Li Zhen, Cui Can, Li Jinping, Lai Guangrui, Qiao Chong
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Shenyang, Liaoning 110004, P.R. China.
Biomed Rep. 2025 Jul 25;23(4):159. doi: 10.3892/br.2025.2037. eCollection 2025 Oct.
Congenital heart disease (CHD) is the most common form of malformation seen in China. In most cases, its pathogenesis is unclear. The present study aimed to identify the differential metabolites and novel screening markers to discover the potential pathogenesis of CHD. Cultured amniotic fluid cells from pregnant patients carrying CHD-affected (n=24) or healthy (n=24) fetuses were collected. Untargeted metabolomics was performed on the cells. A total of 292 metabolites (172 up- and 120 downregulated) were significantly different between the CHD and control groups (variable importance on projection >1 and P<0.05). Significantly different metabolites were screened and analyzed using hierarchical clustering and Kyoto Encyclopedia of Genes and Genomes metabolic pathway enrichment. These data demonstrated that amino acid metabolism was considerable elevated. The most notable differential metabolites were lysine and arginine, suggesting they may play an important role in heart development. When arginine were used to treat pregnant mice, embryos (embryonic day 15.5) demonstrated increased malformation rate, the litter size decreased (4.3±1.03 vs. 6.5±1.05, P<0.01) and the naked deformity rate significantly increased (30.8 vs. 0.0%, P<0.001), compared with the controls. The embryonal heart cavity was larger and the heart wall became thinner. The present study suggested that amino acid metabolites may serve a crucial role in heart development and could serve as potential screening markers for CHD. Additionally, the adverse effects of arginine treatment on embryonic development highlight its role in CHD pathogenesis.
先天性心脏病（CHD）是中国最常见的畸形形式。在大多数情况下，其发病机制尚不清楚。本研究旨在鉴定差异代谢物和新型筛选标志物，以发现CHD的潜在发病机制。收集了携带CHD胎儿（n=24）或健康胎儿（n=24）的孕妇的培养羊水细胞。对这些细胞进行非靶向代谢组学分析。CHD组和对照组之间共有292种代谢物（172种上调和120种下调）存在显著差异（投影变量重要性>1且P<0.05）。使用层次聚类和京都基因与基因组百科全书代谢途径富集对显著差异的代谢物进行筛选和分析。这些数据表明氨基酸代谢显著升高。最显著的差异代谢物是赖氨酸和精氨酸，表明它们可能在心脏发育中起重要作用。当用精氨酸处理怀孕小鼠时，与对照组相比，胚胎（胚胎第15.5天）的畸形率增加，窝产仔数减少（4.3±1.03对6.5±1.05，P<0.01），裸畸形率显著增加（30.8%对0.0%，P<0.001）。胚胎心脏腔变大，心脏壁变薄。本研究表明氨基酸代谢物可能在心脏发育中起关键作用，并可作为CHD的潜在筛选标志物。此外，精氨酸处理对胚胎发育的不利影响突出了其在CHD发病机制中的作用。
