Placental Tissue Exosome Research and Application

Placental tissue exosomes mediate the regulation of the maternal pregnancy environment, particularly based on intercellular communication that facilitates embryo implantation. Creative Biolabs provides research services on the placental tissue exosomes, providing clients with insights for exploring the causes of pregnancy complications and finding new biomarkers.

Features and Structure

Various placental component cells secrete placental exosomes, such as syncytial trophoblasts, cytotrophoblasts, extravillous trophoblasts, and placental vascular endothelial cells, among which syncytial trophoblasts covered with placental villi are the major producing ones. Placental alkaline phosphatase is located on the outer side of the exosome membrane and is a specific marker that distinguishes placental exosomes. Placental exosomes do not express classical MHC molecules outside the membrane, but rather express non-classical MHC-related molecules. It was also shown that the expression of HLA-G (human leukocyte antigen) was limited to the extravillous trophectoderm, which invades the maternal metaphase, while the syncytial trophectoderm was completely free of HLA-G. Exosomes originating from the syncytial trophectoderm do not activate NK cells due to the absence of HLA-G molecules. In addition to cytoskeletal proteins, vesicle transport proteins, macrophage inhibitory factors, and human cytomegalovirus protein UL16 binding proteins, the proteins located in the vesicles of placental exosomes express the pro-apoptotic molecules FasL and TRAIL, the endosomal sorting complex-associated protein Alix and the multivesicular vesicle protein TSG101, which are required for the transport of cellular regulatory factors (TGF-β and PD-L1). etc.

Fig.1 Placenta tissue extracellular vesicles. (Bai, 2021)

Involvement in Physiological Pregnancy

Placental exosomes maintain pregnancy by participating in vascular remodeling and down-regulating the immune response. On the one hand, vascular smooth muscle cell migration experiments have revealed that exosomes released from extravillous trophoblasts can participate in spiral artery remodeling by promoting vascular smooth muscle cell migration, which is required for the formation of low resistance circulation in the uteroplacental. The placental syncytial trophoblast cells derived exosomes were detected by real-time fluorescence quantitative PCR and ISH to release placenta-specific miRNAs into the maternal circulation. miR-155 could regulate vascular remodeling and its function. It contributes to the maintenance of pregnancy by providing good conditions. On the other hand, placental exosomes establish maternal-fetal immune tolerance by mediating the apoptosis of immune cells. It was found that syncytial trophoblast cells released exosomes carrying membrane bioactive FasL and TRAIL molecules, which inhibited the CD3-ζ chain and JAK3 and contributed to Th1 apoptosis. In addition, placental exosomes carry NKG2D ligands, which can downregulate NK cell activity by binding to receptors, thereby weakening maternal immune-killing toxicity.

Involvement in Pathological Pregnancy

Abnormal changes in the contents of placental exosomes can lead to placental dysfunction and cause many obstetric disorders such as preeclampsia and GDM (gestational diabetes mellitus). The increase in the number, level, and function of placental exosomes may lead to an imbalance in the maternal immune system, thus triggering eclampsia. Proteomic analysis revealed that the expression of functional proteins such as syncytium 2 protein, matrix metalloproteinase 2, and matrix metalloproteinase 9 in the placental exosomes of preeclampsia pathology were significantly different from that of normal pregnancy. GDM is one of the common metabolic disorders in pregnancy. Hyperglycemia, hyperinsulinemia, and hypoxia are the main pathological changes associated with it. These adverse internal environmental factors can adversely affect maternal-fetal blood flow exchange by affecting trophoblast exosomes, resulting in adverse pregnancy outcomes such as preterm delivery, fetal distress, and fetal death. Longitudinal assays observed higher concentrations of placental exosomes in the plasma of GDM patients than in normal pregnant women matched for gestational weeks. Meanwhile, miRNA sequencing revealed an increased abundance of miR-518a-5p, miR-518b, miR-518c, miR-518e, miR-520c-3p, and miR-525-525-5p in placental exosomes in GDM compared with normal women, which may serve as a predictive biomarker for GDM.

Fig.2 Placental exosomes in normal and pathologic pregnancies. (Jin & Menon, 2018)

The placenta secretes specific exosomes carrying a variety of signaling molecules, which are important mediators of intercellular communication between mother and fetus and embody various functions performed by the placenta. Placental exosomes establish an interactive dialogue between fetal and maternal cells and exert immunosuppressive effects through multiple mechanisms, which are closely related to the physiological and pathological processes of pregnancy. Creative Biolabs provides high-quality services for the characterization, histological profiling, and functional mechanisms of placental tissue exosomes. Please contact us to learn more.

References

Bai, K.; et al. Placenta-derived exosomes as a modulator in maternal immune tolerance during pregnancy. Front Immunol. 2021, 12: 671093.
Jin, J.; Menon, R. Placental exosomes: A proxy to understand pregnancy complications. Am J Reprod Immunol. 2018, 79(5): e12788.

Plant Exosome Isolation