Gao Wen, Zhang Chen, Li Bichun, Oh Jeong Su
Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, South Korea.
College of Animal Science and Technology, Yangzhou University, Yangzhou, China.
Front Cell Dev Biol. 2022 Dec 2;10:1053654. doi: 10.3389/fcell.2022.1053654. eCollection 2022.
Fungicides are a type of pesticide used to protect plants and crops from pathogenic fungi. Azoxystrobin (AZO), a natural methoxyacrylate derived from strobilurin, is one of the most widely used fungicides in agriculture. AZO exerts its fungicidal activity by inhibiting mitochondrial respiration, but its cytotoxicity to mammalian oocytes has not been studied. In this study, we investigated the effect of AZO exposure on mouse oocyte maturation to elucidate the underlying mechanisms of its possible reproductive toxicity. We found that AZO exposure disturbed meiotic maturation by impairing spindle formation and chromosome alignment, which was associated with decreased microtubule organizing center (MTOC) integrity. Moreover, AZO exposure induced abnormal mitochondrial distribution and increased oxidative stress. The AZO-induced toxicity to oocytes was relieved by melatonin supplementation during meiotic maturation. Therefore, our results suggest that AZO exposure impairs oocyte maturation not only by increasing oxidative stress and mitochondrial dysfunction, but also by decreasing MTOC integrity and subsequent spindle formation and chromosome alignment.
杀菌剂是一种用于保护植物和作物免受病原真菌侵害的农药。嘧菌酯(AZO)是一种源自甲氧基丙烯酸酯类天然产物的甲氧基丙烯酸酯,是农业中使用最广泛的杀菌剂之一。AZO通过抑制线粒体呼吸发挥其杀菌活性,但其对哺乳动物卵母细胞的细胞毒性尚未得到研究。在本研究中,我们研究了AZO暴露对小鼠卵母细胞成熟的影响,以阐明其可能的生殖毒性的潜在机制。我们发现,AZO暴露通过损害纺锤体形成和染色体排列干扰减数分裂成熟,这与微管组织中心(MTOC)完整性降低有关。此外,AZO暴露诱导线粒体分布异常并增加氧化应激。在减数分裂成熟过程中补充褪黑素可减轻AZO对卵母细胞的毒性。因此,我们的结果表明,AZO暴露不仅通过增加氧化应激和线粒体功能障碍,还通过降低MTOC完整性以及随后的纺锤体形成和染色体排列来损害卵母细胞成熟。