Teratogenic and Embryocidal Effects of Zidovudine (AZT) in Sprague-Dawley Rats

[摘要] Objective:The purpose of the present investigation was to analyze the effets of zidovudine on thepostimplantation embryo and fetus.Methods:Pregnant Sprague-Dawley rats were given various doses (10 mg/kg, 30 mg/kg, 150mg/kg) of zidovudine or saline by an endotracheal tube during the period of embryogenesis (days6–8, 9–11, 6–11 postconception). The animals were sacrificed on days 18–19 of pregnancy, and theirfetuses were removed by hysterotomy. Autopsies under low (15×) and high (40×) power lightmicroscopy were performed on all fetuses.Results:There was no statistically significant difference among the groups with respect to maternalweight gain. There were more pregnancy resorptions in the group receiving high-dose zidovudine(150 mg/kg/day) throughout embryogenesis than in the control group (P= 0.001, respectively).Four major structural anomalies were noted among the 689 fetuses examined, but zidovudine wasnot associated with an increased frequency of congenital anomalies in rats when it was administeredin doses similar to, 3-, and 15-fold higher than the regimen recommended for adult humans. Thedrug, however, was embryocidal in the high-dose group (P= 0.002).Conclusions:These findings are consistent with previous studies of preimplantation mouse embryosthat demonstrated an embryocidal effect on preimplantation conceptuses. In summary, post-implantationembryonic zidovudine exposure was associated with significantly increased pregnancylosses (resorptions and intrauterine deaths).

[学科分类] 妇产科学