The morphological development of glycol ether-induced testicular atrophy in the rat

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.