Summary
The central thesis regarding the human ovaries is that, although primordial germ cells in embryonal ovaries are of extraovarian origin, those generated during the fetal period and in postnatal life are derived from the ovarian surface epithelium (OSE) bipotent cells. With the assistance of immune system-related cells, secondary germ cells and primitive granulosa cells originate from OSE stem cells in the fetal and adult human gonads. Fetal primary follicles are formed during the second trimester of intrauterine life, prior to the end of immune adaptation, possibly to be recognized as self-structures and renewed later. With the onset of menarche, a periodical oocyte and follicular renewal emerges to replace aging primary follicles and ensure that fresh eggs for healthy babies are always available during the prime reproductive period. The periodical follicular renewal ceases between 35 and 40 yr of age, and the remaining primary follicles are utilized during the premenopausal period until exhausted. However, the persisting oocytes accumulate genetic alterations and may become unsuitable for ovulation and fertilization. The human OSE stem cells preserve the character of embryonic stem cells, and they may produce distinct cell types, including new eggs in vitro, particularly when derived from patients with premature ovarian failure or aging and postmenopausal ovaries. Our observations also indicate that there are substantial differences in follicular renewal between adult human and rat ovaries. As part of this chapter, we present in detail protocols utilized to analyze oogenesis in humans and to study interspecies differences when compared to the ovaries of rat females.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
1. Allen, E. (1923) Ovogenesis during sexual maturity. Am. J. Anat. 31, 439–481.
2. Pearl, R., and Schoppe, W. F. (1921) Studies on the physiology of reproduction in the domestic fowl. XVIII. Further observations on the anatomical basis of fecundity. J. Exp. Zool. 34, 101–1189.
3. Zuckerman, S. (1951) The number of oocytes in the mature ovary. Recent Prog. Horm. Res. 6, 63–109.
4. Franchi, L. L., Mandl, A. M., and Zuckerman, S. (1962) The development of the ovary and the process of oogenesis, in The ovary (Zuckerman, S., ed.)—, Academic Press, London, pp. 1–88.
5. Zuckerman, S., and Baker, T. G. (1977) The development of the ovary and the process of oogenesis, in The ovary, Vol. 1 (Zuckerman, S., and Weir, B. J., eds.)—, Academic Press, New York, pp. 41–67.
6. Kingery, H. M. (1917) Oogenesis in the white mouse. J. Morphol. 30, 261–315.
7. Evans, H. M., and Swezy, O. (1931) Ovogenesis and the normal follicular cycle in adult mammalia. Mem. Univ. Calif. 9, 119–224.
8. Gerard, P. (1920) Contribution a l'etude de l'ovarie des mammiferes. L'ovaire de Galago mossambicus(Young). Arch. Biol. 43, 357–391.
9. Rao, C. R. N. (1928) On the structure of the ovary and the ovarian ovum of Loris lydekkeri-anus Cabr. Q. J. Micr. Sci. 71, 57–73.
10. Zuckerman, S., and Weir, B. J. (1977) The ovary, 2nd ed., Vol. I, -Academic Press, New York.
11. Bukovsky, A., Keenan, J. A., Caudle, M. R., Wimalasena, J., Upadhyaya, N. B., and Van Meter, S. E. (1995) Immunohistochemical studies of the adult human ovary: possible contribution of immune and epithelial factors to folliculogenesis. Am. J. Reprod. Immunol. 33, 323–340.
12. Bukovsky, A., Caudle, M. R., Svetlikova, M., and Upadhyaya, N. B. (2004) Origin of germ cells and formation of new primary follicles in adult human ovaries. Reprod. Biol. Endocrinol. 2, 20. Available at: http://www.rbej.com/content/2/1/20.
13. Bukovsky, A., Ayala, M. E., Dominguez, R., Svetlikova, M., and Selleck-White, R. (2007). Bone marrow derived cells and alternative pathways of oogenesis in adult rodents. Cell Cycle 6(18), 2306–2309.
14. Block, E. (1952). Quantitative morphological investigations of the follicular system in women. Variations at different ages. Acta Anat. (Basel). 14, 108–123.
15. Kerr, J. B., Duckett, R., Myers, M., Britt, K. L., Mladenovska, T., and Findlay, J. K. (2006) Quantification of healthy follicles in the neonatal and adult mouse ovary: evidence for maintenance of primordial follicle supply. Reproduction. 132, 95–109.
16. Johnson, J., Canning, J., Kaneko, T., Pru, J. K., and Tilly, J. L. (2004) Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature. 428, 145–150.
17. Gougeon, A., Echochard, R., and Thalabard, J. C. (1994) Age-related changes of the population of human ovarian follicles: increase in the disappearance rate of non-growing and early-growing follicles in aging women. Biol. Reprod. 50, 653–663.
18. Peters, H., and McNatty, K. P. (1980) The ovary. A correlation of structure and function in mammals, University of California Press, Berkeley, CA.
Waldeyer, W. (1870) Eierstock und Ei, Engelmann, Leipzig.
20. Simkins, C. S. (1928) Origin of the sex cells in man. Am. J. Anat. 41, 249–253.
21. Brambell, F. W. R. (1927) The development and morphology of the gonads of the mouse. Part 1. The morphogenesis of the indifferent gonad and of the ovary. Proc. R. Soc. 101, 391–409.
22. Motta, P. M., Van Blerkom, J., and Makabe, S. (1980) Changes in the surface morphology of ovarian “germinal” epithelium during the reproductive cycle and in some pathological conditions. J. Submicrosc. Cytol. 12, 407–425.
23. Bukovsky, A., Caudle, M. R., Svetlikova, M., Wimalasena, J., Ayala, M. E., and Dominguez, R. (2005) Oogenesis in adult mammals, including humans: a review. Endocrine. 26, 301–316.
24. Bukovsky, A., Copas, P., and Virant-Klun, I. (2006) Potential new strategies for the treatment of ovarian infertility and degenerative diseases with autologous ovarian stem cells. Expert Opin. Biol. Ther. 6, 341–365.
25. Williams, A. F., and Barclay, A. N. (1988) The immunoglobulin superfamily—domains for cell surface recognition. Annu. Rev. Immunol. 6, 381–405.
26. Bukovsky, A., Caudle, M. R., Keenan, J. A., et al. (2001) Association of mesenchymal cells and immunoglobulins with differentiating epithelial cells. BMC Dev. Biol. 1, 11.
27. Auersperg, N., Wong, A. S., Choi, K. C., Kang, S. K., and Leung, P. C. (2001) Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr. Rev. 22, 255–288.
28. Faddy, M. J. (2000) Follicle dynamics during ovarian ageing. Mol. Cell Endocrinol. 163, 43.
29. Bukovsky, A., Caudle, M. R., Keenan, J. A., Wimalasena, J., Foster, J. S., and Van Meter, S. E. (1995) Quantitative evaluation of the cell cycle-related retinoblastoma protein and localization of Thy-1 differentiation protein and macrophages during follicular development and atresia, and in human corpora lutea. Biol. Reprod. 52, 776–792.
30. Bukovsky, A. (2006) Immune system involvement in the regulation of ovarian function and augmentation of cancer. Microsc. Res. Tech. 69, 482–500.
31. Czernobilsky, B., Moll, R., Levy, R., and Franke, W. W. (1985) Co-expression of cytokeratin and vimentin filaments in mesothelial, granulosa and rete ovarii cells of the human ovary. Eur. J. Cell Biol. 37, 175–190.
32. Johnson, J., Bagley, J., Skaznik-Wikiel, M., et al. (2005) Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell. 122, 303–315.
33. Boja, E. S., Hoodbhoy, T., Garfield, M., and Fales, H. M. (2005) Structural conservation of mouse and rat zona pellucida glycoproteins. Probing the native rat zona pellucida proteome by mass spectrometry. Biochemistry. 44, 16445–16460.
34. Erickson, G. F., and Shimasaki, S. (2003) The spatiotemporal expression pattern of the bone morphogenetic protein family in rat ovary cell types during the estrous cycle. Reprod. Biol. Endocrinol. 1, 9.
35. Ingram, D. L. (1962) Atresia, in The ovary (Zuckerman, S., ed.), Academic Press, London, pp. 247–273.
36. Bukovsky, A., Svetlikova, M., and Caudle, M. R. (2005) Oogenesis in cultures derived from adult human ovaries. Reprod. Biol. Endocrinol. 3, 17.
37. Bukovsky, A., and Virant-Klun, I. (2006) Adult stem cells in the human ovary, in Stem cells in reproductive medicine: basic science and therapeutic potential (Simon, C., and Pellicer, A., eds,), Informa Healthcare, London, pp. 53–70.
38. Corrigan, E. C., Raygada, M. J., Vanderhoof, V. H., and Nelson, L. M. (2005) A woman with spontaneous premature ovarian failure gives birth to a child with fragile X syndrome. Fertil. Steril. 84, 1508.
39. Rebar, R. W. (2000) Premature ovarian failure, in Menopause biology and pathobiology (Lobo, R. A., Kesley, J., and Marcus, R., eds,), Academic Press, San Diego, CA, pp. 135–146.
40. Gersak, K., Meden-Vrtovec, H., and Peterlin, B. (2003) Fragile X premutation in women with sporadic premature ovarian failure in Slovenia. Hum. Reprod. 18, 1637–1640.
41. Sehgal, S., Gupta, S. K., and Bhatnagar, P. (1989) Long-term effects of immunization with porcine zona pellucida on rabbit ovaries. Pathology. 21, 105–110.
42. Miller, C. C., Fayrer-Hosken, R. A., Timmons, T. M., Lee, V. H., Caudle, A. B., and Dunbar, B. S. (1992) Characterization of equine zona pellucida glycoproteins by polyacrylamide gel electrophoresis and immunological techniques. J. Reprod. Fertil. 96, 815–825.
43. Horejsi, V., Hilgert, I., Kristofova, H., Bazil, V., Bukovsky, A., and Kulhankova, J. (1986) Monoclonal antibodies against human leucocyte antigens. I. Antibodies against beta-2-microglobulin, immunoglobulin kappa light chains, HLA-DR-like antigens, T8 antigen, T1 antigen, a monocyte antigen, and a pan-leucocyte antigen. Folia Biol. (Praha). 32, 12–25.
44. McKenzie, J. L., and Fabre, J. W. (1981) Human Thy-1: unusual localization and possible functional significance in lymphoid tissues. J. Immunol. 126, 843–850.
45. Yurewicz, E. C., Sacco, A. G., and Subramanian, M. G. (1987) Structural characterization of the Mr = 55,000 antigen (ZP3) of porcine oocyte zona pellucida. Purification and characterization of alpha- and beta-glycoproteins following digestion of lactosaminoglycan with endo-beta-galactosidase. J. Biol Chem. 262, 564–571.
46. Govind, C. K., Srivastava, N., and Gupta, S. K. (2002) Evaluation of the immunocontraceptive potential of Escherichia coli expressed recombinant non-human primate zona pellucida glyco-proteins in homologous animal model. Vaccine. 21, 78–88.
47. Govind, C. K., Hasegawa, A., Koyama, K., and Gupta, S. K. (2000) Delineation of a conserved B cell epitope on bonnet monkey (Macaca radiata) and human zona pellucida glyco-protein-B by monoclonal antibodies demonstrating inhibition of sperm-egg binding. Biol. Reprod. 62, 67–75.
48. Virant-Klun, I., Tomazevic, T., Bacer-Kermavner, L., Mivsek, J., Valentincic-Gruden, B., and Meden-Vrtovec, H. (2003) Successful freezing and thawing of blastocysts cultured in sequential media using a modified method. Fertil. Steril. 79, 1428–1433.
49. Sternberger, L. A., and Joseph, S. A. (1979) The unlabelled antibody method. Contrasting color staining of paired hormones without antibody removal. J. Histochem. Cytochem. 27, 1424–1429.
50. Hoek, A., van Kasteren, Y. , de Haan-Meulman, M., Schoemaker, J., and Drexhage, H. A. (1993) Dysfunction of monocytes and dendritic cells in patients with premature ovarian failure. Am. J. Reprod. Immunol. 30, 207–217.
51. Hoek, A., van Kasteren, Y. , de Haan-Meulman, M., Hooijkaas, H., Schoemaker, J., and Drexhage, H. A. (1995) Analysis of peripheral blood lymphocyte subsets, NK cells, and delayed type hypersensitivity skin test in patients with premature ovarian failure. Am. J. Reprod. Immunol. 33, 495–502.
52. Bousfield, G. R., Butnev, V. Y. , Gotschall, R. R., Baker, V. L., and Moore, W. T. (1996) Structural features of mammalian gonadotropins. Mol. Cell Endocrinol. 125, 3–19.
Acknowledgments
Acknowledgments We thank Drs. Bonnie S. Dunbar and Sarvamangala V. Prasad of the Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, for kindly supplying additional ZP1,2,3 antibodies and Dr. A. Neil Barclay of the Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom, who kindly provided mouse antirat Ia and LCA monoclonal antibodies. Peroxidase conjugate of swine antimouse IgG was kindly provided by Dr. Jana Peknicova of the Department of Biology and Biochemistry of Fertilization, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, and HLA-DR was kindly donated by Drs. Ivan Hilgert and Vaclav Horejsi of the Institute of Molecular Genetics, Academy of Sciences and Faculty of Sciences, Charles University, Prague, Czech Republic. Clone F15-42-01 to human Thy-1dp was kindly donated by Dr. Rosemarie Dalchau, Institute of Child Health, University of London. We also thank Drs. Helena Meden-Vrtovec, TomaĹľ TomaĹľeviÄŤ, Jasna Ĺ inkovec, and Andrej Vogler of the Department of Obstetrics and Gynecology, University of Ljubljana Medical Center, for stimulating suggestions and support, as well as excellent laparoscopic collection of OSE cells and ovarian biopsies by Dr. Andrej Vogler. This work was supported by the Physicians' Medical Education and Research Foundation award to A.B.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Humana Press, a part of Springer Science + Business Media, LLC
About this protocol
Cite this protocol
Bukovsky, A. et al. (2008). Study Origin of Germ Cells and Formation of New Primary Follicles in Adult Human and Rat Ovaries. In: Hou, S.X., Singh, S.R. (eds) Germline Stem Cells. Methods in Molecular Biology™, vol 450. Humana Press. https://doi.org/10.1007/978-1-60327-214-8_16
Download citation
DOI: https://doi.org/10.1007/978-1-60327-214-8_16
Publisher Name: Humana Press
Print ISBN: 978-1-60327-213-1
Online ISBN: 978-1-60327-214-8
eBook Packages: Springer Protocols