妊娠肝内胆汁淤积症(ICP)足月前急性胎儿缺氧是围生儿死亡的重要原因，其机制不清。子宫胎盘胎儿单位缺氧应激血流调节是对抗孕晚期胎儿缺氧的重要机制。前期研究发现ICP胎盘应激激素促肾上腺皮质激素释放激素(CRH)和尿皮素(UCN) 呈低表达，提示可能与其组织细胞内质网应激异常有关。WFS1是调控未折叠蛋白反应(UPR)和内质网应激的重要基因，可能参与ICP胎盘应激激素表达调控。研究拟采用ICP孕鼠及其缺氧模型，通过过表达或沉默WFS1，观察胎盘WFS1、UPR信号通路、应激激素CRH/UCN和胎鼠急性缺氧指标的表达情况和一致性，了解WFS1通过调控UPR信号通路影响胎盘应激激素合成分泌、损害子宫胎盘胎儿单位血流应激调节、导致ICP胎鼠缺氧的可能机制。WFS1和UPR信号通路在子宫胎盘胎儿单位低氧缺氧应激血流调节中的作用尚未见文献报道，本研究可能为防治ICP急性胎儿缺氧提供新的临床方法。

The preterm acute fetal anoxia in intrahepatic cholestasis of pregnancy (ICP) is an important reason of perinatal mortality, which also results in high rates of iatrogenic preterm birth and cesarean delivery. The mechanism of acute fetal anoxia in ICP is unclear. Blood flow regulation of utero-placental-fetal unit in hypoxia stress is the most important mechanism in coping with fetal anoxia in late pregnancy. Previous studies indicated that the corticotropin-releasing hormone (CRH) and urocortin (UCN), the most potent concentration-dependent vasorelaxation factors, were down-regulated in placental tissues of ICP, indicated that the dysregulation of placental stress hormone is related to the dysfunction of endoplasmic reticulum stress in placental tissues and cells. WFS1 is a key gene in regulating the unfold protein response (UPR) and endoplasmic reticulum stress, which may also play a role in regulating the expression of placental stress hormone in ICP. This study use the intrahepatic cholestasis pregnant rat model and technical of gene over-expression/silence to observe the expression and consistency of placental WFS1, UPR-related signaling pathway, stress hormone (CRH/UCN) and fetal hypoxanthine (a factor of acute anoxia). Moreover, it is important to explore the underline mechanism of fetal anoxia, that is WFS1 interfere the synthesis and secretion of placental stress hormone via UPR signaling pathway, thus impair the blood flow stress regulation of utero-placental-fetal unit and lead to acute fetal anoxia. There is no literature about the role of WFS1 and UPR signaling pathway in utero-placental-fetal unit hypoxia stress compensatory and acute fetal anoxia mechanism of ICP. This study will provide new clinical method in preventing and treating acute fetal anoxia and even fetal death in ICP.