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BioMed Research International
Volume 2013 (2013), Article ID 690382, 9 pages
http://dx.doi.org/10.1155/2013/690382
Research Article

Long-Term Impact of Immunosuppressants at Therapeutic Doses on Male Reproductive System in Unilateral Nephrectomized Rats: A Comparative Study

1Department of Urology, Guangzhou First People’s Hospital, Guangzhou Medical University, 1 Panfu Road, Guangzhou, Guangdong 510180, China
2Reproductive Center, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, Guangdong 510080, China
3Department of Organ Transplantation, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China
4Laboratory of Electron Microscope, Southern Medical University, Guangzhou, Guangdong 510450, China
5Department of Laboratory Medicine, Guangzhou First People’s Hospital, Guangzhou Medical University, 1 Panfu Road, Guangzhou, Guangdong 510180, China
6Department of Pathology, Guangzhou First People’s Hospital, Guangzhou Medical University, 1 Panfu Road, Guangzhou, Guangdong 510180, China
7Department of Pharmacy, Guangzhou First People’s Hospital, Guangzhou Medical University, 1 Panfu Road, Guangzhou, Guangdong 510180, China
8Division of Nephrology, Department of Medicine, VA Loma Linda Healthcare System and Loma Linda University, VA Loma Linda Healthcare System (111N), 11201 Benton Street, Loma Linda, CA 92357, USA

Received 19 April 2013; Revised 20 June 2013; Accepted 20 June 2013

Academic Editor: Rodomiro Ortiz

Copyright © 2013 Yehui Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.