Long-Term Effects of Conversion From Cyclosporine to Rapamycin on Testicular Function and Morphology in a Rat Transplantation Model

Abstract

PurposeThe purpose of this study was to investigate the long-term effects of conversion from cyclosporine (CsA) to rapamycin on testicular function and morphology in a rat transplantation model compared with the continuous administration of CsA. MethodsFisher 344 kidneys were orthotopically transplanted into Lewis recipients. Four Fisher 344 to Lewis allograft groups were treated posttransplantation as follows: Group 1, CsA treatment to week 8 followed by rapamycin from week 8–24; Group 2, CsA from transplantation to week 24; Group 3, CsA from transplantation to week 8 then vehicle from weeks 8–24, and Group 4, control vehicle from transplantation to week 24. A fifth group (Group 5) underwent syngeneic isografts (Lewis to Lewis) with no drug treatment. At 24 week, we measured serum creatinine and sex hormones and harvested the right testis for histological analysis. ResultsAll rats showed normal serum creatinine levels. Testosterone was significantly lower in Group 1 versus Group 5 (0.85 ± 0.09 vs 1.05 ± 0.17 ng/mL; P = .008). Groups 2, 3 and 4 displayed higher testosterone values than Group 1 but lower than Group 5. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were also higher in Group 1 versus the other groups, but the differences were not significant. The histological damage score was significantly higher in Groups 1, 2, 3, and 4 versus Group 5 (1.8 ± 0.8), but the highest one was observed in Group 1 (8.3 ± 1.6). Electron microscopy showed more severe testicular ultrastructural damage in Group 1. ConclusionConversion from CsA to rapamycin resulted in more severe damage to testicular function and structure than the continuous use of CsA in a rat kidney transplantation model.