Creasy D M, Foster P M
Exp Mol Pathol. 1984 Apr;40(2):169-76. doi: 10.1016/0014-4800(84)90074-1.
The testicular effects of daily oral dosing with two glycol ethers--either ethylene glycol monomethyl ether (EGM) or monoethyl ether (EGE) were studied in the prepubertal rat by histological examination of the testes. Over the 11-day dosing period studied, EGM was found to produce testicular damage at dose levels of and in excess of 100 mg/kg/day with a no-effect level at 250 mg/kg/day. The findings at sequential time intervals throughout the dosing period indicated that primary spermatocytes undergoing pachytene development constituted the initial and major site of morphological damage. Within this population, differential sensitivity was demonstrated depending on the precise stage of meiotic maturation. A consistent order of spermatocyte susceptibility emerged from the results: dividing spermatocytes (Stage XIV) greater than early-pachytene spermatocytes (Stages I-III) greater than late-pachytene spermatocytes (Stages IX-XIII) greater than midpachytene spermatocytes (Stages IV-VIII). Leptotene/zygotene spermatocytes and Step 1 spermatids also showed degenerative changes but only after prolonged dosing at high-dose levels. The significance of the findings with respect to mechanisms of cellular toxicity in the testis is discussed.
通过对睾丸进行组织学检查，研究了在青春期前大鼠中每日口服两种二醇醚——乙二醇单甲醚（EGM）或单乙醚（EGE）对睾丸的影响。在所研究的11天给药期内，发现EGM在剂量水平达到及超过100mg/kg/天时会产生睾丸损伤，无作用水平为250mg/kg/天。在整个给药期的连续时间间隔的研究结果表明，处于粗线期发育的初级精母细胞是形态学损伤的初始和主要部位。在这个群体中，根据减数分裂成熟的精确阶段表现出不同的敏感性。结果显示出精母细胞易感性的一致顺序：正在分裂的精母细胞（第十四阶段）大于早粗线期精母细胞（第一至三阶段）大于晚粗线期精母细胞（第九至十三阶段）大于中粗线期精母细胞（第四至八阶段）。细线期/偶线期精母细胞和第一步精子细胞也显示出退行性变化，但仅在高剂量水平长期给药后才出现。讨论了这些发现对于睾丸细胞毒性机制的意义。
