Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio, United States of America.
Campus Chemical Instrument Center (CCIC), Mass Spectrometry and Proteomics Facility, The Ohio State University College of Medicine, Columbus, Ohio, United States of America.
PLoS One. 2022 Feb 25;17(2):e0262041. doi: 10.1371/journal.pone.0262041. eCollection 2022.
Fetal growth restriction (FGR) is associated with adverse perinatal outcomes. Pre-eclampsia (PreE) increases the associated perinatal morbidity and mortality. The structure of the umbilical cord in the setting of FGR and PreE is understudied. This study aimed to examine changes in the umbilical cord (UC) composition in pregnancies complicated by FGR and FGR with PreE. UC from gestational age-matched pregnancies with isolated FGR (n = 5), FGR+PreE (n = 5) and controls (n = 5) were collected, and a portion of the UC was processed for histologic and proteomic analysis. Manual segmentation analysis was performed to measure cross-section analysis of umbilical cord regions. Wharton's Jelly samples were analyzed on a tims-TOF Pro. Spectral count and ion abundance data were analyzed, creating an intersection dataset from multiple mass spectrometry search and inference engines. UCs from FGR and FGR with PreE had lower cross-sectional area and Wharton's Jelly area compared with control (p = 0.03). When comparing FGR to control, 28 proteins were significantly different in abundance analysis and 34 in spectral count analysis (p < 0.05). Differential expression analysis between PreE with FGR vs controls demonstrated that 48 proteins were significantly different in abundance and 5 in spectral count. The majority of changes occurred in proteins associated with extracellular matrix, cellular process, inflammatory, and angiogenesis pathways. The structure and composition of the UC is altered in pregnancies with FGR and FGR with PreE. Future work in validating these proteomic differences will enable identification of therapeutic targets for FGR and FGR with PreE.
胎儿生长受限（FGR）与围产儿不良结局相关。先兆子痫（PreE）增加了相关的围产儿发病率和死亡率。FGR 和 PreE 情况下脐带的结构尚未得到充分研究。本研究旨在研究 FGR 和 FGR 合并 PreE 妊娠中脐带（UC）成分的变化。收集了与单纯 FGR（n=5）、FGR+PreE（n=5）和对照组（n=5）相匹配的妊娠期 FGR 妊娠的一部分 UC，并进行了组织学和蛋白质组学分析。进行了手动分割分析以测量脐带区域的横截面分析。对 Wharton's Jelly 样本在 tims-TOF Pro 上进行了分析。对光谱计数和离子丰度数据进行了分析，从多个质谱搜索和推理引擎创建了一个交叉数据集。与对照组相比，FGR 和 FGR 合并 PreE 的 UC 横截面积和 Wharton's Jelly 面积较小（p=0.03）。与对照组相比，FGR 组在丰度分析中有 28 种蛋白质差异显著，在光谱计数分析中有 34 种蛋白质差异显著（p<0.05）。FGR 合并 PreE 与对照组相比，差异表达分析表明，在丰度和光谱计数方面，有 48 种蛋白质差异显著，有 5 种蛋白质差异显著。大多数变化发生在与细胞外基质、细胞过程、炎症和血管生成途径相关的蛋白质中。FGR 和 FGR 合并 PreE 妊娠中 UC 的结构和成分发生改变。未来对这些蛋白质组差异的验证工作将有助于鉴定 FGR 和 FGR 合并 PreE 的治疗靶点。
