Permethrin may disrupt testosterone biosynthesis via mitochondrial membrane damage of Leydig cells in adult male mouse.
Permethrin may disrupt testosterone biosynthesis via mitochondrial membrane damage of Leydig cells in adult male mouse.
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DOI：
10.1210/en.2006-1497
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发表时间：
2007-08
期刊：
影响因子：
4.8
通讯作者：
Shu-Yun Zhang;Yuki Ito;O. Yamanoshita;Y. Yanagiba;M. Kobayashi;K. Taya;Chunmei Li;Ai Okamura
中科院分区：
文献类型：
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作者：
Shu-Yun Zhang;Yuki Ito;O. Yamanoshita;Y. Yanagiba;M. Kobayashi;K. Taya;Chunmei Li;Ai Okamura
氯氰菊酯是一种常用的拟除虫菊酯类拟除虫菊酯杀虫剂，广泛用于控制农业、林业、家庭、园艺和公共卫生中的有害昆虫，具有环境暴露的风险。在这里，我们评估了顺式氯菊酯对成年雄性ICR小鼠的生殖毒性，这些小鼠口服顺式氯氰菊酯(0、35或70 mg/kg d)6wk。治疗组尾附睾精子数和精子活动率均呈剂量依赖性下降。随着黄体生成素水平的增加，睾丸睾酮生成量和血浆睾酮浓度显著降低，且呈剂量依赖关系。染毒后小鼠睾丸内睾酮水平与顺式氯氰菊酯残留量呈显著回归关系。然而，顺式氯氰菊酯处理后，大鼠的体重、生殖器官绝对和相对重量、精子形态和血浆FSH浓度均无明显变化。此外，顺式氯氰菊酯暴露显著降低睾丸线粒体外周血苯二氮受体(PBR)、类固醇合成急性调节蛋白(STAR)和细胞色素P450侧链裂解(P450scc)的mRNA表达水平，以及STAR和P450scc的酶和蛋白表达水平。在电子显微镜水平上，暴露组小鼠睾丸间质细胞线粒体膜损伤。我们的结果表明，杀虫剂氯菊酯可能通过减少胆固醇向线粒体的输送，减少细胞内胆固醇到孕烯醇酮的转化，从而减少随后的睾酮产生，从而导致间质细胞线粒体膜损伤，扰乱睾酮的生物合成。
Permethrin, a popular synthetic pyrethroid insecticide used to control noxious insects in agriculture, forestry, households, horticulture, and public health throughout the world, poses risks of environmental exposure. Here we evaluate the reproductive toxicity of cis-permethrin in adult male ICR mice that were orally administered cis-permethrin (0, 35, or 70 mg/kg d) for 6 wk. Caudal epididymal sperm count and sperm motility in the treated groups were statistically reduced in a dose-dependent manner. Testicular testosterone production and plasma testosterone concentration were significantly and dose-dependently decreased with an increase in LH, and a significant regression was observed between testosterone levels and cis-permethrin residues in individual mice testes after exposure. However, no significant changes were observed in body weight, reproductive organ absolute and relative weights, sperm morphology, and plasma FSH concentration after cis-permethrin treatment. Moreover, cis-permethrin exposure significantly diminished the testicular mitochondrial mRNA expression levels of peripheral benzodiazepine receptor (PBR), steroidogenic acute regulatory protein (StAR), and cytochrome P450 side-chain cleavage (P450scc) and enzyme and protein expression levels of StAR and P450scc. At the electron microscopic level, mitochondrial membrane damage was found in Leydig cells of the exposed mouse testis. Our results suggest that the insecticide permethrin may cause mitochondrial membrane impairment in Leydig cells and disrupt testosterone biosynthesis by diminishing the delivery of cholesterol into the mitochondria and decreasing the conversion of cholesterol to pregnenolone in the cells, thus reducing subsequent testosterone production.