Department of Animal Science and Biotechnology, Kyungpook National University, Sangju, Gyeongsangbuk-do 37224, Republic of Korea.
Department of Animal Science and Biotechnology, Kyungpook National University, Sangju, Gyeongsangbuk-do 37224, Republic of Korea; Department of Animal Biotechnology, Kyungpook National University, Sangju, Gyeongsangbuk-do 37224, Republic of Korea.
Reprod Toxicol. 2020 Jun;94:1-7. doi: 10.1016/j.reprotox.2020.04.002. Epub 2020 Apr 12.
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 GABAR 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 μM) 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 GABAR β-3. Only the ratio of GABAR β-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.
氟虫腈（FPN）是一种广泛用于控制昆虫和去除兽医宠物跳蚤、蜱等的苯吡唑类农药。尽管 FPN 对人体健康有中度危害，但人们在日常生活中很容易接触到它。FPN 通过阻断γ-氨基丁酸（GABA）和谷氨酸激活的氯离子通道来损害昆虫的中枢神经系统。先前的研究表明，GABA 和 GABAR 存在于精子中，并在精子获能过程中发挥各种作用，这是受精所必需的。然而，FPN 对哺乳动物生育力的影响尚不完全清楚。因此，本研究旨在探讨 FPN 对精子的影响。在此，我们用不同浓度的 FPN（0.1、1、10、100 和 300 μM）或对照处理处理小鼠精子。FPN 处理显著降低了精子的运动能力、运动运动学参数和细胞内 ATP 水平，而顶体反应增强。磷酸化-PKA 和磷酸酪氨酸底物的水平呈剂量依赖性显著降低。同时，GABAR β-3 的水平在对照组和处理组之间没有差异。只有在较高浓度的 FPN 下，GABAR β-3 pS408/pS409 的比值才显著降低。此外，FPN 处理还显著降低了卵裂和囊胚形成率。综上所述，这些数据表明 FPN 可以直接和间接抑制各种精子功能。因此，FPN 会对男性生育能力产生负面影响，导致不孕。根据这些结果，我们建议在使用 FPN 作为农药时需要注意生殖毒性。
