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Female infertility in mice lacking connexin 37

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Abstract

The signals regulating ovarian follicle development and the mechanisms by which they are communicated are largely undefined1. At birth, the ovary contains primordial follicles consisting of meiotically arrested oocytes surrounded by a single layer of supporting (granulosa) cells. Periodically, subsets of primordial follicles undergo further development during which the oocyte increases in size and the granulosa cells proliferate, stratify and develop a fluid-filled antrum. After ovulation, oocytes resume meiosis and granulosa cells retained in the follicle differentiate into steroidogenic cells, forming the corpus luteum1,2. It has been proposed that intercellular signalling through gap junction channels may influence aspects of follicular development3,4. Gap junctions are aggregations of intercellular channels composed of connexins, a family of at least 13 related proteins that directly connect adjacent cells allowing the diffusional movement of ions, metabolites, and other potential signalling molecules5. Here we show that connexin 37 is present in gap junctions between oocyte and granulosa cells and that connexin-37-deficient mice lack mature (Graafian) follicles, fail to ovulate and develop numerous inappropriate corpora lutea. In addition, oocyte development arrests before meiotic competence is achieved. Thus, cell–cell signalling through intercellular channels critically regulates the highly coordinated set of cellular interactions required for successful oogenesis and ovulation.

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References

  1. Eppig, J. J. Bioessays 13, 569–574 (1991).

    Article  CAS  Google Scholar 

  2. Wassermann, P. M. & Albertini, D. F. in The Physiology of Reproduction (eds Knobil, E. & Neill, J. D.) 79–122 (Raven, New York, 1994).

    Google Scholar 

  3. Anderson, E. & Albertini, D. F. J. Cell Biol. 71, 680–686 (1976).

    Article  CAS  Google Scholar 

  4. Gilula, N. B., Epstein, M. L. & Beers, W. H. J. Cell Biol. 78, 58–75 (1978).

    Article  CAS  Google Scholar 

  5. Goodenough, D. A., Goliger, J. A. & Paul, D. L. Annu. Rev. Biochem. 65, 475–502 (1996).

    Article  CAS  Google Scholar 

  6. Beyer, E. C., Kistler, J., Paul, D. L. & Goodenough, D. A. J. Cell Biol. 108, 596–605 (1989).

    Article  Google Scholar 

  7. Haefliger, J. A. et al. J. Biol. Chem. 267, 2057–2064 (1992).

    CAS  PubMed  Google Scholar 

  8. Reed, K. E. et al. J. Clin Invest. 91, 997–1004 (1993).

    Article  CAS  Google Scholar 

  9. Goliger, J. A. & Paul, D. L. Dev. Dyn. 200, 1–13 (1994).

    Article  CAS  Google Scholar 

  10. Valdimarsson, G., De Sousa, P. A. & Kidder, G. M. Mol. Reprod. Dev. 36, 7–15 (1993).

    Article  CAS  Google Scholar 

  11. Bjorkman, N. Acta Anat. 51, 125–147 (1962).

    Article  CAS  Google Scholar 

  12. El-Fouly, M. A., Cook, B., Nekola, M. & Nalbandov, A. V. Endocrinology 87, 286–293 (1970).

    Article  CAS  Google Scholar 

  13. Sorensen, R. A. & Wassarman, P. M. Dev. Biol. 50, 531–536 (1976).

    Article  CAS  Google Scholar 

  14. Mattson, B. A. & Albertini, D. F. Mol. Reprod. Dev. 25, 374–383 (1990).

    Article  CAS  Google Scholar 

  15. Cho, W. K., Stern, S. & Biggers, J. D. J. Exp. Zool. 187, 383–386 (1974).

    Article  CAS  Google Scholar 

  16. Dekel, N. & Beers, W. H. Proc. Natl Acad. Sci. USA 75, 4369–4373 (1978).

    Article  ADS  CAS  Google Scholar 

  17. Bornslaeger, E. A. & Schultz, R. M. Biol. Reprod. 33, 698–704 (1985).

    Article  CAS  Google Scholar 

  18. Bergoffen, J. et al. Science 262, 2039–2042 (1993).

    Article  ADS  CAS  Google Scholar 

  19. Britz-Cunningham, S. H., Shah, M. M., Zuppan, C. W. & Fletcher, W. H. N. Engl. J. Med. 332, 1323–1329 (1995).

    Article  CAS  Google Scholar 

  20. Reaume, A. G. et al. Science 267, 1831–1834 (1995).

    Article  ADS  CAS  Google Scholar 

  21. Nelson, L. M. et al. J. Clin. Endocrinol. Metab. 79, 1470–1475 (1994).

    CAS  PubMed  Google Scholar 

  22. Tybulewicz, V. L., Crawford, C. E., Jackson, P. K., Bronson, R. T. & Mulligan, R. C. Cell 65, 1153–1163 (1991).

    Article  CAS  Google Scholar 

  23. Li, E., Bestor, T. H. & Jaenisch, R. Cell 69, 915–926 (1992).

    Article  CAS  Google Scholar 

  24. Willecke, K. et al. J. Cell Biol. 114, 1049–1057 (1991).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Alexander M. Simon & David L. Paul

  2. Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Alexander M. Simon & David L. Paul

  3. Cardiovascular Research Center, Mass General Hospital East, Charlestown, Massachusetts, 02129, USA

    En Li

Authors
  1. Alexander M. Simon
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  2. Daniel A. Goodenough
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  3. En Li
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  4. David L. Paul
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Simon, A., Goodenough, D., Li, E. et al. Female infertility in mice lacking connexin 37. Nature 385, 525–529 (1997). https://doi.org/10.1038/385525a0

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  • DOI: https://doi.org/10.1038/385525a0

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