EFFECT OF ZIDOVUDINE ON PREIMPLANTATION MURINE EMBRYOS

It previously has been demonstrated that zidovudine (AZT) is lethal to early murine embryos. The effect of the drug on pre- and postimplanta tion embryos was examined to delineate the timing of this toxicity and to investigate its possible mechanisms. Embryos exposed in the whole mouse during preblastocyst development were unable to proceed beyond t he blastocyst stage. Similarly, when two-cell embryos harvested from u nexposed females were exposed to low-concentration (1 muM) AZT in vitr o over 24 h, development beyond the blastocyst stage was inhibited. In contrast, drug exposure during in vitro blastocyst and postblastocyst development resulted in little or no morphologic toxicity. Further in vestigation revealed that preblastocyst AZT exposure resulted in the d evelopment of blastocysts with significantly lower cell numbers than c ontrol embryos. While embryonic exposure to AZT at the blastocyst and postblastocyst stages also resulted in retarded cell division, the eff ects were milder than those recorded after preblastocyst exposure. The se data demonstrate that the critical period of AZT toxicity toward mu rine embryos is between ovulation and implantation and indicate that A ZT direct suppresses cell division in the preimplantation embryo.