Center for Neural Repair and Rehabilitation (Shriners Hospitals Pediatric Research Center), Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.
Int J Mol Sci. 2024 May 27;25(11):5826. doi: 10.3390/ijms25115826.
Fetal alcohol spectrum disorders (FASDs) are leading causes of neurodevelopmental disability but cannot be diagnosed early in utero. Because several microRNAs (miRNAs) are implicated in other neurological and neurodevelopmental disorders, the effects of EtOH exposure on the expression of these miRNAs and their target genes and pathways were assessed. In women who drank alcohol (EtOH) during pregnancy and non-drinking controls, matched individually for fetal sex and gestational age, the levels of miRNAs in fetal brain-derived exosomes (FB-Es) isolated from the mothers' serum correlated well with the contents of the corresponding fetal brain tissues obtained after voluntary pregnancy termination. In six EtOH-exposed cases and six matched controls, the levels of fetal brain and maternal serum miRNAs were quantified on the array by qRT-PCR. In FB-Es from 10 EtOH-exposed cases and 10 controls, selected miRNAs were quantified by ddPCR. Protein levels were quantified by ELISA. There were significant EtOH-associated reductions in the expression of several miRNAs, including miR-9 and its downstream neuronal targets BDNF, REST, Synapsin, and Sonic hedgehog. In 20 paired cases, reductions in FB-E miR-9 levels correlated strongly with reductions in fetal eye diameter, a prominent feature of FASDs. Thus, FB-E miR-9 levels might serve as a biomarker to predict FASDs in at-risk fetuses.
胎儿酒精谱系障碍（FASD）是导致神经发育障碍的主要原因，但无法在子宫内早期诊断。由于几种 microRNA（miRNA）与其他神经和神经发育障碍有关，因此评估了 EtOH 暴露对这些 miRNA 及其靶基因和途径表达的影响。在怀孕期间饮酒（EtOH）的女性和不饮酒的对照组中，按胎儿性别和胎龄个体匹配，从母亲血清中分离出的胎儿脑源性外泌体（FB-Es）中的 miRNA 水平与自愿终止妊娠后获得的相应胎儿脑组织含量密切相关。在 6 例 EtOH 暴露病例和 6 例匹配对照中，通过 qRT-PCR 在阵列上定量了胎儿脑和母血清 miRNA 的水平。在 10 例 EtOH 暴露病例和 10 例对照的 FB-Es 中，通过 ddPCR 定量了选定的 miRNA。通过 ELISA 定量了蛋白质水平。几种 miRNA 的表达与 EtOH 显著相关，包括 miR-9 及其下游神经元靶标 BDNF、REST、Synapsin 和 Sonic hedgehog。在 20 对病例中，FB-E miR-9 水平的降低与胎儿眼睛直径的降低密切相关，这是 FASD 的一个显著特征。因此，FB-E miR-9 水平可能作为预测高危胎儿 FASD 的生物标志物。
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