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. 2020 Mar 16;24(8):4377–4388. doi: 10.1111/jcmm.15144

Table 1.

The clinical values of EVs in pregnancy complications

Pregnancy complications Source of EVs Pregnancy stage Targets Isolation method Detection method Clinical value References
Pre‐eclampsia Plasma Early Total exosomes, exosomal PLAP Ultracentrifugation, differential centrifugation ELISA Elevated in PE at early pregnancy (AUC 0.745 and 0.829) 85
Plasma Late Exosomal PLAP to total exosomes ratio Ultracentrifugation ELISA Reduced in PE; lower in late‐onset PE than early‐onset PE 86
Plasma Late miRNAs profile Commercial kit Nanostring counter system miRNA assay Potential markers of PE and subtypes of PE 88
Plasma Mid and late miR‐210 Commercial kit qRT‐PCR Elevated in PE; higher in severe PE 89
Plasma Early miR‐486‐1‐5p, miR‐486‐2‐5p Ultracentrifugation, differential centrifugation RNA sequencing Elevated in PE at early pregnancy 85
Plasma Mid and late miR‐136, miR‐494, miR‐495 Ultracentrifugation qRT‐PCR 6.4‐, 3.9‐ and 2.1‐fold higher in PE than normal pregnancy 91
Serum Late miR‐155 Ultracentrifugation, differential centrifugation qRT‐PCR Elevated in PE 81
Serum Late miR‐548c‐5p Commercial kit qRT‐PCR Reduced in PE 65
Plasma Early miR‐517‐5p, miR‐520a‐5p, miR‐525‐5p Commercial kit qRT‐PCR Reduced in PE at early pregnancy (AUC 0.719) 92
Plasma Late PLAP+NEP+ EVs Size exclusion chromatography FCM Elevated in PE 82
Urine Late Podocin+ EVs‐to‐nephrin+ EVs ratio Without isolation FCM Elevated in PE; correlated with renal injury 94
Urine Late ENaC, NKCC2 Differential centrifugation WB Elevated in PE; correlated with renal injury 96
Gestational diabetes mellitus Plasma Early, mid and late PLAP+EVs Ultracentrifugation, differential centrifugation ELISA 2.2‐fold higher at early gestation in GDM than normal pregnancy 66
Plasma Early, mid and late PLAP per exosome Ultracentrifugation, differential centrifugation ELISA 63% lower at early gestation in GDM than normal pregnancy 66
Oral fluid Early Total exosomes Commercial kit NTA Elevated in GDM at early pregnancy (AUC 0.81) 97
Plasma Late miR‐125a‐3p, miR‐99b‐5p, miR‐197‐3p, miR‐22‐3p, miR‐224‐5p Ultracentrifugation, differential centrifugation RNA sequencing, qRT‐PCR Elevated in GDM; related to metabolism 45
Serum Early 10 miRNAs Differential centrifugation qRT‐PCR Elevated in GDM at early pregnancy 98
Plasma Late DPPIV+PLAP+ EVs Without isolation FCM Eightfold higher in GDM than normal pregnancy 99
Plasma Late 78 proteins Ultracentrifugation SWATH‐MS Potential markers of GDM 100
Preterm birth Plasma Early, mid and late 173 miRNAs Ultracentrifugation RNA sequencing Potential markers of PTB 103
Urine Late 16S rRNAs derived from Ureaplasma and Veillonellaceae Differential centrifugation RNA sequencing Elevated in PTB 104
Plasma Late 72 proteins Differential centrifugation, size exclusion chromatography SWATH‐MS Potential markers of PTB 69
Plasma Early 62 proteins Size exclusion chromatography LC‐MS PTB predictor at early pregnancy 105
Foetal growth restriction Plasma Late PLAP+ exosomes to total exosomes ratio Ultracentrifugation, differential centrifugation NTA Reduced in FGR; corrected with birth weight percentile 106
Serum Mid miR‐20b‐5p, miR‐942‐5p, miR‐324‐3p, miR‐223‐5p, miR‐127‐3p RNA sequencing Elevated in FGR 107

Abbreviations: ELISA, enzyme‐linked immunosorbent assay; FCM, flow cytometry; LC‐MS, liquid chromatograph‐mass spectrometer; NTA, nanoparticle tracking analysis; qRT‐PCR, quantitative polymerase chain reaction; SWATH‐MS, sequential windowed acquisition of all theoretical mass spectra; WB, Western blotting.