Protease activated receptor 2 and epidermal growth factor receptor are involved in the regulation of human sperm motility.
OBJECTIVE
To investigate mechanisms of tryptase-induced reduction of sperm motility and explore whether epidermal growth factor receptor (EGF-R) and protease activated receptor 2 (PAR-2)- associated pathways are involved.


METHODS
Fresh semen was collected from healthy donors (n = 15). Semen parameters and quality were assessed in accordance with the World Health Organization (WHO) criteria. Swim-up sperm were fixed and subjected to immunocytochemistry and immunoelectronmicroscopy with specific antibodies directed against PAR-2 and EGF-R. Protein extractions from swim-up spermatozoa were analyzed by Western blotting with antibodies for both receptors. Motility of spermatozoa was evaluated by computer-assisted semen analysis.


RESULTS
Immunocytochemistry found PAR-2 and EGF-R in approximately 30% of examined human ejaculated spermatozoa. Both receptors were localized in the plasma membrane. Like tryptase, the PAR-2 synthetic agonist SLIGKV reduced sperm motility, and this effect was inhibited by application of two specific EGF-R pathway blockers (AG1478 and PD168393).


CONCLUSIONS
The observed reduction of sperm motility by tryptase through the PAR-2 receptor involves EGF-R pathways.
Zitta
Karina
K
Department of Dermatology and Allergy, Technical University Munich, Biedersteiner Strasse 29, Munich, Germany. K.Zitta@gen.vetmed.uni-muenchen.de
Albrecht
Martin
M
Weidinger
Stephan
S
Mayerhofer
Artur
A
Köhn
Frank
F
D004542:Ejaculation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D016253:Microscopy, Immunoelectron; D009842:Oligopeptides / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D044464:Receptor, PAR-2 / Q000502:physiology*; D012016:Reference Values; D012661:Semen / Q000502:physiology*; D013081:Sperm Motility / Q000187:drug effects / Q000502:physiology*; D013094:Spermatozoa / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D020032:Tyrphostins / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009842:Oligopeptides; C509204:PD168393; D011799:Quinazolines; D044464:Receptor, PAR-2; D020032:Tyrphostins; C109968:seryl-leucyl-isoleucyl--glycyl-lysyl-valine; C101044:RTKI cpd; D066246:ErbB Receptors