REPRODUCTIVE TOXICOLOGY OF ENVIRONMENTAL MUTAGENS

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A model system to study the risk from chemical exposure to developing preimplantation embryos has been developed. Both short-term and long-term effects of such exposure can be studied. Traditionally, it was thought that exposure of pregnant females to toxic substances during the preimplantation period is without consequence either because the compound cannot reach the cleaving egg or because the embryo is killed by the exposure. We have looked at the effects of chemicals known to cause either birth defects or tumor formation. We have exposed preimplantation embryos (blastocysts) in vitro and have demonstrated a significant decrease in incorporation of radiolabeled precursors of RNA, DNA, and protein in viable, treated embryos. We know from specific labeling experiments that this compound is taken up by the mouse blastocyst. We hope soon to place exposed embryos in the uteri of pseudopregnant foster mothers. With such embryo transfer experiments, it will be possible to determine the effects of exposure to environmental carcinogens on implantation rate, birth rates and the relation of such exposure to birth defects. These techniques are easily applicable to other environmentally relevant compounds, in order to determine potential risk of exposure for the embryo in the early periods of development at a time when the pregnant mother is unaware of her pregnancy. The role of the endometrium in activating the carcinogens will be investigated utilizing endometrial cell-culture systems.