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

OBJECTIVE The purpose of the present investigation was to analyze the effets of zidovudine on the postimplantation embryo and fetus. METHODS Pregnant Sprague-Dawley rats were given various doses (10 mg/kg, 30 mg/kg, 150 mg/kg) of zidovudine or saline by an endotracheal tube during the period of embryogenesis (days 6-8, 9-11, 6-11 postconception). The animals were sacrificed on days 18-19 of pregnancy, and their fetuses were removed by hysterotomy. Autopsies under low (15x) and high (40x) power light microscopy were performed on all fetuses. RESULTS There was no statistically significant difference among the groups with respect to maternal weight 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 was not associated with an increased frequency of congenital anomalies in rats when it was administered in doses similar to, 3-, and 15-fold higher than the regimen recommended for adult humans. The drug, however, was embryocidal in the high-dose group (P = 0.002). CONCLUSIONS These findings are consistent with previous studies of preimplantation mouse embryos that demonstrated an embryocidal effect on preimplantation conceptuses. In summary, post-implantation embryonic zidovudine exposure was associated with significantly increased pregnancy losses (resorptions and intrauterine deaths).