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Long-term impact of immunosuppressants at therapeutic doses on male reproductive system in unilateral nephrectomized
Yehui Chen1, Zhi Zhang, Yun Lin
1Department of Urology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, China. cyhly@163.com
Abstract:
Cyclosporine, tacrolimus, and sirolimus are commonly used in renal transplant recipients to prevent rejection. However, information for comparative effects of these agents on the male productive system is extremely limited and controversial. In a physiologically and clinically relevant rat model of unilateral nephrectomy, we demonstrated that long-term oral administration of both cyclosporine and sirolimus at doses equivalent to the therapeutic levels used for postrenal transplant patients significantly affects testicular development and the hypothalamic-pituitary-gonadal axis accompanied by profound histological changes of testicular structures on both light and electron microscopic examinations. Spermatogenesis was also severely impaired as indicated by low total sperm counts along with reduction of sperm motility and increase in sperm abnormality after treatment with these agents, which may lead to male infertility. On the other hand, treatment with therapeutic dose of tacrolimus only induced mild reduction of sperm count without histological evidence of testicular injury. The current study clearly demonstrates that commonly used immunosuppressants have various impacts on male reproductive system even at therapeutic levels. Our data provide useful information for the assessment of male infertility in renal transplant recipients who wish to father children. Clinical trials to address these issues should be urged.
Insights
Common immunosuppressants cyclosporine and sirolimus significantly impair male reproductive health and testicular function in rats. Tacrolimus showed milder effects, highlighting varied impacts on the male reproductive system at therapeutic levels.
Area of Science:
- Reproductive Toxicology
- Transplantation Immunology
- Endocrinology
Background:
- Cyclosporine, tacrolimus, and sirolimus are vital immunosuppressants post-renal transplant.
- Limited data exists on their comparative effects on the male reproductive system.
Purpose of the Study:
- To investigate the long-term effects of therapeutic doses of cyclosporine, sirolimus, and tacrolimus on the male reproductive system in a rat model.
Main Methods:
- Rats underwent unilateral nephrectomy and received long-term oral administration of cyclosporine, sirolimus, or tacrolimus at therapeutic equivalent doses.
- Evaluations included testicular histology (light and electron microscopy), sperm parameters (count, motility, abnormality), and assessment of the hypothalamic-pituitary-gonadal axis.
Main Results:
- Cyclosporine and sirolimus significantly impaired testicular development, induced histological damage, reduced sperm count and motility, and increased sperm abnormalities.
- Tacrolimus treatment resulted in a mild reduction in sperm count without observable testicular histological injury.
- Both cyclosporine and sirolimus affected the hypothalamic-pituitary-gonadal axis.
Conclusions:
- Commonly used immunosuppressants like cyclosporine and sirolimus have significant adverse effects on male reproductive function and testicular structure even at therapeutic levels.
- Tacrolimus appears to have a less pronounced impact on male reproductive health compared to cyclosporine and sirolimus.
- These findings are crucial for assessing male infertility risk in renal transplant recipients and warrant further clinical investigation.
