Protein profile changes in circulating placental extracellular vesicles in term and preterm births: a longitudinal study

Spontaneous preterm birth (PTB) is a major obstetrical problem around the globe and the mechanisms leading to PTB are unclear. Recently, changes in the circulating levels of placental extracellular vesicles (EVs) during pregnancy have been associated with various pregnancy complications. However, progress in the field is hindered by the inability to isolate placental EVs from the maternal circulation. A longitudinal study design was used to determine the protein cargo present in circulating placental EVs in maternal plasma of term and preterm birth across gestation (i.e. first, second and third trimester). Placental derived EVs were enriched from the total EVs population based on their expression of membrane bound placental alkaline phosphatase (PLAP). A quantitative, information-independent acquisition (Sequential Windowed Acquisition of All Theoretical Mass Spectra [SWATH]) approach identified and quantified the placental EV protein contents. PLAP+ EVs do not change in characteristics (size shape and markers) but did differ in numbers across gestation with low levels in PTB. A comparison analysis between the PLAP+ EV proteome from term and PTB revealed 96 proteins differing significantly (