单合子双胎具有相同的DNA序列及宫内环境，选择性宫内生长受限（sIUGR）是此类双胎常见的严重并发症，其发病的分子机制未明。我们已证实sIUGR双胎中，生长受限胎所属胎盘份额小、胎盘血管密度及分支减少。前期通过测序技术发现小胎胎盘中miR210表达显著高于大胎。胎盘miR210差异表达与sIUGR发病的关系及其机制是什么？在细胞缺氧模型中我们发现HIF-1α诱导miR210上调，其预测的靶基因THSD7A在胎盘滋养细胞表达丰富。推测THSD7A可能与滋养细胞侵袭增殖、血管形成相关。据此假设：双胎之一胎对应的胎盘局部缺氧时HIF-1α调控miR210表达升高，继而使THSD7A下调，影响滋养细胞功能，造成胎盘绒毛和血管发育障碍，导致一胎发育滞后从而发生sIUGR。本项目拟探讨胎盘HIF-1α调控miR210/THSD7A在sIUGR发病中的作用机制，进一步为胎盘源性疾病的防治提供科学依据。

The DNA sequence and intrauterine environment between zygotic twins are almost the same. Selective intrauterine growth restriction (sIUGR) is one of the most severe complications among zygotic twins with adverse outcome, but the mechanism of which is still unclear. We have found that the smaller twin of sIUGR shared less placenta and had sparser vasculature compared with the larger twin. Our previous study in which we investigated the different expressions of miRNA in the placenta of sIUGR showed that miR210 was much higher expressed in the placenta of the small fetuses than that of the lager ones. We infer that the different expressions of miR210 play an important role in sIUGR，but what is the mechanism in this process? Our further study showed that miR210 is induced by hypoxia induced factor 1α (HIF-1α) under a circumstance of hypoxia. We have demonstrated that THSD7A, one of the predicted target genes of miR210, was expressed abundantly in placenta. Previous studies had showed that THSD7A may have an impact on the development of trophoblasts and vasculature. Thus, we presume that the up-regulation of miR210 induced by HIF-1α inhibits the expression of THSD7A, leading to the dysplasias of trophoblasts and vasculature. The dysfunction of placenta results in sIUGR. The purpose of this project is to investigate the mechanism of miR210 and THSD7A regulated by HIF-1α in placenta of sIUGR and try to provide a new insight for the pathogenesis and prenatal treatment of complicated twins and placenta-derived diseases.