The use of rat in vitro fertilization to detect reductions in the fertility of spermatozoa from males exposed to ethylene glycol monomethyl ether.
An in vitro fertilization (IVF) assay sensitive enough to detect changes in the fertilizing capacity of spermatozoa would be a useful tool with which to investigate the action of testicular toxicants. A known testicular toxicant, ethylene glycol monomethyl ether (EGME), was used to induce specific lesions in the germinal epithelium so that the ability of a rat IVF system to detect changes in fertility could be tested. Male rats were given single, oral doses of 50, 100, and 200 mg EGME/kg. Spermatozoa were recovered from the cauda epididymides of these males at intervals after treatment; their fertility was assessed using IVF, and the testes were processed for histologic examination. The fertility of the control males was consistently greater than 65%. Spermatozoa from males treated with EGME had reduced fertility at specific times after dosing. Thus, after 50 mg EGME/kg there was reduced fertility at 5 weeks; after 100 mg EGME/kg there was reduced fertility at 3.5, 4.5, 5, 6, and 6.5 weeks, and after 200 mg EGME/kg there was reduced fertility at 2 and 3 weeks, between 4.5 and 6 weeks, and at 7 weeks. This corresponded to damage to the elongated spermatids (2, 3, and 3.5 weeks), pachytene spermatocytes (4.5 to 6 weeks), and leptotene and preleptotene spermatocytes (7 weeks). This accords well with the data from serial breeding trials and reports of histologic damage after exposure to EGME. Therefore, using IVF it was possible to detect EGME-induced changes in fertilizing capacity which correlated closely with observations of testicular damage. It was also possible to demonstrate a clear dose response to EGME.
Holloway
A J
AJ
Institute of Zoology, Zoological Society of London, Regent's Park, England.
Moore
H D
HD
Foster
P M
PM
D000818:Animals; D005026:Ethylene Glycols / Q000633:toxicity*; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005307:Fertilization in Vitro; D008297:Male; D009865:Oocytes / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012671:Seminiferous Tubules / Q000473:pathology; D013094:Spermatozoa / Q000187:drug effects*
D005026:Ethylene Glycols; C005219:methyl cellosolve