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成年小鼠卵巢雌性生殖系干细胞的特性及雷帕霉素对其的作用

Characterization of female germline stem cells from adult mouse ovaries and the role of rapamycin on them.

作者信息

Yang Hong, Yao Xi, Tang Furong, Wei Yudong, Hua Jinlian, Peng Sha

机构信息

College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, No. 22 Xinong Rd., Xianyang SN910, Yangling, 712100, Shaanxi, China.

出版信息

Cytotechnology. 2018 Apr;70(2):843-854. doi: 10.1007/s10616-018-0196-6. Epub 2018 Jan 25.

Abstract

Germline stem cells (GSCs) play an indispensable role in establishing the fertility of an organism. The isolation and culture of adult female GSCs (FGSCs) have provided a robust foundation to study the development of female germ cells in rodents. However, many problems still need to be identified, such as the origin and location of FGSCs and the specific markers for screening. In this study, we acquired FGSCs that stably expressed Oct4 from Oct4 promoter-GFP transgenic mouse ovarian surface epithelium and cortical layer, and identified the cells possessing the representative features including the expression of GSCs marker genes and the potentiality of differentiation into all three germ layers in vitro. Moreover, rapamycin was confirmed to promote proliferation of mouse FGSCs and inhibit the differentiation capability in vivo. In addition to the reported disinfection function, rapamycin inhibited the activation of primordial follicles, as the inhibitor of mechanistic target of rapamycin pathway. These results will contribute to the study on folliculogenesis or oogenesis mechanism and have important implications on developing new technology and therapeutic approach in medicine for premature ovarian failure, infertility and even ovary remodelling in future.

摘要

生殖系干细胞(GSCs)在建立生物体的生育能力方面发挥着不可或缺的作用。成年雌性生殖系干细胞(FGSCs)的分离和培养为研究啮齿动物雌性生殖细胞的发育提供了坚实的基础。然而,仍有许多问题有待明确,例如FGSCs的起源和位置以及用于筛选的特异性标志物。在本研究中,我们从Oct4启动子-GFP转基因小鼠的卵巢表面上皮和皮质层中获取了稳定表达Oct4的FGSCs,并鉴定出具有代表性特征的细胞,包括生殖系干细胞标记基因的表达以及在体外分化为所有三个胚层的潜能。此外,雷帕霉素被证实可促进小鼠FGSCs的增殖并在体内抑制其分化能力。除了已报道的消毒功能外,雷帕霉素作为雷帕霉素作用靶点途径的抑制剂,还可抑制原始卵泡的激活。这些结果将有助于卵泡发生或卵子发生机制的研究,并对未来开发针对卵巢早衰、不孕症甚至卵巢重塑的医学新技术和治疗方法具有重要意义。

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