A quantitative study of stage-specific spermatocyte damage following administration of ethylene glycol monomethyl ether in the rat

Abstract

A quantitative study has been carried out to characterize the stage susceptibility of the spermatocyte to ethylene glycol monomethyl ether (EGM) toxicity. EGM was administered as a single oral dose of 250 mg/kg body wt and rats were examined at time periods after dosing. The number of spermatocytes and round spermatids in tubules at each stage of spermatogenesis was counted. A sharp transition in susceptibility was observed between zygotene spermatocytes in stage XIV which showed no effect and pachytene spermatocytes in stage I which showed death or depletion of 70% of its population after 1 day. A similar transition was seen between dividing spermatocytes and step 1 spermatids, the latter being unaffected. There was a gradual reduction in susceptibility toward midpachytene such that cells in stages VII-XI showed no effect. Analysis of later time periods revealed no effect on spermatogonia or prepachytene spermatocytes but did indicate that midpachytene spermatocytes underwent delayed cell death after further progression through the cycle. In a separate sequential morphological study of early changes, the earliest signs of necrosis were seen 12 hr after dosing and were restricted to spermatocytes in stages V, XI, and XII. Cell death then progressed in a wave-like manner through stages XIII and XIV finally reaching stage I, 24 hr after dosing.