Table 2.
Updated Research Studies on EVs in PE Pathophysiology.
| EVs | Sample Type | Gestational Age | Isolation Method | Pregnancy Condition | Biological Process/Results | Reference |
|---|---|---|---|---|---|---|
| Maternal Blood Stream and other Body Fluids | ||||||
| Trophoblast derived exosomal micro RNA (has-miR-210) | Plasma and HTR-8 cell culture conditioned media | Third trimester | Membrane affinity spin column method | Normal and PE | This micro RNA is responsible for PE pathogenesis | [187] |
| Exosomes | Plasma | Third trimester (before cesarean section) | Commercial kit (ExoQuick) | Normal and PE | Vascular dysfunction | [194] |
| Exosomal micro RNAs | Placental mesenchymal stem cells culture conditioned media and peripheral blood | During cesarean section delivery | Ultracentrifugation followed by Real Time PCR | Normal Pregnancy (NP) and PE | High level of exosomal miRNA-136, 494, 495 in PE | [205] |
| Urinary Exosomal proteins | Urine | After 20 weeks | Centrifugation | Healthy non-pregnant, Normal pregnancy, PE | Phosphorylation of renal tubular sodium transporter proteins that enhance sodium reabsorption in PE compared to NP | [206] |
| Exosomes | Human umbilical cord mesenchymal stem cells (MSC) | After delivery | Flow cytometry based detection of MSC surface markers | PE | Effect on placental tissue morphology and angiogenesis in rat PE placenta | [207,208] |
| Placental syncytiotrophoblast derived extracellular vesicles (STBEVs) | Placental perfusate | Following cesarean section delivery | Centrifugation | Normal and PE pregnancy | Lower level of placental protein 13 was found in STBEVs of PE placenta | [195] |
| Placental extracellular vesicles | Cultured human placental villi explant and Maternal serum | First trimester placenta | Sequential centrifugation and ultracentrifugation | Normal pregnancy | Presence of antiphospholipid antibody increases the level of mitochondrial DNA in the placental EVs and increases the risk to develop PE | [196] |
| Microparticles | Maternal serum | 10–14 weeks | Centrifugation | Normal, PE, IUGR | Serum copeptin, annexin V were higher and placental growth factor was low in PE | [201] |
| Macovesicles/placental debris | Placental explant and maternal serum | First trimester (8–10 weeks) | Centrifugation | PE | Melatonin is secreted from placental explant that reduce PE sera induced production of endothelial cell activating placental EVs | [209] |
| Nanovesicles | Placenta | First trimester and term placenta | Differential centrifugation | PE | Transthyretin is increased in amount and incorporated in placental nanovesicles | [210] |
| EVs | Urine | Maternal urine | EVs were stained for annexin, nephrin and podocin proteins | PE and Normotensive pregnant women | Nephrin protein was packaged in increased amount in urinary EVs of PE women | [211] |
| Syncytiotrophoblast derived extracellular vesicles (STBEV) | Placental perfusion and maternal plasma | Gestational age matched | Differential centrifugation | Normal and PE | Less nitric oxide synthase in STBEVs of PE women | [202] |
| EVs | Placental explant | First and second trimester | Sequential centrifugation | Normal and PE | Endothelial dysfunction in severe early onset PE is via soluble angiogenic factors, not by EVs | [212] |
| Exosomes | Maternal plasma | First, second and third trimester | Differential centrifugation, ultracentrifugation followed by density gradient centrifugation | Normal and PE | The concentration of exosomes is higher and miRNA content is different in PE compared to normal pregnancy | [184] |
| Microparticles | Placental trophoblasts | At term (>37 weeks) | Two-step centrifugation | Uncomplicated and preeclamptic | Increase MP shedding from PE placenta; upregulation of caveolin-1 and downregulation of eNOS in these MPs which is modulated by vitamin-D | [213] |
| EVs | Endothelial cells and Platelets | Not mentioned | Differential centrifugation | Normal and PE | Inflammasome activation in placental trophoblasts results in PE development | [204] |
| Fetal Circulation | ||||||
| Exosomes | Umbilical cord blood | At delivery | Differential Centrifugation + Density gradient centrifugation | Normal | No difference in concentration of exosomes in term, small for gestational age, fetal growth restricted neonates | [198] |
| Microparticle (MPs) | Umbilical cord blood | At delivery | MPs were identified by size and annexin V fluorescein isothiocyanate (FITC) labelling | Normal and PE | MP levels is higher compared to maternal blood in PE | [199] |
| Exosomes | Umbilical cord blood | At delivery | Differential centrifugation + Filtration | Normal and PE | Altered protein expression profile that are involved with PE etiology | [200] |