Study on the mechanisms of the reproductive damages caused by glycol ethers using transgenic mouse

转基因小鼠乙二醇醚生殖损伤机制研究

• 批准号: 17590529
• 负责人: WANG Rui-Sheng
• 金额: $ 2.27万
• 依托单位: National Institute of Occupational Safety and Health, Japan
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17590529/
• 关键词: glycol ethers; ethylene glycol monoethyl ether; organic solvent; reproductive toxicity; Aldh2; transgenic mouse; ALDH2遺伝子; ノックアウトマウス; 精子運動能; エチレングリコールモノエチル

Ethylene glycol monoethyl ether (EGEE) can cause damage to testes and sperm, and its metabolites are believed to play an important role in its toxicity. Aldehyde dehydrogenase 2 (ALDH2) is involved in the metabolism of this chemical. To investigate whether and how the enzyme affects the toxicity of EGEE, we conducted experiments comparing Aldh2 knockout mice with wild-type mice. Administration of EGEE at 100 and 600mg/kg/day for one week did not induce any significant change in the weight and body weight ratios of testes, prostate and epididymides in either Aldh2 knockout or wild-type mice. However, motion of sperm from the spermaduct, as analyzed with a Hamilton-Thorne Sperm analyzer, was slightly decreased in the low dose group, and significantly lower in the high dose group; and the percentage of progressive sperm was also reduced in the two EGEE groups. This effect of EGEE treatment was observed in the wild-type, but not in the Aldh2 knockout mice. Sperm motion from the cauda epididymides was not affected. On the other hand, the concentration of ethoxyacetic acid, a metabolite of EGEE, in 24h pooled urine of EGEE-treated Aldh2 knockout mice was not significantly lower than that of the wild-type mice on most days of urine sampling. These results suggest that inactivation of the ALDH2 enzyme due to gene mutation may be linked to differences in the susceptibility to EGEE-induced sperm toxicity.

乙二醇单乙醚（EGEE）会对睾丸和精子造成损害，其代谢物被认为在其毒性中发挥了重要作用。乙醛脱氢酶 2 (ALDH2) 参与该化学物质的代谢。为了研究该酶是否以及如何影响 EGEE 的毒性，我们进行了实验，将 Aldh2 敲除小鼠与野生型小鼠进行比较。在 Aldh2 敲除小鼠或野生型小鼠中，以 100 和 600mg/kg/天的 EGEE 给药一周，并未引起睾丸、前列腺和附睾的重量和体重比的任何显着变化。然而，用汉密尔顿-索恩精子分析仪分析，低剂量组中精子从输精管的运动略有减少，而高剂量组则显着降低。在两个 EGEE 组中，进步精子的百分比也有所减少。 EGEE 治疗的这种效果在野生型小鼠中观察到，但在 Aldh2 敲除小鼠中没有观察到。附睾尾部的精子运动不受影响。另一方面，EGEE处理的Aldh2敲除小鼠24小时合并尿液中EGEE的代谢物乙氧基乙酸的浓度在大部分尿液采样天数中并不显着低于野生型小鼠。这些结果表明，基因突变导致的 ALDH2 酶失活可能与 EGEE 诱导的精子毒性的易感性差异有关。