Department of Obstetrics and Gynecology, University of Texas Houston Health Sciences, Houston, Texas.
Shriners Pediatric Research Center, Center for Neural Repair and Rehabilitation, Temple University, Philadelphia, Pennsylvania.
Prenat Diagn. 2019 Jul;39(8):609-615. doi: 10.1002/pd.5474. Epub 2019 Jun 13.
We have developed novel methods for isolating fetal central nervous system (CNS)-derived extracellular vesicles (FCEs) from maternal plasma as a non-invasive platform for testing aspects of fetal neurodevelopment in early pregnancy. We investigate the hypothesis that levels of defined sets of functional proteins in FCEs can be used to detect abnormalities in fetal neuronal and glial proliferation, differentiation, and survival.
Maternal plasma was obtained between 10 and 19 weeks from women with current heavy EtOH exposure and matched controls. FCE levels of synaptophysin, synaptotagmin, synaptopodin, and neurogranin were quantified normalized to the exosome marker CD81. Quantitative RT-PCR was performed with specific primers for miR-9.
FCE cargo protein levels of synaptophysin, synaptotagmin, synaptopodin, and neurogranin were all significantly reduced in pregnancies exposed to current heavy EtOH use (P < .001 for all). Both synaptophysin and neurogranin appeared to be particularly discriminatory with no overlap between exposed and control subjects. Up to tenfold inhibition (90%) in MicroRNA-9 was observed in FCEs from EtOH exposed fetuses compared with controls.
Our results suggest that FCEs purified from maternal plasma may be a powerful tool to assess abnormal proliferation and differentiation of CNS stem cells as early as the late first trimester. What's already known about this topic? Exosomes/extracellular vesicles (ECVs) are emerging as exciting novel biomarkers in neurologic disease (Alzheimers) What does this study add? Evidence that Fetal CNS ECVs can be isolated from maternal blood The origin of the ECVs appears to be the fetal brain and not the placenta Findings with ECVs correlates with fetal exposure to alcohol. Potential for first trimester prenatal diagnosis of fetal neurologic disease.
我们开发了从母体血浆中分离胎儿中枢神经系统（CNS）衍生的细胞外囊泡（FCE）的新方法，作为检测早孕胎儿神经发育各个方面的非侵入性平台。我们假设，FCE 中特定功能蛋白的水平可用于检测胎儿神经元和神经胶质增殖、分化和存活的异常。
在妊娠 10-19 周时，从当前大量饮酒的女性和匹配的对照组中获得母体血浆。用外泌体标志物 CD81 对突触小体蛋白、突触结合蛋白、突触小泡蛋白和神经颗粒蛋白的 FCE 水平进行定量。用特定的 miR-9 引物进行定量 RT-PCR。
当前大量饮酒暴露的妊娠中，FCE 货物蛋白水平的突触小体蛋白、突触结合蛋白、突触小泡蛋白和神经颗粒蛋白均显著降低（均 P <.001）。突触小体蛋白和神经颗粒蛋白似乎具有特别的鉴别能力，暴露组和对照组之间没有重叠。与对照组相比，FCE 中 MicroRNA-9 的抑制率高达 10 倍（90%）。
我们的结果表明，从母体血浆中纯化的 FCE 可能是一种强大的工具，可用于评估早孕晚期中枢神经系统干细胞的异常增殖和分化。
外泌体/细胞外囊泡（ECV）作为神经疾病（阿尔茨海默病）的新型有前途的生物标志物正在出现。
证据表明，胎儿中枢神经系统 ECV 可从母体血液中分离出来。
ECV 的起源似乎是胎儿大脑，而不是胎盘。
与胎儿接触酒精的发现相关。
有可能在早孕时进行胎儿神经疾病的产前诊断。
