Chemical exposure of embryos during the preimplantation stages of pregnancy: Mortality rate and intrauterine development

Exposure of CD-1 mouse embryos at the eight- to 16-cell stage for 1 hour to methylmethanesulfonate (MMS; 0.25, 0.5, and 1.0 nM) produced DNA breakage and interfered with embryonic development in a dose-related manner. MMS-exposed blastocysts were transferred to oviducts of untreated recipient female mice, and the conceptuses were allowed to develop to term. MMS exposure resulted in an increased intrauterine death rate, although the number of implantation sites was not decreased. Surviving MMS-treated offspring showed intrauterine growth retardation, but there was no increase in the incidence of gross abnormalities. Intrauterine growth retardation, without an increase in gross abnormalities, was also observed in the offspring of pregnant New Zealand White rabbits dosed during the preimplantation stages of pregnancy with an “environmental cocktail” composed of ethanol, nicotine, caffeine, sodium salicylate, and dichloro-diphenyl-trichloro-ethane (DDT). When the compounds were tested individually, nicotine and DDT were the only two that produced intrauterine growth retardation. DDT-treated 8-day rabbit conceptuses were smaller than controls and showed abnormal persistence of preimplantation proteins in the yolk sac fluid. These results suggest that exposure to chemicals during the preimplantation stages of pregnancy may result in a cessation of growth and development before implantation or during later intrauterine development. Damage can be repaired but it may result in offspring that show intrauterine growth retardation without gross abnormalities.