Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University in Bratislava, Bratislava 81108, Slovakia.
Institute of Physiology, Faculty of Medicine, Comenius University in Bratislava, Bratislava 81372, Slovakia.
Int J Mol Sci. 2019 Jun 13;20(12):2890. doi: 10.3390/ijms20122890.
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.
尽管有大量的研究,但妊娠并发症的病因仍不清楚。目前有人假设无细胞游离 DNA 或胎儿无细胞游离 DNA 参与妊娠并发症的发病机制。无细胞游离 DNA 以不同的形式存在——游离的;中性粒细胞细胞外陷阱的一部分;或者最近发现的,由细胞外囊泡携带。无细胞游离 DNA 被认为可以激活炎症途径,从而可能导致妊娠并发症。可以假设游离形式的 DNA 很容易被核酸酶降解,以防止炎症激活。然而,最近,人们对细胞外囊泡在妊娠并发症中的作用越来越感兴趣,细胞外囊泡是无细胞游离 DNA 的潜在保护者。近年来,人们的大部分兴趣都集中在细胞外囊泡携带的 microRNA 上。然而,与妊娠并发症相关的细胞外囊泡相关 DNA 尚未得到真正研究。作为细胞外囊泡的重要 cargo,DNA 迄今为止主要在癌症研究中进行了研究。这篇综述收集了关于细胞外囊泡相关 DNA 的所有已知信息,以及一些关于囊泡相关 DNA 的信息,以及近年来关于细胞外囊泡在妊娠并发症中作用的研究。它还提出了从血浆中分析细胞外囊泡相关 DNA 的可能方法,并强调了这种分析对未来妊娠并发症研究的重要性。该领域进展的一个主要障碍是细胞外囊泡分离的适当统一技术。同样,分析细胞外囊泡携带的一小部分 DNA(可能是胎儿 DNA)的方法的灵敏度也各不相同。