Chapin R E, Dutton S L, Ross M D, Lamb J C
Fundam Appl Toxicol. 1985 Feb;5(1):182-9. doi: 10.1016/0272-0590(85)90063-6.
Previous histologic studies on the effects of EGME identified dividing spermatocytes as a primary target cell type in the testis. The following studies were undertaken to assess possible effects of EGME on late-stage and epididymal spermatids, and spermatogonia. Adult male F344 rats (n = 20/group) of proven fertility were dosed po with 0, 50, 100, or 200 mg EGME/kg/day for 5 days. Each male was then mated with two females/week for 8 weeks. Females were sacrificed ca. 2 weeks after removal from the male, and number of live and dead fetuses, resorption sites, and corpora lutea were noted. Additional males were treated similarly, sacrificed at weekly intervals, and measures of epididymal sperm count, motility, and morphology were made. The fertility of males treated with 200 mg EGME/kg declined at Week 4, and remained low for the rest of the study. There was a modest but significant increase in the number of resorption sites at Weeks 5 and 6 in the high dose group. There was a decrease in the number of litters sired at Week 5 after dosing in the 100-mg EGME/kg group. There were time- and dose-related decreases in sperm concentration and motility, primarily in the 100- and 200-mg/kg groups, as well as concurrent elevations in the number of abnormal sperm forms in the epididymis. These studies show that EGME is a very weak inducer of dominant-lethal mutations, and produces previously undescribed effects on late-stage spermatids and spermatogonia.
先前关于乙二醇甲醚(EGME)作用的组织学研究确定,分裂中的精母细胞是睾丸中的主要靶细胞类型。接下来进行的研究旨在评估EGME对晚期和附睾精子细胞以及精原细胞可能产生的影响。选用成年且生育能力已得到证实的雄性F344大鼠(每组n = 20),经口给予0、50、100或200毫克EGME/千克/天,持续5天。之后,每只雄性大鼠每周与两只雌性大鼠交配,持续8周。雌性大鼠在与雄性大鼠分离约2周后处死,记录活胎和死胎数量、吸收位点以及黄体数量。另外一些雄性大鼠接受类似处理,每周处死,测量附睾精子计数、活力和形态。接受200毫克EGME/千克处理的雄性大鼠在第4周生育能力下降,且在研究剩余时间内一直保持在较低水平。高剂量组在第5周和第6周时吸收位点数量有适度但显著的增加。给予100毫克EGME/千克处理的大鼠在给药后第5周产仔数减少。精子浓度和活力出现与时间和剂量相关的下降,主要出现在100毫克/千克和200毫克/千克组,同时附睾中异常精子形态数量增加。这些研究表明,EGME是一种非常弱的显性致死突变诱导剂,并且对晚期精子细胞和精原细胞产生了先前未描述的影响。