MICRORNA REGULATION OF DEVELOPMENT AND FUNCTION OF THE FEMALE REPRODUCTIVE TRACT

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 子宫是所有高等物种成功繁殖所必需的。了解促进子宫发育和功能的分子机制对于成功繁殖是至关重要的。 DICER是一种酶，它产生microRNAs(MiRNAs)，并共同调节特定基因产物的转录后调控。最近，miRNAs被认为在胚胎着床、人类子宫内膜以及女性子宫内膜异位症的病理生理学中发挥作用。综上所述，这些研究表明，DICER及其酶产物(即miRNAs)在多器官系统的分子调控中发挥着关键作用，包括生殖功能，特别是子宫着床和子宫病理生理状况。 在拟议的应用中要检验的总体假设是，通过加工miRNAs的RNaseIII核酸内切酶DICER在出生后子宫发育和功能中起着至关重要的作用。为了验证这一假说，我们制定了两个具体的目标：1)通过干扰Dier的表达来确定Dird/miRNAs在出生后子宫发育和功能中的功能作用；2)确定影响出生后子宫发育和功能的特定miRNAs。为了实现这些目标，我们将利用突变小鼠，在这些突变小鼠中，迪格尔已经有条件地从雌性生殖道中删除。主要成果措施将包括评估女性生殖道的外观和功能(目标一)，并确定导致预期发育/功能异常的miRNAs和/或其蛋白质靶标。

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.