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

ObjectiveTo investigate the mechanisms responsible for the testicular abnormalities and infertility of previously generated male protein C inhibitor (PCI)-deficient mice.DesignDetermination 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.SettingAnimal research and histologic analysis.Animal(s)Male mice of desired genotype.Intervention(s)Fertility testing of double knockout mice.Main Outcome Measure(s)Infertility of PCI−/−uPA−/− and PCI−/−tPA−/− double knockout mice.Result(s)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.Conclusion(s)The abnormal spermatogenesis of PCI (plasminogen activator inhibitor-3)-deficient mice cannot be rescued by single plasminogen activator knockout.