Experimentally-induced Exencephaly and Spina Bifida in Mice

Background– An agent that many pregnant women may be exposed to is opium or one of its alkaloids such as morphine and heroin. Recent observations of central nervous system (CNS) defects such as cyclopia among the infants of addicted mothers have suggested that opiate agents might be a cause of neural tube defects. The purpose of this study was to test morphine for CNS teratogenicity in mice and to identify the primordial structures affected. Methods– Timed pregnant BALB/c mice were intraperitoneally injected with 10 mg/kg morphine given in the early morning on days 10 and 11 of gestation. After dissection of fetuses and fixation in Bouin’s or 10% formalin solution, CNS abnormalities were evaluated using a dissecting microscope. Data were analyzed using Fisher’s exact test. Results– There was a higher incidence of CNS fetal malformations including exencephaly and spina bifida in fetuses whose mothers were exposed to morphine than in control fetuses exposed to NaCl. There were defects in 33% of fetuses from mothers who received morphine on both days 10 and 11 of gestation.Conclusion– Critical morphine injection times were determined to be days 10 to 11 of gestation. Our results indicate that morphine can be embryopathic during critical stages of CNS development.