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Oogenesis in adult mammals, including humans

A review

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Abstract

The origin of oocytes and primary follicles in ovaries of adult mammalian females has been a matter of dispute for over 100 yr. The prevailing belief that all oocytes in adult mammalian females must persist from the fetal period of life seems to be a uniquely retrogressive reproductive mechanism requiring humans to preserve their gametes from the fetal period for several decades. The utilization of modern techniques during last 10 yr clearly demonstrates that mammalian primordial germ cells originate from somatic cell precursors. This indicates that if somatic cells are precursors of germ cells, then somatic mutations can be passed on to progeny. Mitotically active germline stem cells have been described earlier in ovaries of adult prosimian primates and recently have been reported to also be present in the ovaries of adult mice. We have earlier shown that in adult human females, mesenchymal cells in the ovarian tunica albuginea undergo a mesenchymal-epithelial transition into ovarian surface epithelium cells, which differentiate sequentially into primitive granulosa and germ cells. Recently, we have reported that these structures assemble in the deeper ovarian cortex and form new follicles to replace earlier primary follicles undergoing atresia (follicular renewal). Our current observations also indicate that follicular renewal exists in rat ovaries, and human oocytes can differentiate from ovarian surface epithelium in fetal ovaries in vivo and from adult ovaries in vitro. These reports challenge the established dogma regarding the fetal origin of eggs and primary follicles in adult mammalian ovaries. Our data indicate that the pool of primary follicles in adult human ovaries does not represent a static but a dynamic population of differentiating and regressing structures. Yet, the follicular renewal may cease at a certain age, and this may predetermine the onset of the natural menopause or premature ovarian failure. A lack of follicular renewal in aging ovaries may cause an accumulation of spontaneously arising or environmentally induced genetic alterations of oocytes, and that may be why aging females have a much higher chance of having oocytes with more mutations in persisting primary follicles.

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References

  1. Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., and Walter, P. (2002). Molecular biology of the cell. Garland Science: New York.

    Google Scholar 

  2. Allen, E. (1923). Am. J. Anat. 31, 439–481.

    Article  Google Scholar 

  3. Auersperg, N., Pan, J., Grove, B. D., et al. (1999). Proc. Natl. Acad. Sci. USA 96, 6249–6254.

    Article  PubMed  CAS  Google Scholar 

  4. Auersperg, N., Wong, A. S., Choi, K. C., Kang, S. K., and Leung, P. C. (2001). Endocr. Rev. 22, 255–288.

    Article  PubMed  CAS  Google Scholar 

  5. Baker, T. G. (1972). In: Reproductive biology. Balin, H. and Glasser S. (eds.). Excerpta Medica: Amsterdam, pp. 398–437.

    Google Scholar 

  6. Barclay, A. N., Letarte-Muirhead, M., Williams, A. F., and Faulkes, R. A. (1976). Nature 267, 563–567.

    Article  Google Scholar 

  7. Block, E. (1952). Acta Anat. (Basel) 14, 108–123.

    CAS  Google Scholar 

  8. Bousfield, G. R., Butnev, V. Y., Gotschall, R. R., Baker, V. L., and Moore, W. T. (1996). Mol. Cell Endocrinol. 125, 3–19.

    Article  PubMed  CAS  Google Scholar 

  9. Brambell, F. W. R. (1927). Proc. Roy. Soc. 101, 391–409.

    Article  Google Scholar 

  10. Bukovsky, A., Caudle, M. R., and Keenan, J. A. (1997). In: Microscopy of reproduction and development: a dynamic approach. Motta, P. M. (ed.) Antonio Delfino Editore: Roma, pp. 79–89.

    Google Scholar 

  11. Bukovsky, A., Caudle, M. R., Keenan, J. A., et al. (2001). BMC Dev. Biol. 1, 11.

    Article  PubMed  CAS  Google Scholar 

  12. Bukovsky, A., Caudle, M. R., Keenan, J. A., Wimalasena, J., Foster, J. S., and Van Meter, S. E. (1995). Biol. Reprod. 52, 776–792.

    Article  PubMed  CAS  Google Scholar 

  13. Bukovsky, A., Caudle, M. R., Keenan, J. A., Wimalasena, J., Upadhyaya, N. B., and Van Meter, S. E. (1995). Biol. Reprod. 53, 1373–1384.

    Article  PubMed  CAS  Google Scholar 

  14. Bukovsky, A., Caudle, M. R., Keenan, J. A., Wimalasena, J., Upadhyaya, N. B., and Van Meter, S. E. (1996). Am. J. Reprod. Immunol. 36, 327–341.

    PubMed  CAS  Google Scholar 

  15. Bukovsky, A., Caudle, M. R., Svetlikova, M., and Upadhyaya, N. B. (2004). Reprod. Biol. Endocrinol. 2, 20.

    Article  PubMed  Google Scholar 

  16. Bukovsky, A., Indrapichate, K., Fujiwara, H., et al. (2003). Reprod. Biol. Endocrinol. 1, 46.

    Article  PubMed  Google Scholar 

  17. Bukovsky, A., Keenan, J. A., Caudle, M. R., Wimalasena, J., Upadhyaya, N. B., and Van Meter, S. E. (1995). Am. J. Reprod. Immunol. 33, 323–340.

    PubMed  CAS  Google Scholar 

  18. Bukovsky, A., Svetlikova, M., and Caudle, M. R. (2005). Reprod. Biol. Endocrinol. 3, 17.

    Article  PubMed  CAS  Google Scholar 

  19. Butler, H. and Juma, M. B. (1970). Nature 226, 552–553.

    Article  PubMed  CAS  Google Scholar 

  20. Byskov, A. G., Skakkebaek, N. E., Stafanger, G., and Peters, H. (1997). J. Anat. 123, 77–86.

    Google Scholar 

  21. Carlson, J. L., Bakst, M. R., and Ottinger, M. A. (1996). Poult. Sci. 75, 1569–1578.

    PubMed  CAS  Google Scholar 

  22. Choi, K. C., Auersperg, N., and Leung, P. C. (2003). Reprod. Biol. Endocrinol. 1, 71.

    Article  PubMed  Google Scholar 

  23. Cohen, F. E., Novotny, J., Sternberg, M. J. E., Campbell, D. G., and Williams, A. F. (1981). Biochem. J. 195, 31–40.

    PubMed  CAS  Google Scholar 

  24. Cox, R. T. and Spradling, A. C. (2003). Development 130, 1579–1590.

    Article  PubMed  CAS  Google Scholar 

  25. Czernobilsky, B., Moll, R., Levy, R., and Franke, W. W. (1985). Eur. J. Cell Biol. 37, 175–190.

    PubMed  CAS  Google Scholar 

  26. David, G. F., Anand Kumar, T. C., and Baker, T. G. (1974). J. Reprod. Fertil. 41, 447–451.

    Article  PubMed  CAS  Google Scholar 

  27. de Winiwarter, H. (1901). Arch. Biol. Paris 17, 33–199.

    Google Scholar 

  28. Dunbar, B. S., Timmons, T. M., Skinner, S. M., and Prasad, S. V. (2001). Biol. Reprod. 65, 951–960.

    Article  PubMed  CAS  Google Scholar 

  29. Dyck, H. G., Hamilton, T. C., Godwin, A. K., Lynch, H. T., Maines-Bandiera, S., and Auersperg, N. (1996). Int. J. Cancer 69, 429–436.

    Article  PubMed  CAS  Google Scholar 

  30. Edelman, G. M. (1988). Biochemistry 27, 3533–3543.

    Article  PubMed  CAS  Google Scholar 

  31. Erickson, B. H. (1966). J. Anim. Sci. 25, 800–805.

    PubMed  CAS  Google Scholar 

  32. Erickson, G. F. and Shimasaki, S. (2003). Reprod. Biol. Endocrinol. 1, 9.

    Article  PubMed  Google Scholar 

  33. Evans, H. M. and Swezy, O. (1931). Mem. Univ. Calif. 9, 119–224.

    Google Scholar 

  34. Everett, N. B. (1943). J. Exp. Zool. 92, 49–91.

    Article  Google Scholar 

  35. Franchi, L. L., Mandl, A. M., and Zuckerman, S. (1962). In: The ovary. Zuckerman, S. (ed.). Academic Press: London, pp. 1–88.

    Google Scholar 

  36. Geijsen, N., Horoschak, M., Kim, K., Gribnau, J., Eggan, K., and Daley, G. Q. (2004). Nature 427, 148–154.

    Article  PubMed  CAS  Google Scholar 

  37. Ginsburg, M., Snow, M. H., and McLaren, A. (1990). Development 110, 521–528.

    PubMed  CAS  Google Scholar 

  38. Gosden, R. G. (2004). Hum. Reprod. Update 10, 193–195.

    Article  PubMed  Google Scholar 

  39. Gougeon, A., Echochard, R., and Thalabard, J. C. (1994). Biol. Reprod. 50, 653–663.

    Article  PubMed  CAS  Google Scholar 

  40. Hershkovitz, R., Erez, O., Sheiner, E., Landau, D., Mankuta, D., and Mazor, M. (2003). Acta Obstet. Gynecol. Scand. 82, 22–27.

    Article  PubMed  Google Scholar 

  41. Hubner, K., Fuhrmann, G., Christenson, L. K., et al. (2003). Science 300, 1251–1256.

    Article  PubMed  CAS  Google Scholar 

  42. Ingram, D. L. (1962). In: The ovary. Zuckerman, S. (ed.). Academic Press: London, pp. 247–273.

    Google Scholar 

  43. Ioannou, J. M. (1968). J. Embryol. Exp. Morphol. 17, 139–145.

    Google Scholar 

  44. Johnson, J., Canning, J., Kaneko, T., Pru, J. K., and Tilly, J. L. (2004). Nature 428, 145–150.

    Article  PubMed  CAS  Google Scholar 

  45. Kelly, S. J. (1977). J. Exp. Zool. 200, 365–376.

    Article  PubMed  CAS  Google Scholar 

  46. Kingery, H. M. (1917). J. Morphol. 30, 261–315.

    Article  Google Scholar 

  47. Lawson, K. A., Dunn, N. R., Roelen, B. A., et al. (1999). Genes Dev. 13, 424–436.

    PubMed  CAS  Google Scholar 

  48. Lawson, K. A. and Hage, W. J. (1994). Ciba Found. Symp. 182, 68–84.

    PubMed  CAS  Google Scholar 

  49. Makabe, S., Iwaki, A., Hafez, E. S. E., and Motta, P. M. (1980). In: Biology of the ovary. Motta, P. M. and Hafez, E. S. E. (eds.). Martinus Nijhoff Publishers: The Hague, pp. 279–290.

    Google Scholar 

  50. Mathe, G. (1997). Biomed. Pharmacother. 51, 49–57.

    Article  PubMed  CAS  Google Scholar 

  51. McLaren, A. (1999). Genes Dev. 13, 373–376.

    PubMed  CAS  Google Scholar 

  52. Mossman, H. W. and Duke, K. L. (1973). In: Handbook of physiology, Sect. 7: endocrinology. Greep, R. O. (ed.). American Physiological Society: Washington, DC, pp. 389–402.

    Google Scholar 

  53. Motta, P. M. and Makabe, S. (1986). J. Submicrosc. Cytol. 18, 271–290.

    PubMed  CAS  Google Scholar 

  54. Motta, P. M., Makabe, S., Naguro, T., and Correr, S. (1994). Arch. Histol. Cytol. 57, 369–394.

    PubMed  CAS  Google Scholar 

  55. Motta, P. M., Nottola, S. A., Makabe, S., and Heyn, R. (2000). Hum. Reprod. 15(Suppl. 2), 129–147.

    PubMed  Google Scholar 

  56. Motta, P. M., Van Blerkom, J., and Makabe, S. (1980). J. Submicrosc. Cytol. 12, 407–425.

    Google Scholar 

  57. Page-Roberts, B. A. (1972). Invest. Urol. 9, 385–389.

    PubMed  CAS  Google Scholar 

  58. Pan, J. and Auersperg, N. (1998). Biochem. Cell Biol. 76, 27–35.

    Article  PubMed  CAS  Google Scholar 

  59. Penny, R., Olambiwonnu, O., and Frasier, S. D. (1976). Pediatrics 58, 110–114.

    PubMed  CAS  Google Scholar 

  60. Pepling, M. E. and Spradling, A. C. (1998). Development 125, 3323–3328.

    PubMed  CAS  Google Scholar 

  61. Pepling, M. E. and Spradling, A. C. (2001). Dev. Biol. 234, 339–351.

    Article  PubMed  CAS  Google Scholar 

  62. Peters, H. and McNatty, K. P. (1980). The ovary. a correlation of structure and function in mammals. University of California Press: Berkeley and Los Angeles, CA.

    Google Scholar 

  63. Picher, M., Burch, L. H., Hirsh, A. J., Spychala, J., and Boucher, R. C. (2003). J. Biol. Chem. 278, 13468–13479.

    Article  PubMed  CAS  Google Scholar 

  64. Prindull, G. and Zipori, D. (2004). Blood 103, 2892–2899.

    Article  PubMed  CAS  Google Scholar 

  65. Quinones, J. A. and van Bogaert, L. J. (1979). Acta Histochem. 64, 106–112.

    PubMed  CAS  Google Scholar 

  66. Richardson, R. T., Yamasaki, N., and O’Rand, M. G. (1994). Dev. Biol. 165, 688–701.

    Article  PubMed  CAS  Google Scholar 

  67. Santini, D., Ceccarelli, C., Mazzoleni, G., Pasquinelli, G., Jasonni, V. M., and Martinelli, G. N. (1993). Histochemistry 99, 311–319.

    Article  PubMed  CAS  Google Scholar 

  68. Simkins, C. S. (1932). J. Anat. 51, 465–505.

    Article  Google Scholar 

  69. Skinner, S. M. and Dunbar, B. S. (1992). J. Histochem. Cytochem. 40, 1031–1036.

    PubMed  CAS  Google Scholar 

  70. Skinner, S. M., Kieback, D. G., Chunn, J., et al. (1997). Anticancer Res. 17, 907–911.

    PubMed  CAS  Google Scholar 

  71. Skinner, S. M., Lee, V. H., Kieback, D. G., Jones, L. A., Kaplan, A. L., and Dunbar, B. S. (1997). Anticancer Res. 17, 901–906.

    PubMed  CAS  Google Scholar 

  72. Tam, P. P. and Zhou, S. X. (1996). Dev. Biol. 178, 124–132.

    Article  PubMed  CAS  Google Scholar 

  73. Treisman, R. (1996). Curr. Opin. Cell Biol. 8, 205–215.

    Article  PubMed  CAS  Google Scholar 

  74. Van Blerkom, J. and Motta, P. M. (1979). The cellular basis of mammalian reproduction. Urban & Schwarzenberg: Baltimore-Munich.

    Google Scholar 

  75. Waldeyer, W. (1996). In: Hanbuch der vergleichenden und experimentellen Entwicklung der Wirbeltiere. Hertwig, O. (ed.). Fisher: Jena, pp. 86–476.

    Google Scholar 

  76. Waldeyer, W. (1870). Eierstock und Ei. Engelmann, Leipig.

    Google Scholar 

  77. Wartenberg, H. (1983). Bibl. Anat. 24, 67–76.

    Google Scholar 

  78. Weissmann, A. (1885). Die Continuitat des Keimplasmas als Grundlage einer Theorie der Vererbung. Fischer-Verlag: Jena.

    Google Scholar 

  79. Williams, A. F. and Barclay, A. N. (1988). Annu. Rev. Immunol. 6, 381–405.

    PubMed  CAS  Google Scholar 

  80. Yamashita, J., Itoh, H., Hirashima, M., et al. (2000). Nature 408, 92–96.

    Article  PubMed  CAS  Google Scholar 

  81. Zamboni, L. (1970). Biol. Reprod. Suppl. 2, 44–63.

    Article  PubMed  CAS  Google Scholar 

  82. Ziomek, C. A., Lepire, M. L., and Torres, I. (1990). J. Histochem. Cytochem. 38, 437–442.

    PubMed  CAS  Google Scholar 

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Bukovsky, A., Caudle, M.R., Svetlikova, M. et al. Oogenesis in adult mammals, including humans. Endocr 26, 301–316 (2005). https://doi.org/10.1385/ENDO:26:3:301

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