Exosomes-Associated DNA—New Marker in Pregnancy Complications?

Abstract

Despite a large number of studies, the etiology of pregnancy complications remains unknown. The involvement of cell-free DNA or fetal cell-free DNA in the pathogenesis of pregnancy complications is currently being hypothesized. Cell-free DNA occurs in different forms—free; part of neutrophil extracellular traps; or as recently discovered, carried by extracellular vesicles. Cell-free DNA is believed to activate an inflammatory pathway, which could possibly cause pregnancy complications. It could be hypothesized that DNA in its free form could be easily degraded by nucleases to prevent the inflammatory activation. However, recently, there has been a growing interest in the role of exosomes, potential protectors of cell-free DNA, in pregnancy complications. Most of the interest from recent years is directed towards the micro RNA carried by exosomes. However, exosome-associated DNA in relation to pregnancy complications has not been truly studied yet. DNA, as an important cargo of exosomes, has been so far studied mostly in cancer research. This review collects all the known information on the topic of not only exosome-associated DNA but also some information on vesicles-associated DNA and the studies regarding the role of exosomes in pregnancy complications from recent years. It also suggests possible analysis of exosome-associated DNA in pregnancy from plasma and emphasizes the importance of such analysis for future investigations of pregnancy complications. A major obstacle to the advancement in this field is the proper uniformed technique for exosomes isolation. Similarly, the sensitivity of methods analyzing a small fraction of DNA, potentially fetal DNA, carried by exosomes is variable.

Tumor-Derived Exosomes in Immunosuppression and Immunotherapy

“…It is worth noting that Kawamura et al showed that a significant proportion of the detected mtDNA occurs on the surface of exosomes, but the significance of this location is unknown [43]. It has been suggested that this type of DNA may stimulate exosomal aggregation and possibly affect their function in recipient cells [44]. In turn, studies of exosomes released from glioblastoma and medulloblastoma cells under culture and in vivo conditions showed the presence of single-stranded DNA (ssDNA), referred to as exoDNA, including both genomic DNA (gDNA), complementary DNA, and transposonal DNA, probably derived from cytoplasmic and nuclear compartments.…”

A Protocol for Cancer-Related Mutation Detection on Exosomal DNA in Clinical Application

“…It is now increasingly clear that "exosomal" samples contain a heterogeneous mixture of small EVs. The methodology studies on exosomal DNA analysis still need some particular concerns (25), especially on the processes of exosome isolation and the subsequent DNA detection, etc. In this study, we took KRAS mutation detection in PC patients as an example, and compared the effects of some potential factors on the exosomal DNA analysis.…”

Inclusion Biogenesis, Methods of Isolation and Clinical Application of Human Cellular Exosomes

“…Thereby, exoDNA reflects the complete genomic DNA of the parental cell [66]. Other studies confirm these results suggesting that exosomes carry fetal cfDNA, that can be used as a biomarker for pregnancy complications [67]. On the contrary, study by Jeppesen et al contradicts feature of exosome as active vehicles for DNA release, suggesting that DNA is more likely released through endosomal mechanisms and autophagy [68].…”