Exposure to chlorpyrifos leads to spindle disorganization and mitochondrial dysfunction of porcine oocytes during in vitro maturation
Exposure to chlorpyrifos leads to spindle disorganization and mitochondrial dysfunction of porcine oocytes during in vitro maturation
复制标题
DOI：
10.1016/j.theriogenology.2021.08.007
复制
发表时间：
2021-08-13
期刊：
影响因子：
2.8
通讯作者：
Ju, Shiqiang
中科院分区：
文献类型：
--
作者：
Jiang, Yao;He, Yijing;Ju, Shiqiang
毒死蜱（Chlorpyrifos，CPF）是农业和家庭环境中应用最广泛的有机磷农药之一，对人畜健康构成潜在威胁。CPF的各种生殖毒性已被报道，然而，很少有信息CPF暴露是否会对哺乳动物卵母细胞产生毒性作用。本文研究了CPF对猪卵母细胞减数分裂成熟和发育能力的影响，并对其可能的毒性机制进行了探讨。在体外成熟（IVM）过程中，用0、5、10和20 mM的CPF处理猪卵丘-卵母细胞复合体（COCs）44 h，结果表明，当CPF浓度达到10 mM时，第一极体（PB 1）排出率显著降低，所获得的中期II（MII）卵母细胞的后续发育能力也受到损害。较高百分比的暴露于CPF的卵母细胞被阻滞在后期-末期I（ATI）阶段，伴随着染色体错位和异常纺锤体。CPF处理的卵母细胞中活性氧水平升高，抗氧化相关基因（CAT、SOD 1、SOD 2、GPX）表达上调。此外，CPF处理导致线粒体膜电位（MMP）的去极化和细胞色素c（Cyt c）的释放。同时，CFP处理后卵母细胞凋亡率显著增加，Bax和CASPASE 3表达水平显著上调。总之，暴露于10 mM CPF可破坏减数分裂周期进程，导致异常纺锤体和线粒体功能障碍，最终诱导猪卵母细胞的氧化应激和凋亡。(c)2021爱思唯尔公司All rights reserved.
Chlorpyrifos (CPF), as one of the most extensively applied organophosphorus pesticides (OPs) in agricultural and domestic settings, causes a potential threat to human and animal health. Various reproductive toxicities of CPF have been reported, however, little information is available on whether CPF exposure could exert toxic effects on mammalian oocytes. Herein, the effects of CPF on the meiotic maturation and developmental capability of porcine oocytes were investigated, and the possible toxic mechanisms of CPF were also explored. Porcine cumulus-oocyte complexes (COCs) were treated with 0, 5, 10, or 20 mM CPF for 44 h during in vitro maturation (IVM), and the results showed that the first polar body (PB1) extrusion rate was significantly decreased, and the subsequent developmental competence of the resulting metaphase II (MII) oocytes was also impaired when the concentration of CPF reached 10 mM. In addition, a higher percentage of CPF-exposed oocytes were arrested at the anaphase-telophase I (ATI) stage, accompanied by misaligned chromosomes and aberrant spindles. Furthermore, higher levels of ROS and upregulated antioxidant-related genes (CAT , SOD1, SOD2 , GPX) were detected in CPFtreated oocytes. Additionally, CPF treatment led to the depolarization of mitochondrial membrane potential (MMP) and the release of cytochrome c (Cyt c). Simultaneously, the apoptotic rate of the oocytes was significantly increased, and the expression levels of Bax and CASPASE3 were significantly upregulated after CFP exposure. Together, exposure to 10 mM CPF can disrupt the meiotic cycle progression, lead to aberrant spindles and mitochondrial dysfunction, which eventually induce oxidative stress and apoptosis in porcine oocytes. (c) 2021 Elsevier Inc. All rights reserved.