miR-518b靶向Egr-1调控胚胎早期发育机制的研究

临床上有近50%的自然流产病因不明,胚胎停育一直是生殖领域的研究热点。我们前期研究首次发现胚胎停育与滋养细胞中VEGF、可溶性受体 sFlt-1及调控血管生成的miR-518b有关,并证实Egr-1为miR-518b靶基因。根据这一发现及最新的研究成果,我们推测：miR-518b/Egr-1/VEGF信号通路参与孕早期胚胎发育调控,因此,本课题拟先在临床证实miR-518b在孕早期胚胎发育中的预测作用;然后构建妊娠缺氧大鼠模型,从动物实验验证miR-158b及Egr-1对孕早期绒毛血管增生的影响；再通过体外细胞实验，探讨缺氧状态下miR-518b的功能及对胚胎发育调控作用，通过上调和下调靶基因Egr-1，探讨miR-518b调控胚胎发育的路径。本课题从临床研究、动物实验和细胞实验逐步深入阐明miR-518b靶向Egr-1调控胚胎早期发育的机制，为防治胚胎停育提供理论依据及新的药物靶点。

Half of the causes of miscarriage are remain not clear. Early embryogenesis is an issue which gets a lot of attentionis in the field of reproductive these days.In our previous studies we found that embryo damage is related to proangiogenic factors VEG and its soluble receptor-1(SFlt-1) ,and also related to miR-518b which monitor the growing of vessels. Our further studies found that Egr-1 is a target gene of miR-518b. Therefore, we speculate that miR-518b/Egr-1/VEGF may regulates the development of embryo. In order to prove this point, it will be necessary to confirm the relevance between miR-518b/ Egr-1 and early embryogenesis. Then, it will be focused on verification of the role of the miR-518b and it’s target gene Egr-1 in early embryogenesis, especially the role of angiogenesis ability, in vivo and vitro with hypoxia. This studie tend to clarify the mechanism of how miR-518b and its target gene Egr-1 regulate the early embryogenesis. Therefore, the project might have theoretical significance and important implications for leading to potential therapeutic targets for the prevention of embryo damage.