Concern has been raised regarding the toxic effects of various environmental chemical contaminants upon mammalian systems. Among these are organochlorine pesticides, such as O'-P'-DDT and chlordecone (Kepone), as well as the polychlorinated biphenyls (PCB) (Aroclor 1254) and the polybrominated biphenyls (PBB)(Fire Master Pb-6) and (TCDD). Accumulation and persistence of these toxicants in the biosphere have accentuated their public health significance in spite of limited commercial production or use. Although reproductive failure and abnormal embryogenesis have been the subject of previous investigators, no systematic studies have been directed at the causative factors for the infertility or embryonic anomalies. Because the early phases of pregnancy establishment are the most vulnerable to intervention by an altered hormonal environment they will be the focus of our attention. The hypothesis to be tested is: pregnancy failure in the rat following exposure to agents with known reproductive toxicity is due to altered embryo-uterine interactions at the time of implantation. Embryo development and its transport through the reproductive tract prior to implantation will be compared between treated and control animals. The effects of the agents, some of which are estrogenic, upon implantation in rats with functioning ovaries and adrenals will be compared with those in ovariectomized and hypophysectomized animals, in which preimplantation embryos are maintained by exogenous progesterone (P4). Transfer of preimplantation embryos exposed in vitro, or in the uterus of a donor mother, to the uteri of untreated pseudopregnant recipient females will indicate direct effects of the toxic agents upon the developing embryo. Exposure of the recipient female to the agents prior to transfer of the embryos from an untreated mother will reveal the effects due to an altered utero-embryo environment. The concentration of P4 in the serum, measured by radioimmunoassay (RIA), at various times after exposure to the toxic agents will indirectly evaluate their effects upon drug metabolizing enzymes. Assay of aryl hydrocarbon (benzo(a)-pyrene) hydroxylase activity in the uterus will be used as an index of possible steroid altering mechanisms induced by the toxic agents. Increased adrenal cortical function, which is detrimental to implantation, will be monitored by serum concentration of corticosterone (RIA). The results will aid our understanding of the mode of action of the environmental chemicals upon the early stages of pregnancy. Further, the results will contribute to our understanding of some of the basic aspects of implantation.
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