Mechanism for the reduction in rat oocyte fertilizability after exposure to trichloroethylene, an environmental toxicant

Trichloroethylene (TCE) is commonly used as an industrial degreasing solvent, and as an ingredient in consumer products such as adhesives, spot removers, and paints. As a result of manufacturing, usage, and disposal practices, TCE is also an environmental toxicant. Environmental TCE primarily originates from release by industrial degreasing operations, as a result, TCE is a common ground and surface water contaminant in the United States. Humans can be exposed to TCE by inhalation, ingestion, and transdermal absorption. The body metabolizes TCE via two pathways: (1) cytochrome P450 dependent oxidation or (2) conjugation with glutathione. The ovary may be a unique target of TCF toxicity due to the presence of TCE metabolizing enzymes, such as cytochrome P450 2E1 and glutathione s-transferases. Earlier studies by our laboratory demonstrated that oocytes collected from female rats treated with TCE via drinking water are significantly less fertilizable compared with oocytes from vehicle-control females. Ovarian metabolism of TCE by cytochrome P450 dependent oxidation and/or glutathione conjugation may contribute to the reduction in oocyte fertilizability. The purpose of this dissertation research was three-fold: (1) to evaluate the rat ovary for evidence of TCE metabolism by the cytochrome P450 oxidative pathway, (2) to evaluate the rat ovary for evidence of TCE metabolism via the glutathione conjugation pathway, and (3) to examine whether in vivo TCE exposure induces alteration in ovarian gene expression which may result in modifications of proteins encoded by these genes. The hypothesis tested was TCE or its metabolites exert effects on transcription and/or post-translational modification of ovarian proteins, which subsequently prevents the normal series of fertilization events from occurring.