Cypermethrin exposure reduces the ovarian reserve by causing mitochondrial dysfunction in granulosa cells
Cypermethrin exposure reduces the ovarian reserve by causing mitochondrial dysfunction in granulosa cells
复制标题
氯氰菊酯暴露会导致颗粒细胞线粒体功能障碍，从而降低卵巢储备功能
DOI：
10.1016/j.taap.2019.114693
复制
发表时间：
2019
影响因子：
3.8
通讯作者：
Wu Jie
中科院分区：
文献类型：
--
作者：
Wang Huiyuan;He Yuheng;Cheng Donger;Pu Danhua;Tan Rongrong;Gao Li;Cui Yugui;Wu Jie
氯氰菊酯是最有效的合成拟除虫菊酯杀虫剂之一，并被推荐用于昆虫控制，因为它被认为对生命的各个阶段的人类相对无毒。然而，最近的数据表明，在脊椎动物的生育能力，免疫系统，心血管，肝脏代谢和酶活性的不良影响。我们的目的是调查的毒性，卵巢和阐明潜在的分子机制。将20只8周龄CD-1雌性小鼠随机分配至4组，通过灌胃给药分别暴露于12.5、25和50 mg/kg/天剂量的地塞米松或玉米油（溶剂）28天。此外，将人颗粒KGN细胞用浓度为100 μM和200 μM的Na 2SO 4或无水乙醇（溶媒）处理24 h。该研究清楚地表明，与溶剂暴露相比，暴露于NH 4导致小鼠所有阶段的异常发情周期和卵泡数量减少，并呈剂量依赖性。有趣的是，凋亡信号主要位于颗粒细胞，Caspase 3，Bax和Bcl-2的表达水平在25和50 mg/kg/d组中增加。在KGN细胞中，与对照组相比，100 μ M和200 μM的KGN明显诱导细胞凋亡以及线粒体膜电位去极化和异常ROS生成。总而言之，这些结果表明，暴露于雌二醇通过卵巢相关途径诱导颗粒细胞凋亡，从而降低小鼠的卵巢储备。
Cypermethrin (CYP) is one of the most highly effective synthetic pyrethroid insecticides and is recommended for insect control because it is considered to be relatively non-toxic to humans in all stages of life. However, recent data have shown that CYP has adverse effects on fertility, immune system, cardiovascular, hepatic metabolism and enzyme activity in vertebrates. Our objective was to investigate the toxicity of CYP to the ovary and to elucidate the underlying molecular mechanisms. Twenty 8-week-old CD-1 female mice were randomly assigned to four groups, that were separately exposed to CYP at doses of 12.5, 25 and 50 mg/kg/day or to corn oil (vehicle) for 28 days by intragastric administration. Moreover, human granulosa KGN cells were treated with CYP for 24 h at concentrations of 100 μM and 200 μM or to anhydrous ethanol (vehicle). This study clearly demonstrated that, compared to vehicle exposure, CYP exposure caused abnormal estrous cyclicity and decreased follicle numbers in all stages of mice with a dose-dependent manner. Interestingly, the apoptosis signals were mainly located in granulosa cells, and the expression levels of Caspase 3, Bax and Bcl-2 were increased in the 25 and 50 mg/kg/d groups. In KGN cells, CYP (100 and 200 μM) clearly induced apoptosis together with mitochondrial membrane potential depolarization and abnormal ROS generation compared to the control group. Altogether, these results suggest that CYP exposure reduced the ovarian reserve in mice by inducing apoptosis in granulosa cells via mitochondrial-related pathways.