Although the testicular cytotoxicity of methotrexate has been evaluate
d in the rat, previous models have utilized routes other than the intr
avenous one, and have generally employed multiple-dose regimens. In th
is report, we describe testicular toxicity in the Sprague-Dawley rat f
ollowing a single intravenous bolus of methotrexate (0-700 mg/kg body
weight [BW]), with necropsy 56 days later. Testicular toxicity was eva
luated qualitatively by histology and quantitatively by testicular wei
ght, sperm head count, modified Johnsen score, repopulation index, and
epididymal index. Effects of methotrexate on heart, lung, liver, and
kidney histology were evaluated qualitatively. Oligospermia occurred a
t low and intermediate dosages of methotrexate, but testicular atrophy
was not observed. LD50 at day five for methotrexate appears to be app
roximately 300 mg/kg BW using this regimen. This model will facilitate
the study of techniques to avoid drug-induced testicular damage. (C)
1994 Wiley-Liss, Inc.