This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The critical role of microRNAs (miRNAs) in human development is becoming increasingly clear, as these small, non-coding RNAs are responsible for gene regulation critical in developmental patterning and timing. Although studies have shown that alteration of these miRNAs can contribute to developmental problems, as well as to carcinogenesis, little work has addressed the mechanism by which the profile of miRNA expression is altered, nor if exposures known to be capable of eliciting these phenotypic disorders do so through alteration of miRNA expression. This proposal seeks to examine this question, by examining the impact of exposure to two well-defined environmental endocrine disruptors, methoxychlor, an estrogenic/anti-estrogenic pesticide, and vinclozolin, an anti-androgenic fungicide on cell lines derived from the male reproductive tract. Using array-based technology, it will be possible to examine the hypothesis that these compounds will alter the miRNA expression pattern in male reproductive tract cell lines, and that the pattern of alteration will differ by the cell line's tissue of origin. Also, it is hypothesized that the specific miRNAs altered will differ due to the different endocrine-effecting properties of these endocrine disrupting chemicals (anti-androgenic vs. estrogenic/anti-estrogenic). These results will provide insight into a novel toxicologic mode of action of these compounds.
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