BeWo exomeres are enriched for bioactive extracellular placenta-specific C19MC miRNAs.

Area of Science:

• Cell Biology
• Extracellular Vesicles
• Molecular Biology

Background:

• Extracellular vesicles (EVs), including exosomes, are known carriers of extracellular microRNAs (miRNAs).
• Exomeres, a type of non-vesicular extracellular nanoparticle (NVEP), represent a novel class of extracellular cargo carriers.
• The characteristics and function of placental trophoblast-derived exomeres remain largely unexplored.

Purpose of the Study:

• To characterize trophoblast-derived exomeres.
• To investigate the cell-cell communication mediated by placenta-specific miRNAs carried by these exomeres.
• To compare exomeres with exosomes in terms of cargo and delivery efficiency.

Main Methods:

• Utilized an in vitro model system with BeWo trophoblasts and Jurkat T cells.
• Characterized BeWo exomeres and exosomes using nanoparticle analysis (size, morphology) and marker expression (AGO2, CD63, CD9, CD81, FLOT1, TSG101).
• Quantified placenta-specific miRNA levels and assessed miRNA delivery and target gene regulation (PRKG1) in recipient cells.

Main Results:

• BeWo exomeres exhibited distinct 'pilling-like' nanoparticle structures (∼40 nm), differing from cup-shaped exosomes (∼90-110 nm).
• BeWo cells secreted more exomeres than exosomes, with exomeres positive for AGO2 and negative for exosome markers.
• Exomeres showed significantly higher levels of placenta-specific miRNAs and delivered more miR-517a-3p to Jurkat cells compared to exosomes, leading to repression of PRKG1 expression.

Conclusions:

• Trophoblast-derived exomeres are distinct NVEPs enriched with bioactive, placenta-specific miRNAs.
• These exomeres efficiently deliver miRNAs for intercellular communication, impacting gene expression in recipient cells.
• Findings highlight the significant role of exomeres in placental biology, challenging the exclusive role of exosomes in carrying certain extracellular miRNA cargoes.