Reproduction and development are highly integrated, hormonally dependent processes that can be acutely sensitive to chemical insult. Several halogenated polycyclic aromatic hydrocarbons, which are common Superfund contaminants, exhibit agonist as well as antagonist hormonal activity and are therefore potential reproductive and developmental toxicants. This project is composed of three subprojects. Each subproject has a different approach to the study of reproductive toxicity, yet the subprojects share the overall objectives of (1) characterizing the effects of selected halogenated polycyclic aromatic hydrocarbons on reproduction and development, (2) investigating the mechanisms that initiate and mediate the chemical-induced alterations in reproduction and development, (3) assessing possible health risks arising from exposure to these chemicals. This subproject will focus on the process of parturition, investigating the potential role of PCBs in prematurity, post-maturity and dystocia (difficult labor). The proposed research will test the hypothesis that PCBs modulate uterine contraction in a direct and congener-specific manner, and that these PCBs thereby also have the potential to alter parturition. PCBs will first be assessed for effects on contraction of isolated uterine strips followed by in vivo experiments to determine if the PCB modifies parturition. Additionally, the mechanism(s) of action of the PCBs will be examined. It is hypothesized that direct actions of PCBs on uterine contraction are due to mechanisms involving steroidogenic action, gap junctional communication, calcium homeostasis, and/or glutathione status, possibly in an interactive manner.
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