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Investigating the effects of fipronil on male fertility: Insight into the mechanism of capacitation.
Reproductive Toxicology ( IF 3.3 ) Pub Date : 2020-04-12 , DOI: 10.1016/j.reprotox.2020.04.002
Jeong-Won Bae 1 , Woo-Sung Kwon 2
Affiliation  

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 GABAAR 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 GABAAR β-3. Only the ratio of GABAAR 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.

中文翻译:

研究氟虫腈对男性生育力的影响:洞察获能机制。

Fipronil(FPN)是一种广泛使用的苯基吡唑类农药,用于控制昆虫和清除兽用跳蚤,壁虱等。尽管FPN对人体健康构成中等危害,但人们在日常生活中仍很容易暴露。FPN通过阻止γ-氨基丁酸(GABA)和谷氨酸激活的氯离子通道来破坏昆虫的中枢神经系统。先前的研究表明,精子中存在GABA和GABAAR,它们在精子获能过程中扮演着各种角色,而精子获能是受精所必需的。但是,FPN对哺乳动物生育力的影响尚未完全了解。因此,本研究旨在研究FPN对精子的影响。在本文中,我们用小鼠精子治疗了各种浓度的FPN(0.1、1、10、100和300μM)或对照治疗。FPN治疗可显着降低精子活力,运动运动学参数和细胞内ATP水平,而顶体反应增强。磷酸-PKA和磷酸-酪氨酸底物的水平以剂量依赖性方式显着降低。同时,对照组和治疗组之间的GABAARβ-3水平没有差异。在FPN浓度较高时,只有GABAARβ-3pS408 / pS409的比例显着降低。此外,FPN治疗也可显着降低卵裂和囊胚形成率。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,从而导致不育。根据这些结果,
更新日期:2020-04-12
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