About this Journal Submit a Manuscript Table of Contents
BioMed Research International
Volume 2013 (2013), Article ID 682326, 10 pages
http://dx.doi.org/10.1155/2013/682326
Review Article

Very Small Embryonic-Like Stem Cells: Implications in Reproductive Biology

Stem Cell Biology Department, National Institute for Research in Reproductive Health (ICMR), Mumbai, Maharashtra 400 012, India

Received 5 September 2012; Accepted 12 October 2012

Academic Editor: Irma Virant-Klun

Copyright © 2013 Deepa Bhartiya et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. G. B. Zhou, Q. G. Meng, and N. Li, “In vitro derivation of germ cells from embryonic stem cells in mammals,” Molecular Reproduction and Development, vol. 77, no. 7, pp. 586–594, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. A. I. Marques-Mari, O. Lacham-Kaplan, J. V. Medrano, A. Pellicer, and C. Simón, “Differentiation of germ cells and gametes from stem cells,” Human Reproduction Update, vol. 15, no. 3, pp. 379–390, 2009. View at Publisher · View at Google Scholar · View at Scopus
  3. S. Panula, J. V. Medrano, K. Kee et al., “Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells,” Human Molecular Genetics, vol. 20, no. 4, pp. 752–762, 2011. View at Publisher · View at Google Scholar · View at Scopus
  4. K. Nayernia, J. H. Lee, N. Drusenheimer et al., “Derivation of male germ cells from bone marrow stem cells,” Laboratory Investigation, vol. 86, no. 7, pp. 654–663, 2006. View at Publisher · View at Google Scholar · View at Scopus
  5. Y. A. R. White, D. C. Woods, Y. Takai, O. Ishihara, H. Seki, and J. L. Tilly, “Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women,” Nature Medicine, vol. 18, no. 3, pp. 413–421, 2012. View at Publisher · View at Google Scholar
  6. H. Du and H. S. Taylor, “Stem cells and reproduction,” Current Opinion in Obstetrics and Gynecology, vol. 22, no. 3, pp. 235–241, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. M. Kanatsu-Shinohara, K. Inoue, J. Lee et al., “Generation of pluripotent stem cells from neonatal mouse testis,” Cell, vol. 119, no. 7, pp. 1001–1012, 2004. View at Publisher · View at Google Scholar · View at Scopus
  8. K. Guan, K. Nayernia, L. S. Maier et al., “Pluripotency of spermatogonial stem cells from adult mouse testis,” Nature, vol. 440, no. 7088, pp. 1199–1203, 2006. View at Publisher · View at Google Scholar · View at Scopus
  9. M. Seandel, D. James, S. V. Shmelkov et al., “Generation of functional multipotent adult stem cells from GPR125+ germline progenitors,” Nature, vol. 449, no. 7160, pp. 346–350, 2007. View at Publisher · View at Google Scholar · View at Scopus
  10. S. Conrad, M. Renninger, J. Hennenlotter et al., “Generation of pluripotent stem cells from adult human testis,” Nature, vol. 456, no. 7220, pp. 344–349, 2008. View at Publisher · View at Google Scholar · View at Scopus
  11. N. Golestaneh, M. Kokkinaki, D. Pant et al., “Pluripotent stem cells derived from adult human testes,” Stem Cells and Development, vol. 18, no. 8, pp. 1115–1125, 2009. View at Publisher · View at Google Scholar · View at Scopus
  12. N. Kossack, J. Meneses, S. Shefi et al., “Isolation and characterization of pluripotent human spermatogonial stem cell-derived cells,” Stem Cells, vol. 27, no. 1, pp. 138–149, 2009. View at Publisher · View at Google Scholar · View at Scopus
  13. S. C. Mizrak, J. V. Chikhovskaya, H. Sadri-Ardekani et al., “Embryonic stem cell-like cells derived from adult human testis,” Human Reproduction, vol. 25, no. 1, pp. 158–167, 2010. View at Publisher · View at Google Scholar · View at Scopus
  14. S. P. Gong, S. T. Lee, E. J. Lee et al., “Embryonic stem cell-like cells established by culture of adult ovarian cells in mice,” Fertility and Sterility, vol. 93, no. 8, pp. 2594–2601.e9, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. I. Virant-Klun, N. Zech, P. Rozman, et al., “Putative stem cells with an embryonic character isolated from the ovarian surface epithelium of women with no naturally present follicles and oocytes,” Differentiation, vol. 76, no. 8, pp. 843–856, 2008. View at Publisher · View at Google Scholar · View at Scopus
  16. I. Virant-Klun, P. Rožman, B. Cvjeticanin et al., “Parthenogenetic embryo-like structures in the human ovarian surface epithelium cell culture in postmenopausal women with no naturally present follicles and oocytes,” Stem Cells and Development, vol. 18, no. 1, pp. 137–150, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. S. Parte, D. Bhartiya, J. Telang et al., “Detection, characterization, and spontaneous differentiation in vitro of very small embryonic-like putative stem cells in adult mammalian ovary,” Stem Cells and Development, vol. 20, no. 8, pp. 1451–1464, 2011. View at Publisher · View at Google Scholar
  18. K. Zou, Z. Yuan, Z. Yang et al., “Production of offspring from a germline stem cell line derived from neonatal ovaries,” Nature Cell Biology, vol. 11, no. 5, pp. 631–636, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. D. Bhartiya, S. Kasiviswanathan, S. K. Unni et al., “Newer insights into premeiotic development of germ cells in adult human testis using Oct-4 as a stem cell marker,” Journal of Histochemistry and Cytochemistry, vol. 58, no. 12, pp. 1093–1106, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. D. Bhartiya, S. Kasiviswananthan, and A. Shaikh, “Cellular origin of testis-derived pluripotent stem cells: a case for very small embryonic-like stem cells,” Stem Cells and Development, vol. 21, no. 5, pp. 670–674, 2012. View at Publisher · View at Google Scholar
  21. M. de Felici, “Germ stem cells in the mammalian adult ovary: considerations by a fan of the primordial germ cells,” Molecular Human Reproduction, vol. 16, no. 9, pp. 632–636, 2010. View at Publisher · View at Google Scholar · View at Scopus
  22. A. McLaren and M. C. De Lopes, “Primordial germ cells in mouse and human,” in Essentials of Stem Cell Biology, R. Lanza, J. Gearhart, B. Hogan et al., Eds., pp. 131–136, 2009.
  23. A. G. Byskov, P. E. Høyer, C. Yding Andersen, S. G. Kristensen, A. Jespersen, and K. Møllgård, “No evidence for the presence of oogonia in the human ovary after their final clearance during the first two years of life,” Human Reproduction, vol. 26, no. 8, pp. 2129–2139, 2011. View at Publisher · View at Google Scholar · View at Scopus
  24. M. Z. Ratajczak, M. Kucia, M. Majka, R. Reca, and J. Ratajczak, “Heterogeneous populations of bone marrow stem cells—are we spotting on the same cells from the different angles?” Folia Histochemica et Cytobiologica, vol. 42, no. 3, pp. 139–146, 2004. View at Scopus
  25. M. Z. Ratajczak, E. Zuba-Surma, M. Kucia, A. Poniewierska, M. Suszynska, and J. Ratajczak, “Pluripotent and multipotent stem cells in adult tissues,” Advances in Medical Sciences, vol. 57, no. 1, pp. 1–17, 2012. View at Publisher · View at Google Scholar
  26. E. K. Zuba-Surma, M. Kucia, W. Wu et al., “Very small embryonic-like stem cells are present in adult murine organs: imageStream-based morphological analysis and distribution studies,” Cytometry Part A, vol. 73, no. 12, pp. 1116–1127, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. E. K. Zuba-Surma, W. Wu, J. Ratajczak, M. Kucia, and M. Z. Ratajczak, “Very small embryonic-like stem cells in adult tissues-Potential implications for aging,” Mechanisms of Ageing and Development, vol. 130, no. 1-2, pp. 58–66, 2009. View at Publisher · View at Google Scholar · View at Scopus
  28. D. M. Shin, E. K. Zuba-Surma, W. Wu et al., “Novel epigenetic mechanisms that control pluripotency and quiescence of adult bone marrow-derived Oct4+ very small embryonic-like stem cells,” Leukemia, vol. 23, no. 11, pp. 2042–2051, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. M. Z. Ratajczak, B. Machalinski, W. Wojakowski, J. Ratajczak, and M. Kucia, “A hypothesis for an embryonic origin of pluripotent Oct-4+ stem cells in adult bone marrow and other tissues,” Leukemia, vol. 21, no. 5, pp. 860–867, 2007. View at Publisher · View at Google Scholar · View at Scopus
  30. M. Kucia, R. Reca, F. R. Campbell et al., “A population of very small embryonic-like (VSEL) CXCR4+ SSEA-1+Oct-4+ stem cells identified in adult bone marrow,” Leukemia, vol. 20, no. 5, pp. 857–869, 2006. View at Publisher · View at Google Scholar · View at Scopus
  31. D. Bhartiya, “Pluripotent very small embryonic-like stem cells get discarded during cord blood and bone marrow processing,” Stem Cells and Development, vol. 21, no. 14, pp. 2563–2564, 2012. View at Publisher · View at Google Scholar
  32. D. Bhartiya, A. Shaikh, P. Nagvenkar et al., “Very small embryonic-like stem cells with maximum regenerative potential get discarded during cord blood banking and bone marrow processing for autologous stem cell therapy,” Stem Cells and Development, vol. 21, no. 1, pp. 1–6, 2012. View at Publisher · View at Google Scholar
  33. N. Li and H. Clevers, “Coexistence of quiescent and active adult stem cells in mammals,” Science, vol. 327, no. 5965, pp. 542–545, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. M. Z. Ratajczak, D. M. Shin, and M. Kucia, “Very small embryonic/epiblast-like stem cells: a missing link to support the germ line hypothesis of cancer development?” American Journal of Pathology, vol. 174, no. 6, pp. 1985–1992, 2009. View at Publisher · View at Google Scholar · View at Scopus
  35. M. Z. Ratajczak, D. M. Shin, R. Liu et al., “Epiblast/Germ line hypothesis of cancer development revisited: lesson from the presence of Oct-4+ cells in adult tissues,” Stem Cell Reviews and Reports, vol. 6, no. 2, pp. 307–316, 2010. View at Publisher · View at Google Scholar · View at Scopus
  36. E. K. Zuba-Surma, W. Wojakowski, M. Z. Ratajczak, and B. Dawn, “Very small embryonic-like stem cells: biology and therapeutic potential for heart repair,” Antioxidants and Redox Signaling, vol. 15, no. 7, pp. 1821–1834, 2011. View at Publisher · View at Google Scholar
  37. W. Wojakowski, M. Kucia, E. Zuba-Surma et al., “Very small embryonic-like stem cells in cardiovascular repair,” Pharmacology and Therapeutics, vol. 129, no. 1, pp. 21–28, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. E. Paczkowska, M. Kucia, D. Koziarska et al., “Clinical evidence that very small embryonic-like stem cells are mobilized into peripheral blood in patients after stroke,” Stroke, vol. 40, no. 4, pp. 1237–1244, 2009. View at Publisher · View at Google Scholar · View at Scopus
  39. J. Drukała, E. Paczkowska, M. Kucia et al., “Stem cells, including a population of very small embryonic-like stem cells, are mobilized into peripheral blood in patients after skin burn injury,” Stem Cell Reviews and Reports, vol. 8, no. 1, pp. 184–194, 2012. View at Publisher · View at Google Scholar · View at Scopus
  40. J. Ratajczak, E. Zuba-Surma, E. Paczkowska, M. Kucia, P. Nowacki, and M. Z. Ratajczak, “Stem cells for neural regeneration—a potential application of very small embryonic-like stem cells,” Journal of Physiology and Pharmacology, vol. 62, no. 1, pp. 3–11, 2011. View at Scopus
  41. D. Bhartiya, K. Sriraman, and S. Parte, “Stem cell interaction with somatic niche may hold the key to fertility restoration in cancer patients,” Obstetrics and Gynecology International, vol. 2012, Article ID 921082, 11 pages, 2012. View at Publisher · View at Google Scholar
  42. M. Pesce and H. R. Schöler, “Oct-4: gatekeeper in the beginnings of mammalian development,” Stem Cells, vol. 19, no. 4, pp. 271–278, 2001. View at Scopus
  43. S. Stefanovic and M. Pucéat, “Oct-3/4: not just a gatekeeper of pluripotency for embryonic stem cell, a cell fate instructor through a gene dosage effect,” Cell Cycle, vol. 6, no. 1, pp. 8–10, 2007. View at Scopus
  44. J. Kehler, E. Tolkunova, B. Koschorz et al., “Oct4 is required for primordial germ cell survival,” EMBO Reports, vol. 5, no. 11, pp. 1078–1083, 2004. View at Publisher · View at Google Scholar · View at Scopus
  45. J. Lee, H. K. Kim, J. Y. Rho, Y. M. Han, and J. Kim, “The human OCT-4 isoforms differ in their ability to confer self-renewal,” The Journal of Biological Chemistry, vol. 281, no. 44, pp. 33554–33565, 2006. View at Publisher · View at Google Scholar · View at Scopus
  46. S. Liedtke, J. Enczmann, S. Waclawczyk, P. Wernet, and G. Kögler, “Oct4 and its pseudogenes confuse stem cell research,” Cell Stem Cell, vol. 1, no. 4, pp. 364–366, 2007. View at Publisher · View at Google Scholar · View at Scopus
  47. S. Liedtke, M. Stephan, and G. Kögler, “Oct4 expression revisited: potential pitfalls for data misinterpretation in stem cell research,” Biological Chemistry, vol. 389, no. 7, pp. 845–850, 2008. View at Publisher · View at Google Scholar · View at Scopus
  48. X. Wang and J. Dai, “Concise review: isoforms of OCT4 contribute to the confusing diversity in stem cell biology,” Stem Cells, vol. 28, no. 5, pp. 885–893, 2010. View at Publisher · View at Google Scholar · View at Scopus
  49. J. Takeda, S. Seino, and G. I. Bell, “Human Oct3 gene family: CDNA sequences, alternative splicing, gene organization, chromosomal location, and expression at low levels in adult tissues,” Nucleic Acids Research, vol. 20, no. 17, pp. 4613–4620, 1992. View at Scopus
  50. C. J. Lengner, F. D. Camargo, K. Hochedlinger et al., “Oct4 expression is not required for mouse somatic stem cell self-renewal,” Cell Stem Cell, vol. 1, no. 4, pp. 403–415, 2007. View at Publisher · View at Google Scholar · View at Scopus
  51. C. J. Lengner, G. G. Welstead, and Rudolf Jaenisch, “The pluripotency regulator Oct4: a role in somatic stem cells?” Cell Cycle, vol. 7, no. 6, pp. 725–728, 2008. View at Scopus
  52. J. S. Berg and M. A. Goodell, “An argument against a role for Oct4 in somatic stem cells,” Cell Stem Cell, vol. 1, no. 4, pp. 359–360, 2007. View at Publisher · View at Google Scholar · View at Scopus
  53. J. Johnson, J. Bagley, M. Skaznik-Wikiel et al., “Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood,” Cell, vol. 122, no. 2, pp. 303–315, 2005. View at Publisher · View at Google Scholar · View at Scopus
  54. M. Kucia, B. Dawn, G. Hunt et al., “Cells expressing early cardiac markers reside in the bone marrow and are mobilized into the peripheral blood after myocardial infarction,” Circulation Research, vol. 95, no. 12, pp. 1191–1199, 2004. View at Publisher · View at Google Scholar · View at Scopus
  55. N. Beaujean, J. Taylor, J. Gardner, et al., “Effect of limited DNA methylation reprogramming in the normal sheep embryo on somatic cell nuclear transfer,” Biology of Reproduction, vol. 71, no. 1, pp. 185–193, 2004.
  56. J. Ehmcke and S. Schlatt, “A revised model for spermatological expansion in man: lessons from non-human primates,” Reproduction, vol. 132, no. 5, pp. 673–680, 2006. View at Publisher · View at Google Scholar · View at Scopus
  57. T. M. Plant, “Undifferentiated primate spermatogonia and their endocrine control,” Trends in Endocrinology and Metabolism, vol. 21, no. 8, pp. 488–495, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. Y. Clermont, “Renewal of spermatogonia in man,” American Journal of Anatomy, vol. 118, no. 2, pp. 509–524, 1966. View at Scopus
  59. J. V. Medrano, A. I. Marqués-Marí, C. E. Aguilar et al., “Comparative analysis of the germ cell markers c-KIT, SSEA-1 and VASA in testicular biopsies from secretory and obstructive azoospermias,” Molecular Human Reproduction, vol. 16, no. 11, pp. 811–817, 2010. View at Publisher · View at Google Scholar · View at Scopus
  60. D. C. Woods and J. L. Tilly, “The next (re)generation of ovarian biology and fertility in women: is current science tomorrow's practice?” Fertility and Sterility, vol. 98, no. 1, pp. 3–10, 2012. View at Publisher · View at Google Scholar
  61. E. Notarianni, “Reinterpretation of evidence advanced for neo-oogenesis in mammals, in terms of a finite oocyte reserve,” Journal of Ovarian Research, vol. 4, no. 1, article 1, 2011. View at Publisher · View at Google Scholar · View at Scopus
  62. P. P. Szotek, H. L. Chang, K. Brennand et al., “Normal ovarian surface epithelial label-retaining cells exhibit stem/progenitor cell characteristics,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 34, pp. 12469–12473, 2008. View at Publisher · View at Google Scholar · View at Scopus
  63. A. G. Byskov, “Reply: the continued presence of stem cells and oogonia in the adult mammalian ovary,” Human Reproduction, vol. 27, no. 3, pp. 938–939, 2012. View at Publisher · View at Google Scholar
  64. S. K. Unni, D. N. Modi, S. G. Pathak, J. V. Dhabalia, and D. Bhartiya, “Stage-specific localization and expression of c-kit in the adult human testis,” Journal of Histochemistry and Cytochemistry, vol. 57, no. 9, pp. 861–869, 2009. View at Publisher · View at Google Scholar · View at Scopus
  65. H. Zhang, W. Zheng, Y. Shen, D. Adhikari, H. Ueno, and K. Liu, “Experimental evidence showing that no mitotically active female germline progenitors exist in postnatal mouse ovaries,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 31, pp. 12580–12585, 2012. View at Publisher · View at Google Scholar
  66. D. H. Castrillon, B. J. Quade, T. Y. Wang, C. Quigley, and C. P. Crum, “The human VASA gene is specifically expressed in the germ cell lineage,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 17, pp. 9585–9590, 2000. View at Scopus
  67. Y. Fujiwara, T. Komiya, H. Kawabata 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,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 25, pp. 12258–12262, 1994. View at Publisher · View at Google Scholar · View at Scopus
  68. Y. Liu, C. Wu, Q. Lyu et al., “Germline stem cells and neo-oogenesis in the adult human ovary,” Developmental Biology, vol. 306, no. 1, pp. 112–120, 2007. View at Publisher · View at Google Scholar · View at Scopus
  69. R. Schofield, “The relationship between the spleen colony-forming cell and the haemopoietic stem cell. A hypothesis,” Blood Cells, vol. 4, no. 1-2, pp. 7–25, 1978. View at Scopus
  70. D. L. Jones and T. A. Rando, “Emerging models and paradigms for stem cell ageing,” Nature Cell Biology, vol. 13, no. 5, pp. 506–512, 2011. View at Publisher · View at Google Scholar · View at Scopus
  71. X. Zhang, K. T. Ebata, B. Robaire, and M. C. Nagano, “Aging of male germ line stem cells in mice,” Biology of Reproduction, vol. 74, no. 1, pp. 119–124, 2006. View at Publisher · View at Google Scholar · View at Scopus
  72. M. Boyle, C. Wong, M. Rocha, and D. L. Jones, “Decline in self-renewal factors contributes to aging of the stem cell niche in the Drosophila testis,” Cell Stem Cell, vol. 1, no. 4, pp. 470–478, 2007. View at Publisher · View at Google Scholar · View at Scopus
  73. B. Y. Ryu, K. E. Orwig, J. M. Oatley, M. R. Avarbock, and R. L. Brinster, “Effects of aging and niche microenvironment on spermatogonial stem cell self-renewal,” Stem Cells, vol. 24, no. 6, pp. 1505–1511, 2006. View at Publisher · View at Google Scholar · View at Scopus
  74. S. J. Richardson, V. Senikas, and J. F. Nelson, “Follicular depletion during the menopausal transition: evidence for accelerated loss and ultimate exhaustion,” Journal of Clinical Endocrinology and Metabolism, vol. 65, no. 6, pp. 1231–1237, 1987. View at Scopus
  75. W. H. Wallace and T. W. Kelsey, “Human ovarian reserve from conception to the menopause,” PloS ONE, vol. 5, no. 1, Article ID e8772, 2010. View at Publisher · View at Google Scholar · View at Scopus
  76. R. G. Gosden, S. C. Laing, and L. S. Felicio, “Imminent oocyte exhaustion and reduced follicular recruitment mark the transition to acyclicity in aging C57BL/6J mice,” Biology of Reproduction, vol. 28, no. 2, pp. 255–260, 1983. View at Scopus
  77. K. Oktay and O. Oktem, “Regeneration of oocytes after chemotherapy: connecting the evidence from mouse to human,” Journal of Clinical Oncology, vol. 25, no. 22, pp. 3185–3187, 2007. View at Publisher · View at Google Scholar · View at Scopus
  78. E. Massasa, X. S. Costa, and H. S. Taylor, “Failure of the stem cell niche rather than loss of oocyte stem cells in the aging ovary,” Aging, vol. 2, no. 1, pp. 1–2, 2010. View at Scopus
  79. A. Bukovsky, “Oogenesis from human somatic stem cells and a role of immune adaptation in premature ovarian failure,” Current Stem Cell Research & Therapy, vol. 1, no. 3, pp. 289–303, 2006. View at Scopus
  80. A. Bukovsky, “How can female germline stem cells contribute to the physiological neo-oogenesis in mammals and why menopause occurs?” Microscopy and Microanalysis, vol. 17, no. 4, pp. 498–505, 2011. View at Publisher · View at Google Scholar · View at Scopus
  81. H. J. Lee, K. Selesniemi, Y. Niikura et al., “Bone marrow transplantation generates immature oocytes and rescues long-term fertility in a preclinical mouse model of chemotherapy-induced premature ovarian failure,” Journal of Clinical Oncology, vol. 25, no. 22, pp. 3198–3204, 2007. View at Publisher · View at Google Scholar · View at Scopus
  82. Y. Niikura, T. Niikura, and J. L. Tilly, “Aged mouse ovaries possess rare premeiotic germ cells that can generate oocytes following transplantation into a young host environment,” Aging, vol. 1, no. 12, pp. 971–978, 2009. View at Scopus
  83. V. N. Anisimov, “Biology of aging and cancer,” Cancer Control, vol. 14, no. 1, pp. 23–31, 2007. View at Scopus
  84. F. Zhang, Q. Yan, W. Yan, H. Cheng, Y. Hui, and Q. Li, “Cancer is a disease of unregulated expansion of somatic stem cells resulting from disrupted asymmetric division,” Medical Hypotheses, vol. 70, no. 1, pp. 208–209, 2008. View at Publisher · View at Google Scholar · View at Scopus
  85. M. A. Rijlaarsdam, H. A. D. M. Van Herk, A. J. M. Gillis et al., “Specific detection of OCT3/4 isoform A/B/B1 expression in solid (germ cell) tumours and cell lines: confirmation of OCT3/4 specificity for germ cell tumours,” British Journal of Cancer, vol. 105, no. 6, pp. 854–863, 2011. View at Publisher · View at Google Scholar
  86. L. H. J. Looijenga, H. Stoop, H. P. J. C. De Leeuw et al., “POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors,” Cancer Research, vol. 63, no. 9, pp. 2244–2250, 2003. View at Scopus
  87. M. Cools, H. Stoop, A. M. F. Kersemaekers et al., “Gonadoblastoma arising in undifferentiated gonadal tissue within dysgenetic gonads,” Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 6, pp. 2404–2413, 2006. View at Publisher · View at Google Scholar · View at Scopus
  88. M. Cools, K. Van Aerde, A. M. Kersemaekers et al., “Morphological and immunohistochemical differences between gonadal maturation delay and early germ cell neoplasia in patients with undervirilization syndromes,” Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 9, pp. 5295–5303, 2005. View at Publisher · View at Google Scholar · View at Scopus
  89. W. J. Murdoch and A. C. McDonnel, “Roles of the ovarian surface epithelium in ovulation and carcinogenesis,” Reproduction, vol. 123, no. 6, pp. 743–750, 2002. View at Scopus
  90. C. K. Bose, “Follicle stimulating hormone receptor in ovarian surface epithelium and epithelial ovarian cancer,” Oncology Research, vol. 17, no. 5, pp. 231–238, 2008. View at Publisher · View at Google Scholar · View at Scopus
  91. X. Chen, J. Aravindakshan, Y. Yang, and M. R. Sairam, “Early alterations in ovarian surface epithelial cells and induction of ovarian epithelial tumors triggered by loss of FSH receptor,” Neoplasia, vol. 9, no. 6, pp. 521–531, 2007. View at Publisher · View at Google Scholar · View at Scopus
  92. T. B. L. Kirkwood, “Evolution of ageing,” Nature, vol. 270, no. 5635, pp. 301–304, 1977. View at Publisher · View at Google Scholar · View at Scopus
  93. M. Z. Ratajczak, D. M. Shin, J. Ratajczak, et al., “A novel insight into aging: are there pluripotent very small embryonic-like stem cells (VSELs) in adult tissues overtime depleted in an Igf-1-dependent manner?” Aging, vol. 2, no. 11, pp. 875–883, 2010.
  94. J. E. Burdette, S. J. Kurley, S. M. Kilen, K. E. Mayo, and T. K. Woodruff, “Gonadotropin-induced superovulation drives ovarian surface epithelia proliferation in CD1 mice,” Endocrinology, vol. 147, no. 5, pp. 2338–2345, 2006. View at Publisher · View at Google Scholar · View at Scopus