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Progesterone-enhanced sperm hyperactivation through IP3–PKC and PKA signals

  • Original Article
  • Published:
Reproductive Medicine and Biology

Abstract

Propose

The present study examined whether regulation of progesterone-enhanced hyperactivation of spermatozoa is associated with the production of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) by phospholipase C (PLC) and cyclic adenosine monophosphate (cAMP) by adenylate cyclase (AC), as well as activation of protein kinase C (PKC) and protein kinase A (PKA).

Methods

Hamster spermatozoa were hyperactivated by incubation for 4 h in modified Tyrode’s albumin lactate pyruvate (mTALP) medium. In order to examine the effects of IP3 receptor (IP3R), PKC and PKA on progesterone-enhanced hyperactivation, their inhibitors (xestospongin C, bisindolylmaleimide 1 and H-89) were used.

Results

Progesterone-enhanced hyperactivation was significantly suppressed by the inhibitors of IP3R, PKC and PKA.

Conclusions

The results suggest that progesterone-enhanced sperm hyperactivation occurs through two signal pathways. One is an intracellular Ca2+ signal through production of IP3 and DAG by PLC, binding of IP3 to IP3R and activation of PKC by DAG and Ca2+. The other is a cAMP–PKA signal through production of cAMP by AC and activation of PKA by cAMP.

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References

  1. Yanagimachi R. Mammalian fertilization. In: Knobil E, Neill JD (eds). The physiology of reproduction, 2nd edn. New York: Raven Press; 1994. p. 189–317.

  2. Fujinoki M. Non-genomic regulation of mammalian sperm hyperactivation. Reprod Med Biol. 2009; 8:47–52.

    Article  CAS  Google Scholar 

  3. Suarez SS, Ho HC. Hyperactivated motility in sperm. Reprod Domest Anim. 2003; 38:119–24.

    Article  PubMed  CAS  Google Scholar 

  4. Baldi E, Luconi M, Muratori M, Marchiani S, Tamburrino L, Forti G. Nongenomic activation of spermatozoa by steroid hormones: facts and fictions. Mol Cell Endocrinol. 2009; 308:39–46.

    Article  PubMed  CAS  Google Scholar 

  5. Yudine AI, Gottlieb W, Meizel S. Ultrastructural studies of the early events of the human sperm acrosome reaction as initiated by human follicular fluid. Gamete Res. 1988; 20:11–24.

    Article  Google Scholar 

  6. Noguchi T, Fujinoki M, Kitazawa M, Inaba N. Regulation of hyperactivation of hamster spermatozoa by progesterone. Reprod Med Biol. 2008; 7:63–74.

    Article  CAS  Google Scholar 

  7. Fujinoki M. Melatonin-enhanced hyperactivation of hamster sperm. Reproduction. 2008; 136:533–41.

    Article  PubMed  CAS  Google Scholar 

  8. Fujinoki M. Serotonin-enhanced hyperactivation of hamster sperm. Reproduction. 2011; 142:255–66.

    Article  PubMed  CAS  Google Scholar 

  9. Langlais J, Roberts KD. A molecular membrane model of sperm capacitation and the acrosome reaction of mammalian spermatozoa. Gamete Res. 1985; 12:183–224.

    Article  CAS  Google Scholar 

  10. Okamura N, Tajima Y, Soejima A, Masuda H, Sugita Y. Sodium bicarbonate in seminal plasma stimulates the motility of mammalian spermatozoa through direct activation of adenylate cyclase. J Biol Chem. 1985; 260:9699–705.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  12. Visconti PE, Stewart-Savage J, Blasco A, Battaglia L, Miranda P, Kopf GS, et al. Roles of bicarbonate, cAMP, and protein tyrosine phosphorylation on capacitation and the spontaneous acrosome reaction of hamster sperm. Biol Reprod. 1999; 61:76–84.

    Article  PubMed  CAS  Google Scholar 

  13. Fujinoki M, Kawamura T, Toda T, Ohtake H, Ishimoda-Takagi T, Shimizu N, et al. Identification of 36-kDa flagellar phosphoproteins associated with hamster sperm motility. J Biochem. 2003; 133:361–9.

    Article  PubMed  CAS  Google Scholar 

  14. Fujinoki M, Kawamura T, Toda T, Ohtake H, Ishimoda-Takagi T, Shimizu N, et al. Identification of 36 kDa phosphoprotein in fibrous sheath of hamster spermatozoa. Comp Biochem Physiol B: Biochem Mol Biol. 2004; 137(4):509–20.

    Article  Google Scholar 

  15. Fujinoki M, Ishimoda-Takagi T, Ohtake H. Serine/threonine phosphorylation associated with hamster sperm hyperactivation. Reprod Med Biol. 2004;3:223–30.

    Article  CAS  Google Scholar 

  16. Fujinoki M, Suzuki T, Takayama T, Shibahara H, Ohtake H. Profiling of proteins phosphorylated or dephosphorylated during hyperactivation via activation on hamster spermatozoa. Reprod Med Biol. 2006; 5:123–35.

    CAS  Google Scholar 

  17. Visconti PE, Moore GD, Bailey JL, Leclerc P, Connors SA, Pan D, et al. Capacitation of mouse spermatozoa II. Protein tyrosine phosphorylation and capacitation are regulated by a cAMP-dependent pathway. Development. 1995; 121:1139–50.

    PubMed  CAS  Google Scholar 

  18. Fujinoki M, Ohtake H, Okuno M. Tyrosine phosphorylation and dephosphorylation associated with motility of hamster spermatozoa. Biomed Res. 2001; 22:147–55.

    CAS  Google Scholar 

  19. Visconti PE, Galantino-Homer H, Moore GD, Bailey JL, Ning X, Fornes M, et al. The molecular basis of sperm capacitation. J Androl. 1998; 19:242–8.

    PubMed  CAS  Google Scholar 

  20. Ho HC, Suarez SS. An inositol 1,4,5-trisphoshate receptor-gated intracellular Ca2+ store is involved in regulating sperm hyperactivated motility. Biol Reprod. 2001; 65:1606–16.

    Article  PubMed  CAS  Google Scholar 

  21. Breitbart H. Intracellular calcium regulation in sperm capacitation and acrosomal reaction. Mol Cell Endocrinol. 2002; 187:139–44.

    Article  PubMed  CAS  Google Scholar 

  22. Ho HC, Granish KA, Suarez SS. Hyperactivated motility of bull sperm is triggered at the axoneme by Ca2+ and not cAMP. Dev Biol. 2002; 250:208–17.

    Article  PubMed  CAS  Google Scholar 

  23. Marín-Briggiler CI, Jha KN, Chertihin O, Buffone MG, Herr JC, Vazquez-Levin MH, et al. Evidence of the presence of calcium/calmodulin-dependent protein kinase IV in human sperm and its involvement in motility regulation. J Cell Sci. 2005; 118:2013–22.

    Article  PubMed  Google Scholar 

  24. Sueldo CE, Alexander NJ, Oehninger S, Burkman LJ, Subias E, Acosta AA, et al. Effect of progesterone on human zona pellucida sperm binding and oocyte penetrating capacity. Fertil Steril. 1993; 60:137–40.

    PubMed  CAS  Google Scholar 

  25. Yang J, Serres C, Philibert D, Robel P, Baulieu EE, Jouannet P. Progesterone and RU486: opposing effects on human sperm. Proc Natl Acad Sci USA. 1994; 91:529–33.

    Article  PubMed  CAS  Google Scholar 

  26. du Plessis SS, Hagenaar K, Lampiao F. The in vitro effects of melatonin on human sperm function and its scavenging activities on NO and ROS. Andrologia. 2010; 42:112–6.

    Article  PubMed  Google Scholar 

  27. Fujinoki M. Suppression of progesterone enhanced hyperactivation in hamster spermatozoa by estrogen. Reproduction. 2010; 140:453–64.

    Article  PubMed  CAS  Google Scholar 

  28. Lösel R, Wehling M. Nongenomic actions of steroid hormones. Nature Rev Mol Cell Biol. 2003; 4:6–56.

    Article  Google Scholar 

  29. Luconi M, Francavilla F, Porazzi I, Macerola B, Forti G, Baldi E. Human spermatozoa as a model for studying membrane receptors mediating rapid nongenomic effects of progesterone and estrogens. Steroids. 2004; 69:553–9.

    Article  PubMed  CAS  Google Scholar 

  30. Ho HC, Suarez SS. Hyperactivation of mammalian spermatozoa: function and regulation. Reproduction. 2001; 122:519–26.

    Article  PubMed  CAS  Google Scholar 

  31. Ho HC, Suarez SS. Characterization of the intracellular calcium store at the base of the sperm flagellum that regulates hyperactivated motility. Biol Reprod. 2003; 68:1590–6.

    Article  PubMed  CAS  Google Scholar 

  32. Ignotz GG, Suarez SS. Calcium/calmodulin and calmodulin kinase II stimulate hyperactivation in demembranated bovine sperm. Biol Reprod. 2005; 73:519–26.

    Article  PubMed  CAS  Google Scholar 

  33. Strünker T, Goodwin N, Brenker C, Kashikar ND, Weyand I, Seifert R, et al. The CatSper channel mediates progesterone-induced Ca2+ influx in human sperm. Nature. 2011; 471:382–6.

    Article  PubMed  Google Scholar 

  34. Lishko PV, Botchkina IL, Kirichok Y. Progesterone activates the principal Ca2+ channel of human sperm. Nature. 2011; 471:387–91.

    Article  PubMed  CAS  Google Scholar 

  35. Harrison DA, Carr DW, Meizel S. Involvement of protein kinase A and A kinase anchoring protein in the progesterone-initiated human sperm acrosome reaction. Biol Reprod. 2000; 62:811–20.

    Article  PubMed  CAS  Google Scholar 

  36. Gellersen B, Fernandes MS, Brosens JJ. Non-genomic progesterone actions in female reproduction. Hum Reprod Update. 2009; 15:119–38.

    Article  PubMed  CAS  Google Scholar 

  37. Teves ME, Guidobaldi HA, Uñates DR, Sanchez R, Miska W, Publicover SJ, et al. Molecular mechanism for human sperm chemotaxis mediated by progesterone. PLoS ONE. 2009; 4:e8211.

    Article  PubMed  Google Scholar 

  38. Fujinoki M, Ohtake H, Okuno M. Serine phosphorylation of flagellar proteins associated with the motility activation of hamster spermatozoa. Biomed Res. 2001; 22:45–58.

    CAS  Google Scholar 

  39. de Lamirande E, O’Flaherty C. Sperm activation: role of reactive oxygen species and kinases. Biochim Biophys Acta. 2008; 1784:106–15.

    Article  PubMed  Google Scholar 

  40. Carrera A, Moos J, Ning XP, Gerton GL, Tesarik J, Kopf GS, et al. Regulation of protein tyrosine phosphorylation in human sperm by a calcium/calmodulin-dependent mechanism: identification of A kinase anchoring proteins as major substrates for tyrosine phosphorylation. Dev Biol. 1996; 180:284–96.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was partially supported by a Grants-in-Aid for Young Scientists (B) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (no. 15790860 and no. 18791135).

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Authors and Affiliations

  1. Department of Physiology, School of Medicine, Dokkyo Medical University, Mibu, Tochigi, 321-0293, Japan

    Masakatsu Fujinoki

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  1. Masakatsu Fujinoki
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Correspondence to Masakatsu Fujinoki.

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Fujinoki, M. Progesterone-enhanced sperm hyperactivation through IP3–PKC and PKA signals. Reprod Med Biol 12, 27–33 (2013). https://doi.org/10.1007/s12522-012-0137-6

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  • DOI: https://doi.org/10.1007/s12522-012-0137-6

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