外受精中心。faFGSC具有涉及基因表达谱的生殖系干细胞的特征、生长特征和与从手术从患者移除的卵巢皮质获得的FGSC（srFGSC）一致的正常核型。此外，faFGSC具有发育潜力，包括在无饲养层条件下自发分化为卵母细胞，通过间隙连接和旁分泌因子与颗粒细胞沟通，在RA诱导后进入减数分裂，以及在注射到异种移植到成年免疫缺陷雌性小鼠中的人卵巢皮质组织中后形成卵泡。最后，我们建立了一套指导FGSCs体外分化为GV期卵母细胞的策略，并揭示了其发育机制。我们的研究不仅为获得用于医学治疗的人FGSCs提供了一种新的方法，而且为研究人类体外卵子发生开辟了几条途径。
Human female germline stem cells (FGSCs) have opened new opportunities for understanding human oogenesis, delaying menopause, treating infertility, and providing a new strategy for preserving fertility. However, the shortage of adult human ovaries tissues available impedes their future investigations and clinical applications. Here, we have established FGSC lines from scarce ovarian cortical tissues that exist in follicular aspirates (faFGSCs), which are produced and discarded in in vitro fertilization centers worldwide. The faFGSCs have characteristics of germline stem cells involved in the gene expression profile, growth characteristics, and a normal karyotype consistent with that of FGSCs obtained from ovarian cortexes surgically removed from patients (srFGSCs). Furthermore, faFGSCs have developmental potentials including spontaneous differentiation into oocytes under feeder-free conditions, communicating with granulosa cells by gap junctions and paracrine factors, entering meiosis after RA induction, as well as forming follicles after injection into human ovarian cortical tissues xenografted into adult immunodeficient female mice. Lastly, we developed a strategy guiding FGSCs differentiated into germinal vesicle (GV) stage oocytes in vitro and revealed their developmental mechanisms. Our study not only provides a new approach to obtain human FGSCs for medical treatment, but also opens several avenues to investigate human oogenesis in vitro.