Life-long in vivo cell-lineage tracing shows that no oogenesis originates from putative germline stem cells in adult mice

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 50; pp. 17983 - 17988
• Main Authors: Zhang, Hua, Liu, Lian, Li, Xin, Busayavalasa, Kiran, Shen, Yan, Hovatta, Outi, Gustafsson, Jan-Åke, Liu, Kui
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 16.12.2014; National Acad Sciences
• Subjects: adult; Adult stem cells; Adult Stem Cells - cytology; adults; Analysis of Variance; animal cell; animal experiment; animal ovaries; animal tissue; Animals; Animals, Genetically Modified; Bacteria; Biological Sciences; Cancer and Oncology; Cancer och onkologi; Cell and Molecular Biology; cell lineage; Cell Lineage - physiology; Cell lines; Cell- och molekylärbiologi; controlled study; corpus luteum; cre recombinase; Crosses, Genetic; Female; Follicle tracing; Follicles; gene expression; Gene Expression Profiling; Genes; genetically engineered mouse strain; Genetically modified mouse models; Germ cells; germline stem cell; growth differentiation factor 9; Histological Techniques; Life span; Life-long observations; lifespan; male; messenger RNA; Mice; Mice, Mutant Strains; mouse; Mus; No postnatal oocyte regeneration; nonhuman; oocyte development; Oocyte tracing; Oocytes; Oocytes - physiology; Oogenesis; Oogenesis - physiology; Ovaries; ovary; primordial germ cell; regeneration; Reproduction; reverse transcription polymerase chain reaction; Rodents; somatic cell; Somatic cells; spermatogenesis; Stem cells; Tamoxifen; oocyte tracing; no postnatal oocyte regeneration; genetically modified mouse models; follicle tracing; life-long observations
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1421047111

Whether or not oocyte regeneration occurs in adult life has been the subject of much debate. In this study, we have traced germ-cell lineages over the life spans of three genetically modified mouse models and provide direct evidence that oogenesis does not originate from any germline stem cells (GSCs) in adult mice. By selective ablation of all existing oocytes in a Gdf9-Cre;iDTR mouse model, we have demonstrated that no new germ cells were ever regenerated under pathological conditions. By in vivo tracing of oocytes and follicles in the Sohlh1-CreER ᵀ²;R26R and Foxl2-CreER ᵀ²;mT/mG mouse models, respectively, we have shown that the initial pool of oocytes is the only source of germ cells throughout the life span of the mice and that no adult oogenesis ever occurs under physiological conditions. Our findings clearly show that there are no GSCs that contribute to adult oogenesis in mice and that the initial pool of oocytes formed in early life is the only source of germ cells throughout the entire reproductive life span. Significance Whether or not oocyte regeneration occurs in the adult mammalian ovary has been the subject of much debate. By performing a series of in vivo cell-lineage tracing experiments, we have supplied compelling in vivo evidence that mammalian oocytes are not regenerated from any putative germline stem cells in adult life. Our current study provides conclusive evidence that the initial oocyte pool is the only source of fertility throughout reproductive life in mammals.