单纯低甲状腺素血症(IMH)是最常见的妊娠甲状腺疾病之一，与妊娠期糖尿病、妊娠期高血压、早产的发生有关，而妊娠早期发生IMH会导致胎儿宫内生长受限和远期智力与运动水平的降低。近年来发现循环外泌体携带相关蛋白能够参与母体和胎儿细胞之间的持续交流，与妊娠相关疾病和胎儿发育不良有关，但具体作用机制不明。我们前期研究发现外周血sFlt-1的升高增加IMH的发生风险，并导致胎儿头臀长的降低和新生儿甲状腺功能减退，同时检测IMH孕妇外周血中外泌体，显示其sFlt-1蛋白含量明显增高。本研究将基于人群队列样本基础上，进一步通过体外实验，探索循环泌体携带sFlt-1蛋白对人甲状腺和胎盘微血管内皮细胞的损伤机制，并结合动物模型验证其对孕鼠甲状腺功能和胎鼠发育的影响。为阐明外泌体在参与母-胎对话和预防妊娠早期低甲状腺素血症的发生提供新思路，也为早期干预胎儿宫内生长受限及降低远期甲状腺功能受损风险提供理论依据。

Isolated maternal hypothyroxinemia (IMH) is one of the most common thyroid diseases in pregnancy, which is related to gestational diabetes, preeclampsia and preterm birth. IMH in early pregnancy will lead to intrauterine growth restriction and long-term decrease in intelligence and exercise level. In recent years, exosomes carrying proteins have been found to participate in the interaction between maternal and fetal cells, which is related to pregnant diseases and fetal development, but the specific mechanism is unknown. Our previous study found that the elevated sFlt-1 in peripheral blood increased the prevalence of IMH, and led to the decrease of crown rump length and newborn thyroid dysfunction. At the same time, exosomes in peripheral blood of IMH pregnant women were detected and the expression of sFlt-1 protein was significantly increased. Based on population cohort samples, this study will further explore the damage mechanism of sFlt-1 protein delivering by exosomes to human thyroid and placental microvascular endothelial cells in vitro experiments, and verify its effect on thyroid function and fetal development in mouse model. It provides a new perspective for exosomes to participate in maternal health and fetal development and prevent the occurrence of IMH in early pregnancy. It also provides a theoretical foundation for early intervention of fetal intrauterine growth restriction and reduction of thyroid dysfunction.