Studying non-obstructive azoospermia in cystinosis: histological examination of testes and epididymis and sperm analysis in a Ctns-/- mouse model

Objective: To investigate the pathogenesis of male infertility in cystinosis, due to non-obstructive azoospermia of unknown etiology, we used a Ctns-/- mouse model with a renal phenotype comparable to cystinosis patients to study mice fertility, histology of testes and epididymis and sperm parameters.

Design: Male C57BL/6 Ctns-/- mice were compared to C57BL/6 wild type (wt) mice. Fertility was studied using litter size. After animals were sacrificed, testes, epididymis and vasa deferens were removed for histological studies (n=3 vs n=3), sperm analysis (n=3 vs n=3) and testicular cystine measurements (n=5 vs n=6).

Results: Testes of Ctns-/- mice had lower weight compared to wt mice (0.096 + 0.009 vs 0.112 + 004 grams, p=0.05), but mice fertility was similar (litter size 6.6 + 1.4 vs 6.3 + 2.6 pups). Neither histological nor sperm abnormalities were found. Mean testicular cystine content was significantly higher in Ctns-/- mice compared to wt mice (26.6 + 1.2 vs 0.1 + 0.0 nmol cystine/mg protein, p
Conclusions: The Ctns-/- mouse model generated on C57BL/6 background is not suitable for clarifying the pathogenesis of male infertility in cystinosis. The etiology of non-obstructive azoospermia in these patients remains unclear.