Oudiz D, Zenick H
Toxicol Appl Pharmacol. 1986 Jul;84(3):576-83. doi: 10.1016/0041-008x(86)90263-2.
2-Ethoxyethanol (EE), a member of the glycol ethers, has been shown to produce testicular atrophy in laboratory animals. The present study further identified the spectrum of effects on the male reproductive system in vivo and initiated in vitro studies on possible mechanisms of action. Adult, male rats were treated (po) with 0 or 936 mg EE/kg, 5 days/week for 6 weeks. Semen samples were collected on a weekly basis during the exposure period from ovariectomized, hormonally primed females immediately following mating and analyzed for sperm count, sperm morphology, and sperm motility. Sperm count and percent normal morphology were decreased at Weeks 5 and 6, and sperm motility was decreased at Week 6. These data, along with other studies, indicated that the pachytene spermatocyte was the most sensitive target for EE. In vitro studies monitored O2 consumption and ATP concentrations in isolated pachytene spermatocytes which were treated with 10 mM EE or 1 or 10 mM ethoxyacetic acid (EAA), the reported active metabolite of EE. An increase in respiratory ratio for the lactate rate/endogenous rate and a decrease in the 2,4-dinitrophenol rate/lactate rate were observed only for cells treated with 10 mM EAA. Additionally, a decrease in ATP concentration was seen only with 10 mM EAA. These results indicated that EAA interfered with energy metabolism in the pachytene spermatocyte. This effect may, in part, explain the testicular toxicity produced by this compound.
2-乙氧基乙醇（EE）是二醇醚类的一员，已被证明可使实验动物发生睾丸萎缩。本研究进一步确定了其对雄性生殖系统的体内作用谱，并启动了关于可能作用机制的体外研究。成年雄性大鼠每周5天、连续6周经口给予0或936 mg EE/kg。在暴露期间，每周从切除卵巢并用激素预处理的雌性大鼠交配后立即采集精液样本，分析精子数量、精子形态和精子活力。在第5周和第6周时精子数量和正常形态百分比降低，在第6周时精子活力降低。这些数据以及其他研究表明，粗线期精母细胞是EE最敏感的靶标。体外研究监测了用10 mM EE或1或10 mM乙氧基乙酸（EAA，报道的EE活性代谢产物）处理的分离粗线期精母细胞中的氧气消耗和ATP浓度。仅在用10 mM EAA处理的细胞中观察到乳酸率/内源性率的呼吸比率增加以及2,4-二硝基苯酚率/乳酸率降低。此外，仅在10 mM EAA处理时观察到ATP浓度降低。这些结果表明EAA干扰了粗线期精母细胞中的能量代谢。这种作用可能部分解释了该化合物产生的睾丸毒性。
