MICRORNA REGULATION OF DEVELOPMENT AND FUNCTION OF THE FEMALE REPRODUCTIVE TRACT

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The uterus is necessary for successful propagation of all higher species. Understanding the molecular mechanisms that contribute to the development and function of the uterus is essential for successful reproduction. Dicer is an enzyme that generates microRNAs (miRNAs) and together regulatet post-transcriptional regulation of specific gene products. Recently, miRNAs have been proposed to play a role in embryo implantation as well as in the human endometrium and in the pathophysiology of the female disease endometriosis. Collectively, these studies suggest that Dicer and it's enzymatic products (i.e. miRNAs) play a pivotal role in the molecular regulation of multiple organ systems, including reproductive function and specifically uterine implantation and uterine pathophysiological conditions. The overall hypothesis to be tested in the proposed application is that the RNase III endonucleases, Dicer, through processing of miRNAs plays a vital role in post-natal uterine development and function. To test this hypothesis, we have formulated two specific aims which will: 1) determine the functional role of Dicer/miRNAs in post-natal uterine development and function by disrupting Dicer expression and 2) identify specific miRNAs that impact post-natal uterine development and function. To accomplish these goals we will utilize mutant mice in which Dicer has been conditionally deleted from the female reproductive tract. The main outcome measures will include assessment of the appearance and function of the female reproductive tract (Aim I) and identifying the miRNAs and/or their protein targets which lead to the anticipated developmental/functional abnormalities.