Studying nonobstructive azoospermia in cystinosis: histologic examination of testes and epididymis and sperm analysis in a Ctns−/− mouse model

ObjectiveTo study the pathogenesis of male infertility in cystinosis due to nonobstructive azoospermia, using a Ctns−/− mouse model.DesignObservational case-control study.SettingAcademic research laboratory.Animal(s)Male C57BL/6 Ctns−/− mice were compared with C57BL/6 wild-type (wt) mice.Intervention(s)None.Main Outcome Measure(s)Fertility was studied using litter size (n = 3 vs. n = 2). After animals were sacrificed, testes, epididymis, and vas deferens were removed for testicular cystine measurements (n = 5 vs. n = 6), histologic studies (n = 3 vs. n = 3), and sperm analysis (n = 3 vs. n = 3).Result(s)Mean testicular cystine content was significantly higher in Ctns−/− mice compared with wt mice (26.6 ± 1.22 vs. 0.1 ± 0.01 nmol cystine/mg protein). Testes of Ctns−/− mice had lower weight compared with wt mice (0.096 ± 0.009 g vs. 0.112 ± 0.004 g), but mice fertility was similar (litter size 6.6 ± 1.4 vs. 6.3 ± 2.6 pups). Neither histologic nor sperm abnormalities were found.Conclusion(s)The Ctns−/− mouse model generated on C57BL/6 background is not suitable for clarifying the pathogenesis of male infertility in cystinosis. The etiology of nonobstructive azoospermia in these patients remains unclear.