Trifluoperazine effect on human sperm: The accumulation of reactive oxygen species and the decrease in the mitochondrial membrane potential

A strong link between antipsychotic drug use and reduced human sperm quality has been reported. Trifluoperazine (TFP), a commonly used antipsychotic, is now being explored for anticancer applications. Although there are hints that TFP might affect the male reproductive system, its impact on human sperm quality remains uncertain. Using a human sperm and TFP in vitro coculture system, we examined the effect of TFP (12.5, 25, 50 and 100 μM) on human sperm function and physiological parameters. The results showed that 50 μM and 100 μM TFP induced the accumulation of reactive oxygen species (ROS) and a decrease in the mitochondrial membrane potential (MMP) of human sperm, leading to decreased sperm viability, while 25 μM TFP inhibited only the penetration ability, total sperm motility, and progressive motility. Although 12.5 μM and 25 μM TFP increased [Ca²⁺]_i in human sperm, they did not affect capacitation or the acrosome reaction. These results may be explained by the observation that 12.5 μM and 25 μM TFP did not increase tyrosine phosphorylation in human sperm, although TFP increased [Ca²⁺]_i in a time-course traces similar to that of progesterone. Our results indicated that TFP could cause male reproductive toxicity by inducing the accumulation of ROS and a decrease in the MMP in human sperm.