Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Sichuan, 610041, China.
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Sichuan, 610041, China.
Placenta. 2019 Aug;83:63-71. doi: 10.1016/j.placenta.2019.06.378. Epub 2019 Jun 22.
The most adverse perinatal outcome of intrahepatic cholestasis of pregnancy (ICP) is sudden fetal death related to acute fetoplacental hypoxia. Corticotrophin-releasing hormone (CRH), urocortin (UCN), and Wolfram syndrome 1 (WFS1) proteins may have a compensatory response to hypoxic stress.
A total of 108 singleton pregnant women were divided into three groups: control, late-onset ICP, and early-onset ICP. Enzyme-linked immunosorbent assays were used to detected maternal serum CRH, UCN, and WFS1 levels. Western blotting and real-time polymerase chain reaction were conducted to quantify placental protein and mRNA levels of CRH, UCN, and WFS1. Pearson correlation scatterplots and Pearson correlation matrix were employed to testify the correlation.
Placental WFS1 had a positive relation with placental UCN (r = 0.69, P < 0.05) and serum UCN (r = 0.36, P < 0.05). Placental CRH was positively correlated with maternal serum CRH (r = 0.53, P < 0.05). Maternal serum and placental levels of CRH, UCN, and WFS1 significantly increased in the early-onset ICP group compared with the control group (P < 0.05). Placental levels of UCN and WFS1 in the early-onset ICP group were significantly elevated and higher in comparison with the late-onset ICP group (P < 0.05). However, the transcriptional levels of CRH, UCN, and WFS1 were impaired in the early-onset ICP group.
Our study revealed that transcription and translation of WFS1, CRH, and UCN were altered during pregnancies complicated by early-onset ICP. This disrupted compensatory response mediated by WFS1 and CRH family peptides in early-onset ICP may play a significant role in the pathogenesis of sudden fetal death in acute fetal hypoxia.
妊娠肝内胆汁淤积症（ICP）最不利的围产期结局是与急性胎-胎盘缺氧相关的突发胎儿死亡。促肾上腺皮质激素释放激素（CRH）、孤啡肽（UCN）和沃尔夫拉综合征 1 型（WFS1）蛋白可能对缺氧应激有代偿反应。
共纳入 108 例单胎孕妇，分为三组：对照组、晚发型 ICP 组和早发型 ICP 组。采用酶联免疫吸附试验检测母血清 CRH、UCN 和 WFS1 水平。采用 Western blot 和实时聚合酶链反应检测 CRH、UCN 和 WFS1 的胎盘蛋白和 mRNA 水平。采用 Pearson 相关散点图和 Pearson 相关矩阵检验相关性。
胎盘 WFS1 与胎盘 UCN（r=0.69，P<0.05）和血清 UCN（r=0.36，P<0.05）呈正相关。胎盘 CRH 与母血清 CRH 呈正相关（r=0.53，P<0.05）。与对照组相比，早发型 ICP 组母血清和胎盘 CRH、UCN 和 WFS1 水平显著升高（P<0.05）。早发型 ICP 组 UCN 和 WFS1 水平明显升高，高于晚发型 ICP 组（P<0.05）。然而，早发型 ICP 组 CRH、UCN 和 WFS1 的转录水平受损。
本研究表明，早发型 ICP 妊娠时 WFS1、CRH 和 UCN 的转录和翻译发生改变。早发型 ICP 中由 WFS1 和 CRH 家族肽介导的代偿反应受损，可能在急性胎儿缺氧导致的突发胎儿死亡发病机制中起重要作用。
