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

OBJECTIVE: 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. SETTING: SUNY Upstate Medical University, Syracuse, NY. PATIENT(S): Men (n = 12) visited the Andrology Department for fertility evaluation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sperm respiration. RESULT(S): 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. CONCLUSION(S): 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.

Cannabinoids inhibit the respiration of human sperm.

OBJECTIVE: To investigate the effects of the psychotropic compounds Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and Delta(8)-tetrahydrocannabinol (Delta(8)-THC) on sperm mitochondrial O(2) consumption (respiration). SETTING: State University of New York Upstate Medical University, Syracuse, New York. PATIENT(S): Forty-one men who visited the andrology laboratory for fertility evaluation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): A phosphorescence analyzer that measures O(2) concentration in sperm suspensions as a function of time was used to measure respiration. RESULT(S): An immediate decline in the rate of respiration was observed when Delta(9)-THC or Delta(8)-THC was added to washed sperm. The inhibition was concentration dependent, and Delta(9)-THC was the more potent of the two compounds. Respiration was much less affected when Delta(9)-THC or Delta(8)-THC was added to neat semen, suggesting the presence of protective factors in seminal plasma. Both compounds inhibited the respiration of isolated mitochondria, illustrating that direct mitochondrial damage is likely the primary mechanism of action. CONCLUSION(S): The two main active cannabinoids of the marijuana plant, Delta(9)- and Delta(8)-THC, are potent inhibitors of mitochondrial O(2) consumption in human sperm. These findings emphasize the adverse effects of these toxins on male fertility. The cytoprotective capacity of seminal plasma deserves further investigation.