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.

  • Original Research
  • Published:

Phosphodiesterase 11 (PDE11) regulation of spermatozoa physiology

Abstract

Fertilization is well correlated with sperm concentration, rate of forward motility, and percentage of live, uncapacitated ejaculated spermatozoa, which is regulated in part by cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Phosphodiesterases (PDEs) hydrolyze cyclic nucleotides to their corresponding monophosphates, thereby counterbalancing the activities of cAMP and cGMP, and PDE11 is highly expressed in the testis, prostate, and developing spermatozoa. However, a physiological role of PDE11 is not known. We generated PDE11 knockout (PDE11−/−) mice to investigate the role of PDE11 in spermatozoa physiology. Ejaculated sperm from PDE11−/− mice displayed reduced sperm concentration, rate of forward progression, and percentage of live spermatozoa. Pre-ejaculated sperm from PDE11−/− mice displayed increased premature/spontaneous capacitance. These data are consistent with human data and suggest a role for PDE11 in spermatogenesis and fertilization potential. This is the first phenotype described for the PDE11−/− mouse and the first report of a physiological role for PDE11.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Visconti PE, Kopf GS . Regulation of protein phosphorylation during sperm capacitation. Biol Reprod 1998; 59: 1–6.

    Article  CAS  PubMed  Google Scholar 

  2. Chang M . Fertilization capacity of spermatozoa deposited into the fallopian tubes. Nature 1951; 168: 697–698.

    Article  CAS  PubMed  Google Scholar 

  3. Chang M . Development of fertilizing capacity of rabbit spermatozoa in the uterus. Nature 1955; 175: 1036–1037.

    Article  CAS  PubMed  Google Scholar 

  4. Austin C . Observations on the penetration of the sperm into the mammalian egg. Austr J Sci Res 1951; 4: 581–596.

    CAS  Google Scholar 

  5. Austin C . The ‘capacitation’ of the mammalian sperm. Nature 1952; 170: 326.

    Article  CAS  PubMed  Google Scholar 

  6. Nantel F et al. Spermiogenesis deficiency and germ-cell apoptosis in CREM-mutant mice. Nature 1996; 380: 159–162.

    Article  CAS  PubMed  Google Scholar 

  7. Sinclair ML et al. Specific expression of soluble adenylyl cyclase in male germ cells. Mol Reprod Dev 2000; 56: 6–11.

    Article  CAS  PubMed  Google Scholar 

  8. Baxendale RW, Fraser LR . Evidence for multiple distinctly localized adenylyl cyclase isoforms in mammalian spermatozoa. Mol Reprod Dev 2003; 66: 181–189.

    Article  CAS  PubMed  Google Scholar 

  9. Breitbart H . Intracellular calcium regulation in sperm capacitation and acrosomal reaction. Mol Cell Endocrinol 2002; 187: 139–144.

    Article  CAS  PubMed  Google Scholar 

  10. de Lamirande E, Leclerc P, Gagnon C . Capacitation as a regulatory event that primes spermatozoa for the acrosome reaction and fertilization. Mol Hum Reprod 1997; 3: 175–194.

    Article  CAS  PubMed  Google Scholar 

  11. Soderling SH, Beavo JA . Regulation of cAMP and cGMP signaling: new phosphodiesterases and new functions. Curr Opin Cell Biol 2000; 12: 174–179.

    Article  CAS  PubMed  Google Scholar 

  12. Francis SH, Turko IV, Corbin JD . Cyclic nucleotide phosphodiesterases: relating structure and function. Prog Nucleic Acid Res Mol Biol 2001; 65: 1–52.

    CAS  PubMed  Google Scholar 

  13. Conti M, Jin SL . The molecular biology of cyclic nucleotide phosphodiesterases. Prog Nucleic Acid Res Mol Biol 1999; 63: 1–38.

    Article  CAS  PubMed  Google Scholar 

  14. Jin SL et al. Impaired growth and fertility of cAMP-specific phosphodiesterase PDE4D-deficient mice. Proc Natl Acad Sci USA 1999; 96: 11998–12003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Masciarelli S et al. Cyclic nucleotide phosphodiesterase 3A-deficient mice as a model of female infertility. J Clin Invest 2004; 114: 196–205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Fawcett L et al. Molecular cloning and characterization of a distinct human phosphodiesterase gene family: PDE11A. Proc Natl Acad Sci USA 2000; 97: 3702–3707.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Hetman JM et al. Cloning and characterization of two splice variants of human phosphodiesterase 11A. Proc Natl Acad Sci USA 2000; 97: 12891–12895.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hogan B, Beddington R, Costantini F, Lacy E . Manipulating the Mouse Embryo, A Laboratory Manual, 2nd edn. Cold Spring Harbor Press: Cold Spring Harbor, NY, USA, 1994, pp 253–290.

    Google Scholar 

  19. Stewart CL . Production of chimeras between embryonic stem cells and embryos. Methods Enzymol 1993; 225: 823–855.

    Article  CAS  PubMed  Google Scholar 

  20. Fraser LR, Harrison RA, Herod JE . Characterization of a decapacitation factor associated with epididymal mouse spermatozoa. J Reprod Fertil 1990; 89: 135–148.

    Article  CAS  PubMed  Google Scholar 

  21. Fraser LR, Adeoya-Osiguwa S . Modulation of adenylyl cyclase by FPP and adenosine involves stimulatory and inhibitory adenosine receptors and g proteins. Mol Reprod Dev 1999; 53: 459–471.

    Article  CAS  PubMed  Google Scholar 

  22. Gresser U, Gleiter CH . Erectile dysfunction: comparison of efficacy and side effects of the PDE-5 inhibitors sildenafil, vardenafil and tadalafil—review of the literature. Eur J Med Res 2002; 7: 435–446.

    CAS  PubMed  Google Scholar 

  23. Pomara G et al. Effect of acute in vivo sildenafil or tadalafil treatments on semen parameters in patients with fertility problem, a randomized, doouble-blind, crossover study. J Sex Med 2004; 2(Suppl 2): 23(PS-5–9).

    Google Scholar 

  24. Lefievre L, De Lamirande E, Gagnon C . The cyclic GMP-specific phosphodiesterase inhibitor, sildenafil, stimulates human sperm motility and capacitation but not acrosome reaction. J Androl 2000; 21: 929–937.

    CAS  PubMed  Google Scholar 

  25. Du Plessis SS, De Jongh PS, Franken DR . Effect of acute in vivo sildenafil citrate and in vitro 8-bromo-cGMP treatments on semen parameters and sperm function. Fertil Steril 2004; 81: 1026–1033.

    Article  CAS  PubMed  Google Scholar 

  26. Hellstrom WJ et al. Tadalafil has no detrimental effect on human spermatogenesis or reproductive hormones. J Urol 2003; 170: 887–891.

    Article  CAS  PubMed  Google Scholar 

  27. Weeks JL et al. High biochemical selectivity of tadalafil, sildenafil and vardenafil for human phosphodiesterase 5A1 (PDE5) over PDE11A4 suggests the absence of PDE11A4 cross-reaction in patients. Int J Impot Res 2005; 17: 5–9.

    Article  CAS  PubMed  Google Scholar 

  28. Spehr M et al. Identification of a testicular odorant receptor mediating human sperm chemotaxis. Science 2003; 299: 2054–2058.

    Article  CAS  PubMed  Google Scholar 

  29. Ren D et al. A sperm ion channel required for sperm motility and male fertility. Nature 2001; 413: 603–609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Quill TA, Ren D, Clapham DE, Garbers DL . A voltage-gated ion channel expressed specifically in spermatozoa. Proc Natl Acad Sci USA 2001; 98: 12527–12531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Carlson AE et al. CatSper1 required for evoked Ca2+ entry and control of flagellar function in sperm. Proc Natl Acad Sci USA 2003; 100: 14864–14868.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Baxendale RW, Fraser LR . Immunolocalization of multiple Galpha subunits in mammalian spermatozoa and additional evidence for Galphas. Mol Reprod Dev 2003; 65: 104–113.

    Article  CAS  PubMed  Google Scholar 

  33. Esposito G et al. Mice deficient for soluble adenylyl cyclase are infertile because of a severe sperm-motility defect. Proc Natl Acad Sci USA 2004; 101: 2993–2998.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Spehr M et al. Particulate adenylate cyclase plays a key role in human sperm olfactory receptor-mediated chemotaxis. J Biol Chem 2004; 279: 40194–40203.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to C Wayman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wayman, C., Phillips, S., Lunny, C. et al. Phosphodiesterase 11 (PDE11) regulation of spermatozoa physiology. Int J Impot Res 17, 216–223 (2005). https://doi.org/10.1038/sj.ijir.3901307

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijir.3901307

Keywords

This article is cited by

Search

Quick links