Investigating the effects of fipronil on male fertility: Insight into the mechanism of capacitation

Fipronil (FPN) is a widely used phenylpyrazole pesticide for the control of insects and removal of veterinary pet fleas, ticks, etc. Although FPN presents moderate hazards to human health, people are readily exposed in daily life. FPN acts by impairing the central nervous systems of insects by blocking gamma-aminobutyric acid (GABA) and glutamate-activated chloride channels. A previous study demonstrated that GABA and GABA(A)R are present in spermatozoa and play various roles in the process of sperm capacitation, which is required for fertilization. However, the effects of FPN on mammalian fertility are not yet fully understood. Therefore, the present study was designed to investigate the effects of FPN on spermatozoa. Herein, we treated various concentrations of FPN (0.1, 1, 10, 100, and 300 mu M) or a control treatment with mouse spermatozoa. FPN treatment significantly reduced sperm motility, motion kinematic parameters, and intracellular ATP level, whereas the acrosome reaction was enhanced. Levels of phospho-PKA and phospho-tyrosine substrate were significantly decreased in a dose-dependent manner. Meanwhile, there was no difference between control and treatment groups in the level of GABA(A)R beta-3. Only the ratio of GABA(A)R beta-3 pS408/pS409 was significantly decreased at higher concentrations of FPN. Moreover, cleavage and blastocyst formation rates were also significantly decreased by FPN treatments. Taken together, these data suggest that FPN can directly and indirectly suppress various sperm functions. Therefore, FPN can negatively affect male fertility leading to infertility. From these results, we suggest that the use of FPN as a pesticide requires the attention of reproductive toxicity.