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The effect of diazepam on meiosis in the CF-1 mouse.

Oocytes from virgin CF-1 female mice were treated in vitro with Krebs-Ringer media containing 1.0, 10.0, 30.0, 50.0, 100.0, and 200.0 μg/ml of diazepam. In addition, oocytes were exposed to no drug and to 4% propylene glycol and Krebs-Ringer media. The latter was chosen because diazepam is frequently injected in a propylene glycol vehicle. After 17 hours of incubation at 37°C in a 5% C02 atmosphere, all oocytes were scored for the presence of germinal vesicles, Metaphase I, Metaphase II, or degenerative and abnormal forms. Cells from the pure control, propylene glycol, 1.0, and 10.0 μg/ml concentration preparations demonstrated progress to Metaphase II in from 86–89% of cells. Only a small percentage of oocytes was noted to be degenerative or abnormal in any of these groups. From 0.6–2% of oocytes were arrested in Metaphase I. At 30.0 μg/ml concentration 18.7% of cells were arrested at Metaphase I but only 1.5% were noted to be degenerated. At 50.0 μg/ml, 26.6% of cells were arrested at Metaphase I and 13.3% were degenerated. At 100.0 μg, 7.7% of cells were found in Metaphase I, 9.2% in Metaphase II, and 67.7% degenerated. At 200.0 μg/ml 3.1% of cells were found at Metaphase I, none at Metaphase II, and 88% in the degenerative form. Since blood levels of diazepam rarely rise above 6 μg/ml even in patients treated with as much as 200 mg per day, and are generally observed in the 1 μg/ ml range for patients on typical treatment regimen, it is not likely that human tissues will achieve concentrations seen to have toxic effects in these studies. Future in vivo studies, however, seem indicated.