Effects of Ethylene Glycol Monomethyl Ether (EGME) on Mating Performance and Epididymal Sperm Parameters in F344 Rats

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.