Reproductive and Teratogenic Effects of Nitrous Oxide, Fentanyl and Their Combination in Sprague-Dawley Rats

Abstract

The reproductive and teratogenic effects of 35% and 50% nitrous oxide, fentanyl 500 micrograms kg-1/day and their combinations were studied using a total of 419 timed-pregnant Sprague-Dawley rats. On day 7 of pregnancy, osmotic minipumps which delivered either fentanyl 500 micrograms kg-1/day or normal saline for 2 weeks were implanted subcutaneously in the back of the rats. Animals then were exposed to air, 35% nitrous oxide or 50% nitrous oxide for 24 h on day 9 of pregnancy. On day 21 of pregnancy, Caesarean sections were performed and all 2693 offspring were preserved and subsequently examined microscopically for external, visceral and skeletal abnormalities. There were no reproductive or teratogenic effects observed with 35% nitrous oxide, but adverse effects were observed with 50% nitrous oxide. The addition of fentanyl to the nitrous oxide increased the mortality rate among the rats, but did not significantly add to the adverse reproductive or teratogenic effects of nitrous oxide.