Placenta-Derived Exosomes and Gestational Diabetes Mellitus

Figures & data

Figure 1 The functions and mechanisms of pdE in GDM. In gestational diabetes, hypoxia, high glucose, and BMI affect the production of placental exosomes, which in turn regulate insulin resistance, inflammatory factors, and endothelial cell dysfunction. These factors work together to promote the occurrence and development of diabetes and fetal growth and development.

Table 1 The Studies of Placental Exosomes in Gestational Diabetes Mellitus

Reference	Target	Tissue	Results
[92]	PLAP+ EVs	Plasma	Presence of high levels of placental exosomes in GDM
[106]	PLAP+ EVs	Placenta	Placental exosomes were associated with skeletal muscle insulin sensitivity
[107]	PLAP+ EVs	Placenta	PdE regulates glucose homeostasis
[111]	PLAP+ EVs	Placenta	STB-EVs from GDM perfused placentae show greater DPPIV activity
[125]	PLAP+ EVs	Placenta	ExGDM increased L-arginine transport, hCAT-1 and eNOS expression and activity, and p44/42mapk activation
[140]	PLAP+ EVs	Plasma	Placental-derived exosomes increased ∼2.1-fold in GDM compared to normal through gestation
[116]	miR-494	Placenta	MiR-494 downregulated
[118]	miR-6869-5p	Placenta	MiR-6869-5p promoted M2 macrophage polarization and thus restrain inflammation
[122]	miR-518d	Placenta	MiR-518d was higher in the placenta of GDM and was negatively correlated with the levels of PPARα protein
[123]	miR-518d	Placenta	MiR-518d negatively regulates the expression of PPARα and triggers the nuclear transport process of NF-κB
[152]	miR-516-5p, miR-517-3p, miR-518-5p, miR-222-3p, miR-16-5p	Urinary	All the miRNAs examined were downregulated in patients with GDM
[33]	miR-508-3p, miR-27a, miR-9, miR-137, miR-92a, miR-33a, miR-30d, miR-362-5p, miR-502-5p	Placenta	29 differently expressed miRNA in the array, 9 replicated by qPCR.miR-508-3p upregulated and the rest, down-regulated
[150]	miR-223, miR-23a	Serum	AUC 0.91, sensitivity of 90%, specificity of 94%
[115]	mir-143	Placenta	50% reduction in A2GDM (controlled by medication) but not A1GDM(controlled by diet)
[110]	miR-140	Placenta	MiR-140-3p overexpression contributes to the defective placental IR signaling in patients with GDM
[148]	miR-132, miR-29a, miR-222	Serum	The expression levels of three miRNAs were significantly decreased in GDM women
[147]	miR-126-3p, miR-155-5p, miR-21-3p, miR-146b-5p, miR-210-3p, miR-222-3p, miR-223-3p, miR-517-5p, miR-518a-3p, miR-29a-3p	Plasma	Circulating early-mid-pregnancy miRNAs are associated with GDM, particularly among women who are overweight/obese pre-pregnancy or pregnant with male offspring
[143]	miR-16-5p, miR-17-5p, miR-20a-5p	Plasma	AUC 0.92, 0.88, and 0.74 sensitivity 41.6%, 21.4% and 17.8% specificity 95.8%, 95.4% and 95.4%
[127]	miR-101	Umbilical cord vein	GDM impairs HUVEC function via miR-101 upregulation
[119]	hsa-miR-371a-5p, hsa-miR-374b-5p, hsa-miR-609, hsa-miR-875-5; hsa-miR-365a-3p, hsa-miR-146b-3p, hsa-miR-568; hsa-miR-574-3p, hsa-miR-325, hsa-miR-520e, hsa-miR-145-5p, hsa-miR-583	Plasma	MiRNAs are mostly up-regulated and hsa-miR-145-5p and hsa-miR-875-5p targets the most genes
[149]	miR-16-5p, miR-29a-3p, miR-134-5p	Serum	AUC 0.687, sensitivity of 72.5%, specificity of 57.5%
[114]	miR-657	Placenta	Dysregulation of miR-657 contributes to the pathogenesis of GDM via IL-37/NF-κB signaling axis
[108]	miR-409-5p	Serum	MiR-409-5p is highly expressed in the serum of patients with GDM, and it is positively correlated with the insulin resistance index
[109]	miR-185	Serum placenta	The down-regulation of miR-185 expression in serum and placenta of pregnant women with GDM is negatively correlated with HOMA-IR
[105]	miRNA profiles	Serum	Ten miRNAs showed significantly higher levels
[145]	miRNA profiles	Serum	Total of 32 miRNAs, 12 were significantly upregulated and 20 were significantly downregulated in GDM
[103]	miRNAs lncRNAs	Umbilical cord blood	84 mRNAs and 256 lncRNAs as differentially expressed
[139]	lncRNA profiles	Umbilical cord vein	Total of 8814 lncRNAs, 349 were significantly upregulated and 892 were significantly downregulated in GDM
[104]	Circular RNA profiling	Placenta	Total of 48,270 circRNAs, 227 were upregulated and 255 down-regulated
[102]	Circular RNA profiling	Umbilical cord blood	Total of 88,371 circRNAs. 229 circRNAs were up-regulated and 278 circRNAs were down-regulated
[151]	Cell-free DNA	Serum	CfpDNA multiples of the median (MoMs) were lower in women who later developed GDM

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