Placental exosomes: A proxy to understand pregnancy complications

Abstract

Exosomes (30- to 150-nm particles), originating from multivesicular bodies by the invagination of the endosomal membrane, are communication channels between cells. Exosomes are released by various cell types and cargo proteins, lipids, and nucleic acids reflecting the physiologic status of their cells of origin and cause functional changes in recipient cells, which are likely dependent on their quantity and/or cargo contents. Recently, placental exosomes, produced by various placental cell types, have been isolated from maternal blood using the placental protein-specific marker, placental alkaline phosphatase (PLAP). PLAP-positive exosomes are seen in maternal blood as early as the first trimester of pregnancy and increase as gestation progresses, with maximum numbers seen at term. Although the functional relevance of placental exosomes is still under investigation, several studies have linked placental exosomes changes (quantity and cargo) reflecting placental dysfunctions associated with adverse pregnancy events. As placental exosomes can be isolated from maternal blood, they are liquid biopsies reflecting placental functions. Hence, they are useful as biomarkers of placental functions and dysfunctions obtainable through non-invasive approaches. This review summarizes the biogenesis, release, and functions of exosomes and specifically expounds the role of placental-specific exosomes and their significance associated with pregnancy complications.

Extracellular vesicles generated by placental tissues ex vivo: A transport system for immune mediators and growth factors

“…To analyze EVs specifically from syncytiotrophoblasts (STB) of the explants, magnetic nanoparticles (MNPs) coupled to anti‐PLAP antibody, an antigen specific to STB, were used. EVs were labeled with BODIPY‐FL as described in Methods.…”

“…We found that STB‐specific EVs can be captured from placental villous culture supernatants using anti‐PLAP‐MNPs. PLAP is a sialoglycoprotein enzyme present almost exclusively on STBs and has been used as a marker of STB‐derived EVs . We first demonstrated specificity of capture by demonstrating that anti‐PLAP‐MNPs capture significant amounts of EVs from placental villous explants but very few EVs from culture supernatants of amnion explants.…”

Exosomal MicroRNAs in Pregnancy Provides Insight into a Possible Cure for Cancer

“…(1) Our study has identified novel exomiR in pregnancy which is linked to cancer biological processes such as immune evasion, migration and proliferation. (2) We propose that these specific targets can be used to engineer exosomes which target cancer cells to correct biological processes in preventing metastasis. (3) Preclinical trials which will involve testing in multiple in vivo models to assess efficacy in delivery and tumour cell reprogramming.…”

“…Recent interest in the bioactive properties of exosomes in the pathophysiology of complex diseases such as cancer [1], pregnancy complications [2] and HIV [3] has been at the forefront of research and development. Exosomes are classified as nanovesicles ranging from a size of 50 to 120 nm and are released from the cell via the lysosomal pathway.…”

“…Although the specific cellular molecular mechanisms in cancer and pregnancy are not completely understood, exosomes have been identified as a key constituent of the tumour and placental microenvironment (TME and PME). Their role in the TME and PME is to initiate and maintain multi-layered cellular communication directed towards cancer metastasis and trophoblast invasion during placental development, respectively [1,2].…”