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Quantitative Proteomics by SWATH-MS of Maternal Plasma Exosome Determine Pathways Associated with Term and Preterm Birth

ABSTRACT: Maternal plasma (MP) samples were collected from group 1: term not-in labor (TNIL, n=13); group 2: term in labor (TL, n= 11), group 3: preterm premature rupture of membranes (pPROM, n=8); and group 4: preterm birth (PTB, n=13). Exosomes isolated from plasma by differential density centrifugation followed by size exclusion chromatography were characterised by morphology (electron microscopy), quantity and size (nanoparticle tracking analysis and markers (western blot). A quantitative, information-independent acquisition (Sequential Windowed Acquisition of All Theoretical Mass Spectra [SWATH]) approach was used to determine the protein profile in exosomes. Ingenuity Pathway Analysis (IPA) determined pathways associated with the protein profile identified in exosomes.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Ramkumar Menon

PROVIDER: MSV000083292 | MassIVE | Mon Dec 31 16:07:00 GMT 2018

SECONDARY ACCESSION(S): PXD012205

REPOSITORIES: MassIVE

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Project description:Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, precise phenotyping of the preterm birth is hampered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. The studyâ??s aim was to comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor using precisely phenotyped samples. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified the four groups of patients: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). The largest differences in gene expression among the four groups occurred in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5â?? and 3â??UTR regions. The results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection. 183 total RNA samples from 8 tissue types collected from 35 women grouped into six categories of pregnancy outcome. One microarray replicate per sample. Other Contributors: Radek Bukowski, Sam Parry and the NICHD Genomic and Proteomic Network for Preterm Birth Research

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Quantitative Proteomics by SWATH-MS of Maternal Plasma Exosome Determine Pathways Associated with Term and Preterm Birth

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