Characterization of female germline stem cells from adult mouse ovaries and the role of rapamycin on them
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.
KeywordsFemale germline stem cells Characterization Rapamycin Mouse
This study was supported by Basal Research Fund of Northwest A&F University (2452015034) and Agricultural Science and Technology Innovation and Key Project of Shaanxi Province (2016NY-094).
- Bland ML, Desclozeaux M, Ingraham HA (2003) Tissue growth and remodeling of the embryonic and adult adrenal gland. Ann N Y Acad Sci 995:59–72. https://doi.org/10.1111/j.1749-6632.2003.tb03210.x CrossRefGoogle Scholar
- Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA (2009) Rapamycin fed late in life extends lifespan in genetically heterogenous mice. Nature 460:392–395. https://doi.org/10.1038/nature08221 CrossRefGoogle Scholar
- Mitchell RT, Saunders PT, Childs AJ, Cassidy-Kojima C, Anderson RA, Wallace WH, Kelnar CJ, Sharpe RM (2010) Xenografting of human fetal testis tissue: a new approach to study fetal testis development and germ cell differentiation. Hum Reprod 25:2405–2414. https://doi.org/10.1093/humrep/deq183 CrossRefGoogle Scholar
- Pennetier S, Uzbekova S, Perreau C, Papillier P, Mermillod P, Dalbiès-Tran R (2004) Spatio-temporal expression of the germ cell marker genes MATER, ZAR1, GDF9, BMP15, and VASA in adult bovine tissues, oocytes, and preimplantation embryos. Biol Reprod 71:1359–1366. https://doi.org/10.1095/biolreprod.104.030288 CrossRefGoogle Scholar
- Zhang XL, Wu J, Wang J, Shen T, Li H, Lu J, Gu Y, Kang Y, Wong CH, Ngan CY, Shao Z, Wu J, Zhao X (2016) Integrative epigenomic analysis reveals unique epigenetic signatures involved in unipotency of mouse female germline stem cells. Genome Biol 17:162. https://doi.org/10.1186/s13059-016-1023-z CrossRefGoogle Scholar