Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

The meiotic checkpoint monitoring sypapsis eliminates spermatocytes via p53-independent apoptosis

Nature Genetics volume 18, pages 257–261 (1998)Cite this article

Abstract

Evidence is accumulating that meiosis is subject to ‘checkpoints’ that monitor the quality of this complex process. In yeast unresolved double strand breaks (DSBs) in DNA are thought to trigger a ‘recombination checkpoint’ that leads to pachytene arrest1. In higher eukaryotes, there is evidence for a checkpoint that monitors chromosome synapsis and in mammals the most compelling evidence relates to the sex chromosomes2. In normal male mice, there is synapsis between the X and Y pseudoautosomal regions; in XSxraO mice, with a single asynaptic sex chromosome, there is arrest at the first meiotic metaphase3, the arrested cells being eliminated by apoptosis (our unpublished data). Satisfying the requirement for pseudoautosomal synapsis by providing a pairing partner for the XSxra chromosome avoids this arrest4. We have considered that this ‘synapsis checkpoint’ may be a modification of the yeast ‘recombination checkpoint’, with unresolved DSBs (a corollary of asynapsis) providing the trigger for apoptosis. DSBs induced by irradiation are known to trigger apoptosis in a number of cell types via a p53-dependent pathway5,6, and we now show that irradiation-induced spermatogonial apoptosis is also p53-dependent. In contrast, the apoptotic elimination of spermatocytes with synaptic errors proved to be p53-independent.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Roeder, G.S. Meiotic chromosomes: it takes two to tango. Genes Dev. 11, 2600–2621 (1997).

    Article  CAS  Google Scholar 

  2. Burgoyne, P.S. & Mahadevaiah, S.K. Unpaired sex chromosomes and gametogenic failure. Chromosomes Today 11, 243–263 (1993).

    Article  CAS  Google Scholar 

  3. Sutcliffe, M.J., Darling, S.M. & Burgoyne, P.S. Spermatogenesis in XY, XYSxra and XOSxra mice: a quantitative analysis of spermatogenesis throughout puberty. Mol. Reprod. Dev. 30, 81–89 (1991).

    Article  CAS  Google Scholar 

  4. Burgoyne, P.S., Mahadevaiah, S.K., Sutcliffe, M.J. & Palmer, S.J. Fertility in mice requires X-Y pairing and a Y-chromosomal ‘spermiogenesis’ gene mapping to the long arm. Cell 71, 391–398 (1992).

    Article  CAS  Google Scholar 

  5. Clarke, A.R. et al. Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature 362, 849–852 (1993).

    Article  CAS  Google Scholar 

  6. Clarke, A.R., Gledhill, S., Hooper, M.L., Bird, C.C. & Wyllie, A.H. p53 dependence of early apoptotic and proliferative responses within the mouse intestinal epithelium following-γ-irradiation. Oncogene 9, 1767–1773 (1994).

    CAS  Google Scholar 

  7. Eicher, E.M. et al. The mouse Y* chromosome involves a complex rearrangement, including interstitial positioning of the pseudoautosomal region. Cytogenet. Cell. Genet. 57, 221–230 (1991).

    Article  CAS  Google Scholar 

  8. Ford, C.E. & Evans, E.P. A reciprocal translocation in the mouse between the X chromosome and a short autosome. Cytogenetics 3, 295–305 (1964).

    Article  CAS  Google Scholar 

  9. Reader, C.R. & Solari, A.J. The histology and cytology of the seminiferous epithelium of mice carrying Searle's X-autosome translocation. Acta Physiol. Lat. Am. 19, 249–256 (1969).

    CAS  PubMed  Google Scholar 

  10. Burgoyne, P.S. & Baker, T.G. Meiotic pairing and gametogenic failure. In Controlling events in Meiosis, 38th Symposium of the Society for Experimental Biology (eds Evans, C.W. & Dickinson, H.G.) 349–362 (The Company of Biologists Ltd, Cambridge, 1984).

    Google Scholar 

  11. Barlow, C., Brown, K.D., Deng, C.-X., Tagle, D.A. & Wynshaw-Boris, A. Atm selectively regulates distinct p53-dependent cell-cycle checkpoint and apoptotic pathways. Nature Genet. 17, 453–456 (1997).

    Article  CAS  Google Scholar 

  12. Allan, D.J., Harmon, B.V. & Kerr, J.F.R. Cell death in spermatogenesis. In Perspectives on mammalian cell death (ed. Potten, C.S.) 229–258 (Oxford University Press, London, 1987).

    Google Scholar 

  13. Beumer, T.L., Roepers-Gajadien, H.L., Gademan, I.S., Rutgers, D.H. & de Rooij, D.G. p21(Cip1/WAF1) expression in the mouse testis before and after X irradiation. Mol. Reprod. Dev. 47, 240–247 (1997).

    Article  CAS  Google Scholar 

  14. Hendry, J.H., Adeeko, A., Potten, C.S. & Morris, I.D. P53 deficiecny produces fewer regenerating spermatogenic tubules after irradiation. Int. J. Radiat. Biol. 70, 677–682 (1996).

    Article  CAS  Google Scholar 

  15. Schwartz, D., Goldfinger, N. & Rotter, V. Expression of the p53 protein in spermatogenesis is confined to the tetraploid pachytene primary spermatocytes. Oncogene 8, 1487–1494 (1993).

    CAS  PubMed  Google Scholar 

  16. Rotter, V. et al. Mice with reduced levels of p53 protein exhibit the testicular giant-cell degenerative syndrome. Proc. Natl. Acad. Sci. USA 90, 9075–9079 (1993).

    Article  CAS  Google Scholar 

  17. Donehower, L.A. et al. Mice deficient in p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356, 215–221 (1992).

    Article  CAS  Google Scholar 

  18. Xu, L., Weiner, B.M. & Kleckner, N. Meiotic cells monitor the status of the interhomolog recombination complex. Genes Dev. 11,106–118 (1997).

    Article  CAS  Google Scholar 

  19. Edelmann, W. et al. Meiotic pachytene arrest in MLH1-deficient mice. Cell 85, 1125–1134 (1996).

    Article  CAS  Google Scholar 

  20. Xu, Y. et al. Targeted disruption of ATM leads to growth retardation, chromosomal fragmentation during meiosis, immune defects, and thymic lymphoma. Genes Dev. 10, 2411–2422 (1996).

    Article  CAS  Google Scholar 

  21. Plug, A.W. et al. ATM and RPA in meiotic chromosome synapsis and recombination. Nature Genet. 17, 457–461 (1997).

    Article  CAS  Google Scholar 

  22. Barlow, C., Liyanage, M., Moens, P.B., Deng, C.-X., Ried, T. & Wynshaw-Boris, A. Partial rescue of prophase I defects of Atm-deficient mice by p53 and p21 null alleles. Nature Genet. 17, 462–466 (1997).

    Article  CAS  Google Scholar 

  23. Miklos, G.L.G. Sex chromosome pairing and male fertility. Cytogenet. Cell. Genet. 13, 558–577 (1974).

    Article  CAS  Google Scholar 

  24. Li, X. & Nicklas, R.B. Mitotic forces control a cell-cycle checkpoint. Nature 373, 630–632 (1995).

    Article  CAS  Google Scholar 

  25. Evans, E.P. & Phillips, R.J. Inversion heterozygosity and the origin of XO daughters of Bpal+ female mice. Nature 256, 40–41 (1975).

    Article  CAS  Google Scholar 

  26. Evans, E.P., Breckon, G. & Ford, C.E. An air-drying method for meiotic preparations from mammalian testes. Cytogenetics 3, 289–294 (1964).

    Article  CAS  Google Scholar 

  27. Mahadevaiah, S.K. & Mittwoch, U. Synaptonemal complex analysis in spermatocytes and oocytes of tertiary trisomic Ts(512)31H with male sterility. Cytogenet. Cell. Genet. 41, 169–176 (1986).

    Article  CAS  Google Scholar 

  28. Wijsman, J.H. et al. A new method to detect apoptosis in paraffin sections: in situ end-labeling of fragmented DNA. J. Histochem. Cytochem. 41, 7–12 (1993).

    Article  CAS  Google Scholar 

  29. Rösl, F. A simple and rapid method for detection of apoptosis in human cells. Nucleic Acids Res. 20, 5243 (1992).

    Article  Google Scholar 

  30. Abrams, J.M., White, K., Fessler, L.I. & Steller, H. Programmed cell death during Drosophila embryogenesis. Development 117, 29–43 (1993).

    CAS  Google Scholar 

  31. Henriksén, K., Kulmala, J., Toppari, J., Mehrotra, K. & Parvinen, M. Stage-specific apoptosis in the rat seminiferous epthelium: quantification of irradiation effects. J. Androl. 17, 939–943 (1996).

    Google Scholar 

Download references

Author information

Author notes

  1. Teresa Odorisio

    Present address: Laboratorio di Biologia Molecolare e Cellulare, Istituto Dermopatico dell'Immacolata, Via dei Monti di Creta 104, 00167, Roma, Italy

Authors and Affiliations

  1. Laboratory of Developmental Genetics, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK

    Teresa Odorisio, Tristan A. Rodriguez & Paul S. Burgoyne

  2. MRC Mammalian Genetics Unit, Harwell, Didcot, OX11 ORD, UK

    Edward P. Evans

  3. Department of Pathology, University Medical School, Teviot Place, Edinburgh, EH8 9AG, UK

    Alan R. Clarke

Authors
  1. Teresa Odorisio
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tristan A. Rodriguez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Edward P. Evans
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alan R. Clarke
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paul S. Burgoyne
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul S. Burgoyne.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Odorisio, T., Rodriguez, T., Evans, E. et al. The meiotic checkpoint monitoring sypapsis eliminates spermatocytes via p53-independent apoptosis. Nat Genet 18, 257–261 (1998). https://doi.org/10.1038/ng0398-257

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0398-257

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing