Table3_LC-MS/MS untargeted lipidomics uncovers placenta lipid signatures from intrahepatic cholestasis of pregnancy.xlsx

Aims: Intrahepatic cholestasis of pregnancy (ICP) stands as the predominant liver disorder affecting pregnant women, with a prevalence ranging from 0.2% to 15.6%. While ICP is known to heighten the chances of perinatal mortality and morbidity, its pathogenesis remains elusive, and therapeutic options are limited. The objective of this study was to explore the characteristic lipid signature in placentas collected from normal pregnancies and those with mild and severe intrahepatic cholestasis of pregnancy. This research aims to clarify the pathogenesis and identify lipid biomarker for ICP through LC-MS/MS based lipidomic analysis.
Methods and materials: Placenta samples were collected from 30 normal pregnancy women and 30 mild and severe ICP women respectively. Women with normal pregnancy and ICP were recruit from April 2021 to July 2022 in Chengdu, China. And LC-MS/MS based lipidomic analysis was used to explore the characteristic placental lipids in mild and severe ICP.
Results: Fourty-four lipids were differentially expressed both in mild and severe ICP placenta. The pathway analysis revealed these lipids are mainly enriched in glycerophospholipid metabolism and autophagy pathway. Weighted correlation network analysis (WGCNA) identified the correlation network module of lipids highly related to ICP. Using multiple logistic regression analysis, we identified three and four combined metabolites that had an area under receiver operating characteristic curves (AUC) ≥ 0.90.
Conclusion: Our results systematically revealed the lipid signature in mild and severe ICP placenta. The results may provide new insight into the treatment and early prediction of ICP.

研究目的：妊娠肝内胆汁淤积症（Intrahepatic cholestasis of pregnancy, ICP）是妊娠期女性最常见的肝脏疾病，患病率介于0.2%至15.6%之间。已知ICP会增加围产儿死亡与不良妊娠结局的发生风险，但其发病机制仍未阐明，且治疗手段有限。本研究旨在分析正常妊娠以及轻度、重度ICP孕妇的胎盘组织特征性脂质谱，通过基于液相色谱-串联质谱（LC-MS/MS）的脂质组学分析，阐明ICP的发病机制并筛选其脂质生物标志物。
材料与方法：本研究分别纳入30名正常妊娠孕妇与30名轻度、重度ICP孕妇，所有受试者均于2021年4月至2022年7月在中国成都入组。采集胎盘样本后，采用LC-MS/MS脂质组学技术分析轻度与重度ICP孕妇胎盘的特征性脂质表达谱。
研究结果：相较于正常妊娠胎盘，轻度与重度ICP孕妇的胎盘组织中共鉴定出44种差异表达脂质。通路富集分析显示，这些差异脂质主要富集于甘油磷脂代谢与自噬通路。加权基因共表达网络分析（Weighted correlation network analysis, WGCNA）鉴定出与ICP显著相关的脂质共表达模块。通过多因素logistic回归分析，本研究分别筛选出3种和4种组合代谢物，其受试者工作特征曲线下面积（AUC）均≥0.90。
研究结论：本研究系统揭示了轻度与重度ICP孕妇胎盘的特征性脂质谱，研究结果可为ICP的临床治疗与早期预测提供新的思路与理论依据。