Male fertility and protein C inhibitor/plasminogen activator inhibitor-3 (PCI): localization of PCI in mouse testis and failure of single plasminogen activator knockout to restore spermatogenesis in PCI-deficient mice.
OBJECTIVE
To investigate the mechanisms responsible for the testicular abnormalities and infertility of previously generated male protein C inhibitor (PCI)-deficient mice.


METHODS
Determination of the localization of PCI in the reproductive organs of wild-type males. Generation of double knockout mice lacking the protease inhibitor PCI and one plasminogen activator, either urokinase (uPA) or tissue plasminogen activator (tPA), both of which are PCI-target proteases.


METHODS
Animal research and histologic analysis.


METHODS
Male mice of desired genotype.


METHODS
Fertility testing of double knockout mice.


METHODS
Infertility of PCI(-/-)uPA(-/-) and PCI(-/-)tPA(-/-) double knockout mice.


RESULTS
In the testes of wild-type males PCI was detected in spermatocytes of prophase I, as well as in late spermatids and mature spermatozoa, but absent from somatic cells. All PCI(-/-) uPA(-/-) and PCI(-/-) tPA(-/-) male mice were infertile and histologic analysis of testis showed similar alterations as previously described for PCI(-/-) mice.


CONCLUSIONS
The abnormal spermatogenesis of PCI (plasminogen activator inhibitor-3)-deficient mice cannot be rescued by single plasminogen activator knockout.
Uhrin
Pavel
P
Department of Vascular Biology and Thrombosis Research, Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria.
Schöfer
Christian
C
Zaujec
Jan
J
Ryban
Lubos
L
Hilpert
Mario
M
Weipoltshammer
Klara
K
Jerabek
Ingrid
I
Pirtzkall
Irene
I
Furtmüller
Margareta
M
Dewerchin
Mieke
M
Binder
Bernd R
BR
Geiger
Margarethe
M
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D005260:Female; D005298:Fertility / Q000235:genetics; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018046:Protein C Inhibitor / Q000032:analysis* / Q000172:deficiency / Q000235:genetics*; D013091:Spermatogenesis / Q000235:genetics; D013737:Testis / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism
D018046:Protein C Inhibitor