4.4 Article

Differences in cord blood extracellular vesicle cargo in preterm and term births

Journal

Publisher

WILEY
DOI: 10.1111/aji.13521

Keywords

biomarker; extracellular vesicles; preterm birth; umbilical cord

Funding

  1. NICHD [1R01HD084532-01A1]

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The study compared the proteomic profiles of cord plasma-derived exosomes in patients with spontaneous preterm birth (PTB) or preterm premature rupture of membranes (pPROM) to those who delivered at term, showing both similarities and unique markers in exosomes from different conditions. However, the inflammatory condition represented in exosomes from different conditions was found to be non-specific and not indicative of any specific underlying biological functions. The value of cord plasma exosome proteomic cargo as an indicator of underlying physiology or fetal well-being was deemed limited.
Objective This study determined the cord plasma-derived extracellular vesicle (exosomes; 30-160 nm particles) proteomic profile in patients who had spontaneous preterm birth (PTB) or preterm premature rupture of membranes (pPROM), compared to those who delivered at term regardless of labor status. Methods This is a cross-sectional analysis of a retrospective cohort that quantified and determined the proteomic cargo content of exosomes present in cord blood plasma samples in PTB or pPROM, and normal term in labor (TL) or term not in labor (TNIL) pregnancies. Exosomes were isolated by differential centrifugation followed by size exclusion chromatography. Exosomes were characterized by nanoparticle tracking analysis (quantity and size) and markers (dot blots for exosome markers). The exosomal proteomic profile was identified by liquid chromatography-mass spectrometry (LC-MS/MS). Ingenuity pathway analysis determined canonical pathways and biofunctions associated with dysregulated proteins. Results Cord plasma exosomes have similar quantity and exhibit both tetraspanin and ESCRT protein markers specific of exosomes regardless of the conditions. Proteomics analysis exhibited several similar markers as well as very unique markers in exosomes from each condition; however, bioinformatics analysis revealed a generalized and non-specific inflammatory condition represented in exosomes from different condition that is not indicative of any specific underlying biological functions indicative of an underlying pathology. Conclusions Compared to maternal plasma and amniotic fluid exosomes, the value of cord plasma derived exosomes is limited. Quantity, character, and proteomic cargo contents in exosomes or the pathways and functions represented by differentially expressed proteins do not distinguish specific conditions regarding normal and abnormal parturition. The value of cord plasma exosome proteomic cargo has limited value as an indicator of an underlying physiology or as a biomarker of fetal well-being.

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