The Rise and Fall of Oogonial Stem Cells Within the Historical Context of Adult Stem Cells

  • Shweta Nayak
  • Yu Ren
  • Aleksandar RajkovicEmail author


For decades, it has been believed that adult human female reproductive potential was determined by a finite number of primordial follicles, which are established in the embryonic gonad. The rise of adult stem cells in other organs inevitably led to investigations that searched for stem cells in various organs of the reproductive tract, including ovaries, endometrium, and uterus. Within ovaries, somatic stem cells that drive granulosa cell proliferation and provide an essential support environment for differentiating oocytes have been characterized with little controversy. No adult stem cell claim has stirred as much controversy as the one that oogonial stem cells exist and can give rise to neo-oogenesis. Such a finding would render women, previously believed to have a nonrenewable gamete supply, remarkably more like men, who are able to replenish their germ cells. We review the rise and fall of oogonial stem cells in the historical context of the general concept of adult stem cells.


Ovary Stem cell Biology Oocyte Ovarian reserve 


  1. 1.
    Ramalho-Santos M, Willenbring H. On the origin of the term “stem cell”. Cell Stem Cell. 2007;1:35–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Richards RJ. The tragic sense of life: Ernst Haeckel and the struggle over evolutionary thought. Chicago: University of Chicago Press; 2008.CrossRefGoogle Scholar
  3. 3.
    Haeckel E. Natürliche Schöpfungsgeschichte. Berlin: Georg Reimer; 1868. 15th lecture.Google Scholar
  4. 4.
    Haeckel E. Anthropogenie oder Entwickelungsgeschichte des Menschen. 3rd ed. Leipzig: Wilhelm Engelmann; 1877. p. 144. my translation.Google Scholar
  5. 5.
    Boveri T. Zur Frage der Entstehung maligner Tumoren. Jena: Gustav Fischer; 1914. p. 2.Google Scholar
  6. 6.
    Weismann A. Die Continuität des Keimplasma’s als Grundlage einer Theorie der Vererbung. Jena: Gustav Fischer; 1885. p. 5–21.Google Scholar
  7. 7.
    Satzinger H. Differenz und Vererbung. Geschlechterordnungen in der Genetik und Hormonforschung 1890–1950. Cologne: Böhlau Verlag; 2009. p. 85–97.Google Scholar
  8. 8.
    Baltzer F. Theodor Boveri: life and work of a great biologist 1862–1915. Berkeley, CA: University of California Press; 1967.Google Scholar
  9. 9.
    Harwood J. Styles of scientific thought. The German genetics community 1900-1933. Chicago: University of Chicago Press; 1993. p. 52–5.Google Scholar
  10. 10.
    Haecker V. Über Gedächtnis, Vererbung und Pluripotenz. Jena: Gustav Fischer; 1914. p. 63–85.Google Scholar
  11. 11.
    Haecker R. Das Leben von Valentin Haecker. Zoologischer Anzeiger. 1965;174:1–22.Google Scholar
  12. 12.
    Pappenheim A. Zwei Fälle akuter grosslymphozytärer Leukämie. Folia Haematologica. 1907;4:301–8. On Pappenheim and his haematological work see: Dinser, Ricarda. Der Beitrag Artur Pappenheims zur Hämatologie um die Jahrhundertwende. Ruhr-Universität Bochum.Google Scholar
  13. 13.
    Dantschakoff W. Untersuchungen über die Entwickelung des Blutes und Bindegewebes bei den Vögeln. Anatomische Hefte. 1908;37:471–589. On Dantschakoff’s international career see Satzinger, op. cit. (note 19), p. 231–2, 394–6.CrossRefGoogle Scholar
  14. 14.
    Maximow A. Der Lymphozyt als gemeinsame Stammzelle der verschiedenen Blutelemente in der embryonalen Entwicklung und im postfetalen Leben der Säugetiere. Folia Haematologica. 1909;8:125–34. Konstantinov IE. In search of Alexander A. Maximow: the man behin.Google Scholar
  15. 15.
    Neumann E. Hämatologische Studien I.–III. Virchows Archiv für pathologische Anatomie. 225-77 (1896); 174, 41–78 (1903); 207, 379–412 (1912).Google Scholar
  16. 16.
    Ehrlich P, Lazarus A. Histology of the blood: normal and pathological. Cambridge: University Press; 1900. p. 81.Google Scholar
  17. 17.
    Neumann E. Ueber die Bedeutung des Knochenmarkes für die Blutbildung, Vorläufige Mittheilung. Centralblatt für die medicinischen Wissenschaften. 1868; 6(44). Neumann-Redlin v Meding, E. Der Pathologe Ernst Neumann (1834–1918) und sein Beitrag zur Begründung.Google Scholar
  18. 18.
    Monti M, Perotti C, Del Fante C, Cervio M, Redi CA. Stem cells: sources and therapies. BiolRes [Internet]. 2012; 45(3):207–14. Available from:
  19. 19.
    Cairns J. Mutation selection and the natural history of cancer. Nature. 1975;255:197–200.CrossRefPubMedGoogle Scholar
  20. 20.
    Cairns J. Somatic stem cells and the kinetics of mutagenesis and carcinogenesis. Proc Natl Acad Sci U S A. 2002;99:10567–70.PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Cairns J. Cancer and the immortal strand hypothesis. Genetics. 2006;174:1069–72.PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Schofield R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells. 1978;4:7–25.PubMedGoogle Scholar
  23. 23.
    Scheres B. Stem-cell niches: nursery rhymes across kingdoms. Nat Rev Mol Cell Biol [Internet]. 2007 [cited 2014 May 26]; 8(5):345–54. Available from:
  24. 24.
    Jones DL, Wagers AJ. No place like home: anatomy and function of the stem cell niche. Nat Rev Mol Cell Biol [Internet]. 2008 [cited 2014 May 26]; 9(1):11–21. Available from:
  25. 25.
    Knoblich JA. Mechanisms of asymmetric stem cell division. Cell [Internet]. 2008 [cited 2014 May 26]; 132(4):583–97. Available from:
  26. 26.
    Morrison SJ, Spradling AC. Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell [Internet]. 2008 [cited 2014 May 26]; 132(4):598–611. Available from:
  27. 27.
    Kimble JE, White JG. On the control of germ cell development in Caenorhabditis elegans. Dev Biol [Internet]. 1981; 81(2):208–19. Available from:
  28. 28.
    Kiger AA, Jones DL, Schulz C, Rogers MB, Fuller MT. Stem cell self-renewal specified by JAK-STAT activation in response to a support cell cue. Science [Internet]. 2001 [cited 2014 May 26]; 294(5551):2542–5. Available from:
  29. 29.
    Tulina N, Matunis E. Control of stem cell self-renewal in Drosophila spermatogenesis by JAK-STAT signaling. Science [Internet]. 2001 [cited 2014 May 26]; 294(5551):2546–9. Available from:
  30. 30.
    Fuller MT, Spradling AC. Male and female Drosophila germline stem cells: two versions of immortality. Science [Internet]. 2007 [cited 2014 May 26]; 316(5823):402–4. Available from:
  31. 31.
    Nagy A, Rossant J, Nagy R, Abramow-Newerly W, Roder JC. Derivation of completely cell culture-derived mice from early-passage embryonic stem cells. Proc Natl Acad Sci U S A [Internet]. 1993; 90(18):8424–8. Available from:
  32. 32.
    Pera MF, Reubinoff B, Trounson A. Human embryonic stem cells. J Cell Sci. 2000;113:5–10.PubMedGoogle Scholar
  33. 33.
    Donovan PJ, de Miguel MP. Turning germ cells into stem cells. Curr Opin Genet Dev [Internet]. 2003 [cited 2014 Jul 20]; 13(5):463–71. Available from:
  34. 34.
    Thomson JA. Embryonic stem cell lines derived from human blastocysts. Science (80-) [Internet]. 1998 [cited 2014 May 23]; 282(5391):1145–7. Available from:
  35. 35.
    Spradling A, Fuller MT, Braun RE, Yoshida S. Germline stem cells. Cold Spring Harb Perspect Biol [Internet]. 2011 [cited 2014 Jul 9]; 3(11):a002642. Available from:
  36. 36.
    Cinquin O. Purpose and regulation of stem cells: a systems-biology view from the Caenorhabditis elegans germ line. J Pathol. 2009;217:186–98.PubMedCentralCrossRefPubMedGoogle Scholar
  37. 37.
    Crittenden SL, Leonhard KA, Byrd DT, Kimble J. Cellular analyses of the mitotic region in the Caenorhabditis elegans adult germ line. Mol Biol Cell. 2006;17(July):3051–61.PubMedCentralCrossRefPubMedGoogle Scholar
  38. 38.
    Cinquin O, Crittenden SL, Morgan DE, Kimble J. Progression from a stem cell-like state to early differentiation in the C. elegans germ line. Proc Natl Acad Sci U S A [Internet]. 2010 [cited 2014 Jul 16]; 107(5):2048–53. Available from:
  39. 39.
    Wong MD, Jin Z, Xie T. Germline, molecular mechanisms of regulation, stem cell. Annu Rev Genet. 2005;39:173–95.CrossRefPubMedGoogle Scholar
  40. 40.
    Spradling AC. Developmental genetics of oogenesis. In: Bate M, Martinez Arias A, editors. The development of Drosophila melanogaster. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 1993.Google Scholar
  41. 41.
    De Felici M, Barrios F. Seeking the origin of female germline stem cells in the mammalian ovary. Reproduction [Internet]. 2013 [cited 2014 Jul 19]; 146(4):R125–30. Available from:
  42. 42.
    Böttger SA, Walker CW, Unuma T. Care and maintenance of adult echinoderms. Methods Cell Biol. 2004;74:17–38.CrossRefPubMedGoogle Scholar
  43. 43.
    Kurimoto K, Yabuta Y, Ohinata Y, Shigeta M, Yamanaka K, Saitou M. Complex genome-wide transcription dynamics orchestrated by Blimp1 for the specification of the germ cell lineage in mice. Genes Dev [Internet]. 2008 [cited 2014 Jul 15]; 22(12):1617–35. Available from:
  44. 44.
    Yamaji M, Seki Y, Kurimoto K, Yabuta Y, Yuasa M, Shigeta M, et al. Critical function of Prdm14 for the establishment of the germ cell lineage in mice. Nat Genet [Internet]. 2008 [cited 2014 Jul 15]; 40(8):1016–22. Available from:
  45. 45.
    Zuckerman S. The number of oocytes in the mature ovary. Recent Prog Horm Res. 1951;6:63–108.Google Scholar
  46. 46.
    Baker TG. A quantitative and cytological study of germ cells in human ovaries. Proc R Soc Lond B Biol Sci. 1963;158:417–33.CrossRefPubMedGoogle Scholar
  47. 47.
    Reynaud K, Cortvrindt R, Verlinde F, De Schepper J, Bourgain C, Smitz J. Number of ovarian follicles in human fetuses with the 45,X karyotype. Fertil Steril. 2004;81:1112–9.CrossRefPubMedGoogle Scholar
  48. 48.
    Kurilo LF. Oogenesis in antenatal development in man. Hum Genet. 1981;57:86–92.CrossRefPubMedGoogle Scholar
  49. 49.
    Johnson J, Bagley J, Skaznik-Wikiel M, Lee H-J, Adams GB, Niikura Y, et al. Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell [Internet]. 2005 29 [cited 2014 Jul 20]; 122(2):303–15. Available from:
  50. 50.
    Mork L, Tang H, Batchvarov I, Capel B. Mouse germ cell clusters form by aggregation as well as clonal divisions. Mech Dev. 2012;128:591–6.PubMedCentralCrossRefPubMedGoogle Scholar
  51. 51.
    Pepling ME, Spradling AC. Mouse ovarian germ cell cysts undergo programmed breakdown to form primordial follicles. Dev Biol [Internet]. 2001 [cited 2014 Jul 16]; 234(2):339–51. Available from:
  52. 52.
    Lechowska A, Bilinski S, Choi Y, Shin Y, Kloc M, Rajkovic A. Premature ovarian failure in nobox-deficient mice is caused by defects in somatic cell invasion and germ cell cyst breakdown. J Assist Reprod Genet. 2011;28:583–9.PubMedCentralCrossRefPubMedGoogle Scholar
  53. 53.
    Pangas SA, Rajkovic A. Follicular development: mouse, sheep, and human models [Internet]. In: Plant TM, Zeleznik AJ, editors. Knobil and Neill’s physiology of reproduction. Elsevier Inc., Amsterdam. Available from:
  54. 54.
    Sullivan SD, Castrillon DH. Insights into primary ovarian insufficiency through genetically engineered mouse models. Semin Reprod Med. 2011;29(4):283–98.CrossRefPubMedGoogle Scholar
  55. 55.
    Driancourt MA, Reynaud K, Cortvrindt R, Smitz J. Roles of KIT and KIT LIGAND in ovarian function. Rev Reprod. 2000;5:143–52.CrossRefPubMedGoogle Scholar
  56. 56.
    Nilsson EE, Skinner MK. Bone morphogenetic protein-4 acts as an ovarian follicle survival factor and promotes primordial follicle development. Biol Reprod. 2003;69:1265–72.CrossRefPubMedGoogle Scholar
  57. 57.
    Parrott JA, Skinner MK. NoKit-ligand/stem cell factor induces primordial follicle development and initiates folliculogenesis. Endocrinology. 1999;140:4262–71.PubMedGoogle Scholar
  58. 58.
    Nilsson E, Parrott JA, Skinner MK. Basic fibroblast growth factor induces primordial follicle development and initiates folliculogenesis. Mol Cell Endocrinol. 2001;175:123–30.CrossRefPubMedGoogle Scholar
  59. 59.
    Nilsson EE, Kezele P, Skinner MK. Leukemia inhibitory factor (LIF) promotes the primordial to primary follicle transition in rat ovaries. Mol Cell Endocrinol. 2002;188:65–73.CrossRefPubMedGoogle Scholar
  60. 60.
    John GB, Gallardo TD, Shirley LJ, Castrillon DH. Foxo3 is a PI3K dependent molecular switch controlling the initiation of oocyte growth. Dev Biol. 2008;321:197–204.PubMedCentralCrossRefPubMedGoogle Scholar
  61. 61.
    Castrillon DH, Miao L, Kollipara R, Horner JW, DePinho RA. Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a. Science. 2003;301:215–8.CrossRefPubMedGoogle Scholar
  62. 62.
    Gallardo TD, John GB, Bradshaw K, et al. Sequence variation at the human FOXO3 locus: a study of premature ovarian failure and primary amenorrhea. Hum Reprod. 2008;23:216–21.PubMedCentralCrossRefPubMedGoogle Scholar
  63. 63.
    Dunlop CE, Telfer EE, Anderson RA. Ovarian stem cells--potential roles in infertility treatment and fertility preservation. Maturitas [Internet]. Elsevier Ireland Ltd; 2013 [cited 2014 Apr 28]; 76(3):279–83. Available from:
  64. 64.
    Reddy P, Liu L, Adhikari D, Jagarlamudi K, Rajareddy S, Shen Y, et al. Oocyte-specific deletion of Pten causes premature activation of the primordial follicle pool. Science. 2008;319(February):611–3.CrossRefPubMedGoogle Scholar
  65. 65.
    Adhikari D, Zheng W, Shen Y, Gorre N, Hämäläinen T, Cooney AJ, et al. Tsc/mTORC1 signaling in oocytes governs the quiescence and activation of primordial follicles. Hum Mol Genet. 2009;19(3):397–410.PubMedCentralCrossRefPubMedGoogle Scholar
  66. 66.
    Li J, Kawamura K, Cheng Y, et al. Activation of dormant ovarian follicles to generate mature eggs. Proc Natl Acad Sci U S A. 2010;107:10280–4.PubMedCentralCrossRefPubMedGoogle Scholar
  67. 67.
    Kawamura K, Cheng Y, Suzuki N, Deguchi M, Sato Y, Takae S, et al. Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. Proc Natl Acad Sci U S A [Internet]. 2013;110(43):17474–9. Available from: Scholar
  68. 68.
    Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, Matzuk M. Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature. 1996;383(6600):531–5.CrossRefPubMedGoogle Scholar
  69. 69.
    Dierich A, Sairam MR, Monaco L, Fimia GM, Gansmuller A, LeMeur M, et al. Impairing follicle-stimulating hormone (FSH) signaling in vivo: targeted disruption of the FSH receptor leads to aberrant gametogenesis and hormonal imbalance. Proc Natl Acad Sci U S A. 1998;95(22):13612–7.PubMedCentralCrossRefPubMedGoogle Scholar
  70. 70.
    Baker J, Hardy MP, Zhou J, Bondy C, Lupu F, Bellvé AR, Efstratiadis A. Effects of an Igf1 gene null mutation on mouse reproduction. Mol Endocrinol. 1996;10(7):903–18.PubMedGoogle Scholar
  71. 71.
    Matzuk MM, Finegold MJ, Su JG, Hsueh AJ, Bradley A. Alpha-inhibin is a tumour-suppressor gene with gonadal specificity in mice. Nature. 1992;360:313–9.CrossRefPubMedGoogle Scholar
  72. 72.
    Sicinski P, Donaher JL, Geng Y, Parker SB, Gardner H, Park MY, et al. Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis. Nature. 1996;384:470–4.CrossRefPubMedGoogle Scholar
  73. 73.
    Tomic D, Miller KP, Kenny HA, Woodruff TK, Hoyer P, Flaws JA. Ovarian follicle development requires Smad3. Mol Endocrinol. 2004;18(February):2224–40.CrossRefPubMedGoogle Scholar
  74. 74.
    Freiman RN, Albright SR, Zheng S, Sha WC, Hammer RE, Tjian R. Requirement of tissue-selective TBP-associated factor TAFII105 in ovarian development. Science. 2001;293:2084–7.CrossRefPubMedGoogle Scholar
  75. 75.
    Kumar TR, Wang Y, Lu N, Matzuk MM. Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nat Genet. 1997;15(2):201–4.CrossRefPubMedGoogle Scholar
  76. 76.
    Lubahn DB, Moyer JS, Golding TS, Couse JF, Korach KS, Smithies O. Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc Natl Acad Sci U S A. 1993;90(December):11162–6.PubMedCentralCrossRefPubMedGoogle Scholar
  77. 77.
    Krege JH, Hodgin JB, Couse JF, Enmark E, Warner M, Mahler JF, et al. Generation and reproductive phenotypes of mice lacking estrogen receptor beta. Proc Natl Acad Sci U S A. 1998;95(December):15677–82.PubMedCentralCrossRefPubMedGoogle Scholar
  78. 78.
    Simon AM, Goodenough DA, Li E, Paul DL. Female infertility in mice lacking connexin 37. Nature. 1997;385:525–9.CrossRefPubMedGoogle Scholar
  79. 79.
    Matzuk MM, Kumar TR, Bradley A. Different phenotypes for mice deficient in either activins or activin receptor type II. Nature. 1995;374:356–60.CrossRefPubMedGoogle Scholar
  80. 80.
    Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature [Internet]. 2004;428(6979):145–50. Available from: Scholar
  81. 81.
    Fujiwara Y, Komiya T, Kawabata H, Sato M, Fujimoto H, Furusawa M, et al. Isolation of a DEAD-family protein gene that encodes a murine homolog of Drosophila vasa and its specific expression in germ cell lineage. Proc Natl Acad Sci U S A [Internet]. 1994;91(25):12258–62. Available from: Scholar
  82. 82.
    Noce T, Okamoto-Ito S, Tsunekawa N. Vasa homolog genes in mammalian germ cell development. Cell Struct Funct [Internet]. 2001;26(3):131–6. Available from: Scholar
  83. 83.
    Johnson J, Skaznik-wikiel M, Lee H, Tilly JC, Tilly JL. Setting the record straight on data supporting postnatal oogenesis in female mammals. Cell Cycle. 2005;4(November):1471–7.PubMedGoogle Scholar
  84. 84.
    Telfer EE, Gosden RG, Byskov AG, Spears N, Albertini D, Andersen CY, et al. On regenerating the ovary and generating controversy. Cell [Internet]. 2005 [cited 2014 Jul 21]; 122(6):821–2. Available from:
  85. 85.
    Bristol-Gould SK, Kreeger PK, Selkirk CG, Kilen SM, Mayo KE, Shea LD, et al. Fate of the initial follicle pool: empirical and mathematical evidence supporting its sufficiency for adult fertility. Dev Biol [Internet]. 2006 [cited 2014 Jul 21]; 298(1):149–54. Available from:
  86. 86.
    Krarup T. Effect of 9,10-dimethyl-1,2-benzanthracene on the mouse ovary. Ovarian tumorigenesis. Br J Cancer. 1970;24(1):168–86.PubMedCentralCrossRefPubMedGoogle Scholar
  87. 87.
    Krarup T. Oocyte survival in the mouse ovary after treatment with 9,10-dimethyl-1,2-benzanthracene. J Endocrinol. 1970;46(4):483–95.CrossRefPubMedGoogle Scholar
  88. 88.
    Motta PM, Makabe S. Germ cells in the ovarian surface during fetal development in humans. A three-dimensional microanatomical study by scanning and transmission electron microscopy. J Submicrosc Cytol. 1986;18(2):271–90.PubMedGoogle Scholar
  89. 89.
    Motta PM, Makabe S. Elimination of germ cells during differentiation of the human ovary: an electron microscopic study. Eur J Obstet Gynecol Reprod Biol. 1986;22(5–6):271–86.CrossRefPubMedGoogle Scholar
  90. 90.
    Eppig JJ, Wigglesworth K. Development of mouse and rat oocytes in chimeric reaggregated ovaries after interspecific exchange of somatic and germ cell components. Biol Reprod [Internet]. 2000;63(4):1014–23. Available from: Scholar
  91. 91.
    Carroll J, Whittingham DG, Wood MJ, Telfer E, Gosden RG. Extra-ovarian production of mature viable mouse oocytes from frozen primary follicles. J Reprod Fertil. 1990;90(1):321–7.CrossRefPubMedGoogle Scholar
  92. 92.
    Ballas CB, Zielske SP, Gerson SL. Adult bone marrow stem cells for cell and gene therapies: implications for greater use. J Cell Biochem Suppl. 2002;38:20–8.CrossRefPubMedGoogle Scholar
  93. 93.
    Jadczyk T, Pedziwiatr D, Wojakowski W. New advances in stem cell research: practical implications for regenerative medicine. Polish Arch Intern Med. 2014;124:417–26.Google Scholar
  94. 94.
    Lawson KA, Hage WJ. Clonal analysis of the origin of primordial germ cells in the mouse. Ciba Found Symp. 1994;182:68–84.PubMedGoogle Scholar
  95. 95.
    Edelmann W, Keeney S, Jasin M, Di Giacomo M, Barchi M. Distinct DNA-damage-dependent and -independent responses drive the loss of oocytes in recombination-defective mouse mutants. Proc Natl Acad Sci U S A. 2005;102(3):737–42.PubMedCentralCrossRefPubMedGoogle Scholar
  96. 96.
    Hematti P, Sloand EM, Carvallo CA, Albert MR, Yee CL, Fuehrer MM, et al. Absence of donor-derived keratinocyte stem cells in skin tissues cultured from patients after mobilized peripheral blood hematopoietic stem cell transplantation. Exp Hematol [Internet]. 2002;30(8):943–9. Available from: Scholar
  97. 97.
    Ainsworth C. Bone cells linked to creation of fresh eggs in mammals. Nature [Internet]. 2005;436(7051):609. Available from: Scholar
  98. 98.
    Skeptics demand duplication of controversial fertility claim. Maine company falls a-fowl for smuggling bird flu. As the virulent bird flu sweeping through Asia. 2005;11(9):2005.Google Scholar
  99. 99.
    Eggan K, Jurga S, Gosden R, Min IM, Wagers AJ. Ovulated oocytes in adult mice derive from non-circulating germ cells. Nature. 2006;441(June):1109–14.CrossRefPubMedGoogle Scholar
  100. 100.
    Zou K, Yuan Z, Yang Z, Luo H, Sun K, Zhou L, et al. Production of offspring from a germline stem cell line derived from neonatal ovaries. Nat Cell Biol [Internet]. 2009 [cited 2014 Jul 21]; 11(5):631–6. Available from:
  101. 101.
    Toyooka Y, Tsunekawa N, Takahashi Y, Matsui Y, Satoh M, Noce T. Expression and intracellular localization of mouse Vasa-homologue protein during germ cell development. Mech Dev. 2000;93(1–2):139–49.CrossRefPubMedGoogle Scholar
  102. 102.
    Castrillon DH, Quade BJ, Wang TY, Quigley C, Crum CP. The human VASA gene is specifically expressed in the germ cell lineage. Proc Natl Acad Sci U S A. 2000;97:9585–90.PubMedCentralCrossRefPubMedGoogle Scholar
  103. 103.
    Pacchiarotti J, Maki C, Ramos T, Marh J, Howerton K, Wong J, et al. Differentiation potential of germ line stem cells derived from the postnatal mouse ovary. Differentiation [Internet]. Elsevier; 2010 [cited 2014 Jul 10]; 79(3):159–70. Available from:
  104. 104.
    Zhang H, Zheng W, Shen Y, Adhikari D, Ueno H, Liu K. Experimental evidence showing that no mitotically active female germline progenitors exist in postnatal mouse ovaries. Proc Natl Acad Sci U S A [Internet]. 2012 [cited 2014 May 26]; 109(31):12580–5. Available from:
  105. 105.
    Red-Horse K, Ueno H, Weissman IL, Krasnow MA. Coronary arteries form by developmental reprogramming of venous cells. Nature [Internet]. Nature Publishing Group; 2010 [cited 2014 Jul 11]; 464(7288):549–53. Available from:
  106. 106.
    Rinkevich Y, Lindau P, Ueno H, Longaker MT, Weissman IL. Germ-layer and lineage-restricted stem/progenitors regenerate the mouse digit tip. Nature [Internet]. Nature Publishing Group; 2011 [cited 2014 Jul 17]; 476(7361):409–13. Available from:
  107. 107.
    Lei L, Spradling AC. Female mice lack adult germ-line stem cells but sustain oogenesis using stable primordial follicles. Proc Natl Acad Sci U S A [Internet]. 2013 [cited 2014 May 26]; 110(21):8585–90. Available from:
  108. 108.
    Hayashi S, McMahon AP. Efficient recombination in diverse tissues by a tamoxifen-inducible form of Cre: a tool for temporally regulated gene activation/inactivation in the mouse. Dev Biol [Internet]. 2002 [cited 2014 Jul 11]; 244(2):305–18. Available from:
  109. 109.
    Srinivas S, Watanabe T, Lin CS, William CM, Tanabe Y, Jessell TM, et al. Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus. BMC Dev Biol [Internet]. 2001;1:4. Available from: Scholar
  110. 110.
    Ng A, Tan S, Singh G, Rizk P, Swathi Y, Tan TZ, et al. Lgr5 marks stem/progenitor cells in ovary and tubal epithelia. Nat Cell Biol [Internet]. 2014 [cited 2014 Dec 5]; 16(8):745–57. Available from:
  111. 111.
    Zheng W, Zhang H, Gorre N, Risal S, Shen Y, Liu K. Two classes of ovarian primordial follicles exhibit distinct developmental dynamics and physiological functions. Hum Mol Genet [Internet]. 2014 [cited 2014 Dec 10]; 23(4):920–8. Available from:
  112. 112.
    Capel B. Ovarian epithelium regeneration by Lgr5(+) cells. Nat Cell Biol [Internet]. Nature Publishing Group; 2014 [cited 2014 Dec 10]; 16(8):743–4. Available from:
  113. 113.
    Mork L, Maatouk DM, McMahon JA, Guo JJ, Zhang P, McMahon AP, et al. Temporal differences in granulosa cell specification in the ovary reflect distinct follicle fates in mice. Biol Reprod [Internet]. 2012 [cited 2014 Dec 8]; 86(2):37. Available from:
  114. 114.
    Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell [Internet]. 2007 [cited 2014 Jul 9]; 131(5):861–72. Available from:
  115. 115.
    Sun N, Zhao H. Seamless correction of the sickle cell disease mutation of the HBB gene in human induced pluripotent stem cells using TALENs. Biotechnol Bioeng. 2014;111(5):1048–53.CrossRefPubMedGoogle Scholar
  116. 116.
    Sebastiano V, Maeder ML, Angstman JF, Haddad B, Khayter C, Yeo DT, et al. In situ genetic correction of the sickle cell anemia mutation in human induced pluripotent stem cells using engineered zinc finger nucleases. Stem Cells. 2011;29:1717–26.PubMedCentralCrossRefPubMedGoogle Scholar
  117. 117.
    Hayashi K, Saitou M. Generation of eggs from mouse embryonic stem cells and induced pluripotent stem cells. Nat Protoc [Internet]. Nature Publishing Group; 2013; 8(8):1513–24. Available from:

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of Obstetrics, Gynecology, and Reproductive SciencesMagee-Womens Research Institute, University of PittsburghPittsburghUSA

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