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Hum. Reprod. Advance Access published online on December 2, 2004
Human Reproduction, doi:10.1093/humrep/deh618
© 2004 by European Society of Human Reproduction and Embryology
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Received June 28, 2004
Revised September 23, 2004
Accepted October 22, 2004

Article

Tryptase inhibits motility of human spermatozoa mainly by activation of the mitogen-activated protein kinase pathway

S. Weidinger 1*, A. Mayerhofer 2, L. Kunz 2, M. Albrecht 2, M. Sbornik 1, E. Wunn 1, R. Hollweck 3, J. Ring 1, and F.M. Kohn 1

1 Department of Dermatology and Allergy, University Munich, Germany
2 Department of Anatomy, University of Munich, Germany
3 Institute for Medical Statistics and Epidemiology, Technical University Munich, Germany

* To whom correspondence should be addressed.
S. Weidinger, E-mail: weidinger{at}lrz.tum.de


  Abstract

BACKGROUND: We previously localized protease-activated receptor 2 (PAR-2) on human spermatozoa and demonstrated that activation of PAR-2 by the mast cell (MC) product tryptase inhibits sperm motility. Importantly, tryptase-secreting MCs are encountered in the male and female genital tract, implying that MC-spermatozoa interactions may be as yet unrecognized factors affecting sperm fertilizing ability. In order to elucidate how tryptase via activation of PAR-2 acts in human spermatozoa, we studied intracellular signal transduction events. METHODS AND RESULTS: Impairment of sperm motility by tryptase was not dependent on the presence of extracellular Ca2+ and tryptase did not alter intracellular Ca2+ levels. Pre-incubation with pertussis toxin (PTX) failed to prevent tryptase effects on sperm motility. Western blot analyses revealed that tryptase increased phosphorylation of the mitogen-activated protein kinases (MAPK) ERK1/2, an effect which was blocked by the MAPK pathway inhibitor PD98059. Pre-treatment of spermatozoa with this inhibitor also blocked the inhibtion of sperm motility evoked by tryptase. CONCLUSIONS: These results indicate that tryptase acts via the ERK1/2 pathway to inhibit motility of human spermatozoa.

Keywords: ERK1; 2; human spermatozoa; mast cell; motility; PAR-2; tryptase.
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