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


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.
Weidinger
S
S
Department of Dermatology and Allergy, Institute for Medical Statistics and Epidemiology, Technical University Munich, Germany. weidinger@lrz.tum.de
Mayerhofer
A
A
Kunz
L
L
Albrecht
M
M
Sbornik
M
M
Wunn
E
E
Hollweck
R
R
Ring
J
J
Kohn
F M
FM
D002118:Calcium / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D044464:Receptor, PAR-2 / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology; D012697:Serine Endopeptidases / Q000378:metabolism* / Q000494:pharmacology*; D013081:Sperm Motility / Q000187:drug effects* / Q000502:physiology*; D013094:Spermatozoa / Q000187:drug effects / Q000201:enzymology; D053802:Tryptases
D044464:Receptor, PAR-2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D012697:Serine Endopeptidases; D053802:Tryptases; D002118:Calcium