Placenta-derived extracellular vesicles: their cargo and possible functions

Abstract

The literature on extracellular vesicles consists of rapidly expanding and often contradictory information. In this paper we attempt to review what is currently known regarding extracellular vesicles released specifically from human placental syncytiotrophoblast cells with a focus on the common but complex pregnancy-associated syndrome pre-eclampsia, where the level of syncytiotrophoblast extracellular vesicle release is significantly increased. We review common methods for syncytiotrophoblast extracellular vesicle derivation and isolation and we discuss the cargo of syncytiotrophoblast extracellular vesicles including proteins, RNA and lipids and their possible functions. A meta-analysis of available trophoblast-derived extracellular vesicle proteomic datasets revealed only three proteins in common: albumin, fibronectin-1 and plasminogen activator inhibitor-1, suggesting some variability in vesicle cargo, most likely reflecting stage and cell type of origin. We discuss the possible sources of variability that may have led to the low number of common markers, which has led us to speculate that markers and density in common use may not be strict criteria for identifying and isolating placenta-derived exosomes.

Isolation of human trophoblastic extracellular vesicles and characterization of their cargo and antiviral activity

“…It is also possible the EV cargo is influenced by disease state, as recently suggested in the context of preeclampsia [81–83], as well as the stage of pregnancy and the methodology used for analysis. [84]. Lastly, we note that EV subtypes might not be homogeneous [85].…”

Embryonic extracellular vesicles as informers to the immune cells at the maternal–fetal interface

“…In a metaanalysis published in 2017, Familari et al [57] summarizing the results of six different studies, showed that only three proteins were consistently found in all studies, namely albumin, fibronectin-1 (FN1) and plasminogen activator inhibitor-1 (PAI-1). In a metaanalysis published in 2017, Familari et al [57] summarizing the results of six different studies, showed that only three proteins were consistently found in all studies, namely albumin, fibronectin-1 (FN1) and plasminogen activator inhibitor-1 (PAI-1).…”

“…Several proteomic studies have investigated the composition of placenta-derived exosomes and MVs. In a metaanalysis published in 2017, Familari et al [57] summarizing the results of six different studies, showed that only three proteins were consistently found in all studies, namely albumin, fibronectin-1 (FN1) and plasminogen activator inhibitor-1 (PAI-1). The variability of the results obtained can be ascribed to differences in isolation techniques, placental age and to the interindividual genetic difference.…”

“…Deep sequencing analysis revealed that most RNAs are fewer than 500 nucleotides [60][61][62], the majority being miRNAs and then mRNAs. Corticotrophinreleasing hormone (CRH), hCG, placental alkaline phosphatase (PLAP) and human placental lactogen (HPL) mRNAs have been identified in trophoblast-derived EVs, but their functionality in vivo has yet to be confirmed [57,63,64].…”

Anoctamins/TMEM16 Proteins: Chloride Channels Flirting with Lipids and Extracellular Vesicles

“…It has become increasingly clear that EVs perform a fundamental role in intercellular communication by fusing with target cells to deliver microRNAs, lipid, and protein cargo. Recent investigation has demonstrated a role for EV signaling in many cell types including EV regulation of myogenesis in myoblasts, sperm maturation, osteoclast precursor differentiation, and may regulate trophoblast fusion, suggesting the signaling role of EVs is a general cellular phenomenon (62, 69, 87, 88). …”