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.

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a b s t r a c tA sweeping sphere clipping method is presented for computing the minimum distance between two Bézier curves. The sweeping sphere is constructed by rolling a sphere with its center point along a curve. The initial radius of the sweeping sphere can be set as the minimum distance between an end point and the other curve. The nearest point on a curve must be contained in the sweeping sphere along the other curve, and all of the parts outside the sweeping sphere can be eliminated. A simple sufficient condition when the nearest point is one of the two end points of a curve is provided, which turns the curve/curve case into a point/curve case and leads to higher efficiency. Examples are shown to illustrate efficiency and robustness of the new method.

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