甲状腺功能异常与妊娠期高血压疾病、子痫前期、胎儿生长受限、自发性流产等妊娠相关疾病的发生密切相关，但其具体机制尚未阐明。前期我们成功构建了甲状腺功能减退的自身免疫性甲状腺病小鼠模型，观察到模型小鼠流产率增加，出生子代体重降低；进一步通过免疫组织化学法发现胎盘部位蜕膜组织及动脉管腔内滋养细胞浸润减少，首次发现甲状腺素水平异常和胎盘血管重塑障碍相关。本课题拟通过临床研究观察妊娠不同时期甲亢/甲减对胎盘结构、子宫血流阻力等血管重塑指标的影响以及与妊娠相关疾病发生的相关性；拟建立滋养细胞血管内皮细胞三维共培养体系和ITGB3条件敲除小鼠模型，探索甲状腺素异常改变对血管内皮细胞、平滑肌细胞凋亡，滋养细胞浸润、迁徙和分化等血管重塑关键环节的影响，以及整合素αvβ3在此过程中的介导作用。甲状腺素/整合素αVβ3信号通路对胎盘血管重塑的调节机制将为妊娠相关疾病的发生提供创新机制和重要防治理论依据。

Thyroid dysfunction is the second most common endocrine disorder affecting females in reproductive age group. It has been known thyroid dysfunction is associated with increased risk of pregnancy hypertension, pre-eclampsia, intrauterine growth restriction and spontaneous abortion. However, the underlying mechanisms have not yet been elucidated. In our previous study, we found an increased rate of miscarriage in hypothyroidism mouse model. By immunohistochemistry analysis, we have found decreased invasion of trophoblasts into the decidua and vascular lumen. We found for the first time that the hypothyroidism may contribute to disorder in placenta vascular remodeling. Next, we plan to conduct a population-based cross section study, in order to elucidate the effect of thyroid dysfunction (either hyperthyroidism or hypothyroidism) on vascular remodeling in different stage of pregnancy. The ITGB3 mouse model and trophoblast-endothelial cells 3-D co-culture model will be set up to illuminates the role of integrin αvβ3 signaling pathway in the regulation of vascular remodeling. In this way, we are to elucidate the susceptibility and pathology mechanism of patients with thyroid dysfunction to pregnancy disorders. Such studies are important for both practical and theoretical fundation of the treatment of this kind of disease.