School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom St, Liverpool, L3 3AF, UK.
Liverpool Centre for Cardiovascular Science, Liverpool John Moores University, Liverpool, UK.
J Mol Med (Berl). 2023 Feb;101(1-2):65-81. doi: 10.1007/s00109-022-02278-0. Epub 2022 Dec 20.
Prenatal diagnosis of congenital disease improves clinical outcomes; however, as many as 50% of congenital heart disease cases are missed by current ultrasound screening methods. This indicates a need for improved screening technology. Extracellular vesicles (EVs) have attracted enormous interest in recent years for their potential in diagnostics. EVs mediate endocrine signalling in health and disease and are known to regulate aspects of embryonic development. Here, we critically evaluate recent evidence suggesting that EVs released from the foetus are able to cross the placenta and enter the maternal circulation. Furthermore, EVs from the mother appear to be transported in the reverse direction, whilst the placenta itself acts as a source of EVs. Experimental work utilising rodent models employing either transgenically encoded reporters or application of fluorescent tracking dyes provide convincing evidence of foetal-maternal crosstalk. This is supported by clinical data demonstrating expression of placental-origin EVs in maternal blood, as well as limited evidence for the presence of foetal-origin EVs. Together, this work raises the possibility that foetal EVs present in maternal blood could be used for the diagnosis of congenital disease. We discuss the challenges faced by researchers in translating these basic science findings into a clinical non-invasive prenatal test.
先天性疾病的产前诊断可以改善临床结果；然而，目前的超声筛查方法仍有多达 50%的先天性心脏病漏诊。这表明需要改进筛查技术。近年来，细胞外囊泡（EVs）因其在诊断中的潜力而引起了极大的兴趣。EVs 在健康和疾病中介导内分泌信号，并已知调节胚胎发育的各个方面。在这里，我们批判性地评估了最近的证据，表明来自胎儿的 EV 能够穿过胎盘并进入母体循环。此外，似乎来自母亲的 EV 被反向运输，而胎盘本身则是 EV 的来源。利用转基因报告基因或荧光追踪染料的啮齿动物模型进行的实验工作提供了令人信服的证据，证明了胎儿-母体的串扰。这得到了临床数据的支持，这些数据表明胎盘来源的 EV 在母亲血液中表达，以及有限的证据表明存在胎儿来源的 EV。总的来说，这项工作提出了一种可能性，即存在于母亲血液中的胎儿 EV 可用于诊断先天性疾病。我们讨论了研究人员将这些基础科学发现转化为临床无创产前检测所面临的挑战。
