Key Laboratory For Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, P.R. China.
Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, P.R. China.
Mol Med Rep. 2017 Nov;16(5):7405-7415. doi: 10.3892/mmr.2017.7507. Epub 2017 Sep 18.
Although monitoring and diagnosis of fetal diseases in utero remains a challenge, metabolomics may provide an additional tool to study the etiology and pathophysiology of fetal diseases at a functional level. In order to explore specific markers of fetal disease, metabolites were analyzed in two separate sets of experiments using amniotic fluid from fetuses with Down syndrome (DS) as a model. Both sets included 10‑15 pairs of controls and cases, and amniotic fluid samples were processed separately; metabolomic fingerprinting was then conducted using UPLC‑MS. Significantly altered metabolites involved in respective metabolic pathways were compared in the two experimental sets. In addition, significantly altered metabolic pathways were further compared with the genomic characters of the DS fetuses. The data suggested that metabolic profiles varied across different experiments, however alterations in the 4 metabolic pathways of the porphyrin metabolism, bile acid metabolism, hormone metabolism and amino acid metabolism, were validated for the two experimental sets. Significant changes in metabolites of coproporphyrin III, glycocholic acid, taurochenodeoxycholate, taurocholate, hydrocortisone, pregnenolone sulfate, L‑histidine, L‑arginine, L‑glutamate and L‑glutamine were further confirmed. Analysis of these metabolic alterations was linked to aberrant gene expression at chromosome 21 of the DS fetus. The decrease in coproporphyrin III in the DS fetus may portend abnormal erythropoiesis, and unbalanced glutamine‑glutamate concentration was observed to be closely associated with abnormal brain development in the DS fetus. Therefore, alterations in amniotic fluid metabolites may provide important clues to understanding the etiology of fetal disease and help to develop diagnostic testing for clinical applications.
尽管胎儿疾病的监测和诊断仍然具有挑战性，但代谢组学可能为在功能水平上研究胎儿疾病的病因和病理生理学提供另一种工具。为了探索胎儿疾病的特定标志物，我们使用唐氏综合征（DS）胎儿的羊水作为模型，在两个独立的实验中分析了代谢物。这两个实验集均包括 10-15 对对照和病例，并且单独处理羊水样本；然后使用 UPLC-MS 进行代谢组指纹图谱分析。比较了两个实验集中涉及各自代谢途径的差异代谢物。此外，还将显著改变的代谢途径与 DS 胎儿的基因组特征进行了进一步比较。数据表明，代谢谱在不同实验中存在差异，但是卟啉代谢、胆汁酸代谢、激素代谢和氨基酸代谢这 4 个代谢途径的改变在两个实验集中均得到了验证。共粪卟啉 III、甘氨胆酸、牛磺鹅脱氧胆酸、牛磺胆酸、氢化可的松、孕烯醇酮硫酸盐、L-组氨酸、L-精氨酸、L-谷氨酸和 L-谷氨酰胺的代谢物变化显著。进一步证实了这些代谢物的变化。对 DS 胎儿 21 号染色体上异常基因表达的分析表明，DS 胎儿中粪卟啉 III 的减少可能预示着异常的红细胞生成，而谷氨酰胺-谷氨酸浓度的失衡与 DS 胎儿异常的大脑发育密切相关。因此，羊水代谢物的改变可能为理解胎儿疾病的病因提供重要线索，并有助于开发用于临床应用的诊断测试。
