Proteomic analysis of the umbilical cord in fetal growth restriction and preeclampsia

• Published in: PloS one 2022-02, Vol.17 (2), p.e0262041-e0262041
• Main Authors: Conrad, Matthew S, Gardner, Miranda L, Miguel, Christine, Freitas, Michael A, Rood, Kara M, Ma'ayeh, Marwan
• Format: Article
• Language: English
• Subjects: Abundance; Acids; Adult; Analysis; Angiogenesis; Biology and Life Sciences; Blood Proteins - genetics; Cardiovascular disease; Care and treatment; Cellular structure; Childbirth & labor; College campuses; Composition; Cross-sections; Diagnosis; Electronic health records; Extracellular matrix; Extracellular Matrix Proteins - blood; Extracellular Matrix Proteins - genetics; Female; Fetal Growth Retardation - diagnostic imaging; Fetal Growth Retardation - genetics; Fetal Growth Retardation - metabolism; Fetal Growth Retardation - pathology; Fetus; Fetuses; Gestational Age; Growth; Gynecology; Health aspects; Humans; Inflammation; Mass spectrometry; Mass spectroscopy; Medical records; Medical schools; Medicine; Mesenchymal Stem Cells - metabolism; Methods; Morbidity; Morphology; Mortality; Obstetrics; Physical Sciences; Pre-eclampsia; Pre-Eclampsia - diagnostic imaging; Pre-Eclampsia - genetics; Pre-Eclampsia - metabolism; Pre-Eclampsia - pathology; Preeclampsia; Pregnancy; Proteins; Proteome - genetics; Proteome - metabolism; Proteomics; Research and Analysis Methods; Risk factors; Scientific imaging; Segmentation; Spectra; Statistical analysis; Structure; Therapeutic targets; Ultrasonic imaging; Ultrasonography, Prenatal; Umbilical cord; Umbilical Cord - metabolism; Veins & arteries
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0262041

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.