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

Abstract

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.

Human cord plasma proteomic analysis reveals sexually dimorphic proteins associated with intrauterine growth restriction

“…However, other biological processes, such as electron transport chain and nucleotide metabolic and catabolic processes were also enriched, while the pro-teins the lowest fold change in IUGR versus AGA were predominantly involved in platelet degranulation and aggregation, cell adhesion and regulation of response to stimulus. These findings agree with previous studies that identified platelet activation and extracellular matrix remodeling in fetal growth restriction [21].…”

“…Several proteins identified in our cohort (e.g., CAT, HBG1, PKM, PNP, S100A8, IDH1) were previously reported to be associated with fetal growth restriction using either maternal or cord plasma [12,15,21]. IUGR is associated with impaired nutrient and/or oxygen delivery that may leave the mononuclear cells in cord plasma, fetal organs and placenta more susceptible to damage and leakage of cytosolic proteins consistent with the increased levels of proteins such as CAT in IUGR cord plasma [12,15,24,25].…”

Umbilical Cord Diseases Affecting Obstetric and Perinatal Outcomes

“…Maternal diseases such as preeclampsia (PE) may be associated with fetal growth restriction (FGR), in turn resulting in a higher risk of adverse obstetric and perinatal outcomes such as stillbirths or long-term morbidity [8][9][10]. A recent proteomic investigation demonstrated that in fetuses with FGR or PE with superimposed FGR, the most significant changes occurring to the umbilical cord involved proteins associated with Wharton's jelly and inflammatory and angiovascular processes [11].…”

Placental proteome in late‑onset of fetal growth restriction

“…One of the promising diagnostic methods is comparative proteomics based on the analysis of the protein profile in normal and abnormal tissues (29). Reviews have highlighted the proteomic approaches that have been used to explore pre-eclampsia (PE), FGR and preterm birth (30)(31)(32)(33)(34).…”