Abstract
MicroRNAs are 22-nucleotide molecules which are hypothesized to regulate specific mRNA sequences. MicroRNAs play important roles in differentiation, proliferation, and development. However, their roles in normal and reproductive tract disease states are largely unknown. To investigate the role of microRNAs in the pathogenesis of endometriosis, we have undertaken a multi-platform, genome-wide approach. We collected samples of ectopic and eutopic endometrium from women with and without endometriosis. Using next generation microRNA sequencing and transcriptome analysis in combination with publically available targeting databases, we generated a list of microRNA:mRNA pairs potentially involved in endometriosis. We have begun to validate the functional nature of these microRNA:mRNA pairs in vitro using primary human endometrial stromal cell cultures. Using this next generation technology, we also discovered 47 novel microRNAs in eutopic and ectopic endometrial tissues. In addition, to study the global role of microRNAs in reproductive tissues, we have created a conditional knockout mouse model lacking DICER1, a key enzyme in microRNA synthesis. DICER1 conditional knockout animals are sterile and have uterine defects. We are currently in the process of characterizing the phenotype and the microRNA changes associated. Our goal is ultimately to identify which microRNAs are essential to uterine function. This work has been supported by American Society of Reproductive Medicine-National Institute of Child Health and Disease Reproductive Scientist Development Program (5K12HD000849-19), the Women's Reproductive Health Research Program (5K12HD050128) and the Specialized Cooperative Centers in Reproductive and Infertility Research (5U54HD07495).
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