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 (15×) and high (40×) 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).