Inhibition of human sperm respiration by 4-hydroperoxycyclophosphamide and protection by mesna and WR-1065.

Zaki S Badawy, Abdul-Kader Souid

Department of Pediatrics, State University of New York, Upstate Medical University, Syracuse, New York 13210, USA.

Fertility and sterility 2009 Jan

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To determine the effect of 4-hydroperoxycyclophosphamide (4OOH-CP) on the respiration of human sperm, and investigate the protective properties of mesna and WR-1065. SUNY Upstate Medical University, Syracuse, NY. Men (n = 12) visited the Andrology Department for fertility evaluation. None. Sperm respiration. Immediate decline in the rate of respiration was observed when 4OOH-CP was added to washed sperm or semen. The inhibition was concentration dependent. The respiration was less affected when 4OOH-CP was added to semen, suggesting the presence of protective factors in the seminal plasma. Excess of mesna or WR-1065 ameliorated the effect of 4OOH-CP. Mesna was the more potent of the two compounds. 4OOH-CP also inhibited the respiration of mitochondria from beef heart. These findings emphasize the adverse effects of alkylating agents on sperm function. The results also provide a framework for thiol drug administration with high-dose alkylating agents to protect male fertility. The protective capacity of seminal plasma deserves further testing.

Citation

Zaki S Badawy, Abdul-Kader Souid. Inhibition of human sperm respiration by 4-hydroperoxycyclophosphamide and protection by mesna and WR-1065. Fertility and sterility. 2009 Jan;91(1):173-8