Li Jianhua, Liu Qian, Liu Xuhui, Wang Yunyun, Jin Yuxia, Wang Weikai, Yi Bin, Wang Yanxia
Research center, Gansu Provincial Maternity and Child-Care Hospital (Gansu Provincial Central Hospital), Gansu, Lanzhou, China.
School of Public Health, Gansu University of Chinese Medicine, Lanzhou, China.
Int J Dev Biol. 2025;69(1):51-59. doi: 10.1387/ijdb.240170jl.
This study aims to analyze the pathways and the placental brain axis genes of gestational (GDM) affecting offspring neurodevelopment. Differentially expressed genes (DEGs) were identified through transcriptome sequencing of placental tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on DEGs. A protein-protein interaction (PPI) network was constructed and annotated using the STRING online software. The expression of neurodevelopment-related genes was analyzed by qPCR. Hubgenes were analyzed using Cytoscape 3.7.1 software. The correlation between Hubgenes and placental brain axis genes was analyzed through literatures alignment. The pathways of GDM affecting offspring neural development were predicted using the KEGG database. The placental transcriptome revealed that there were 404 DEGs between GDM and Normal groups. Among these DEGs, 125 were upregulated and 279 were downregulated. GO analysis indicated that DEGs were mainly involved in intracellular calcium activated chloride channel activity, anion channel activity, G protein-coupled peptide receptors, etc. Additionally, KEGG analysis revealed that DEGs were predominantly involved in neuroactive ligand receptor interaction pathways. STRING online software analysis revealed that the DLGAP1, NXNL2, SCG2, SLC18A2, LYNX1, GRM1, DLGAP1, BIRC7 genes were associated with neurodevelopment. PCR validation of these 8 genes was consistent with transcriptome results (<0.05). Literatures alignment showed that DLGAP1, GRM1 and SLC18A2 are placental brain axis genes that influence offspring neurodevelopment. The placental brain axis genes DLGAP1, GRM1, SLC18A2 have been found to influence GDM offspring neurodevelopment through the regulation of the Gq/PLC/PKC pathway.
本研究旨在分析妊娠期糖尿病（GDM）影响子代神经发育的途径及胎盘-脑轴基因。通过胎盘组织转录组测序鉴定差异表达基因（DEG）。对DEG进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析。使用STRING在线软件构建并注释蛋白质-蛋白质相互作用（PPI）网络。通过qPCR分析神经发育相关基因的表达。使用Cytoscape 3.7.1软件分析枢纽基因。通过文献比对分析枢纽基因与胎盘-脑轴基因之间的相关性。使用KEGG数据库预测GDM影响子代神经发育的途径。胎盘转录组显示，GDM组与正常组之间有404个DEG。在这些DEG中，125个上调，279个下调。GO分析表明，DEG主要参与细胞内钙激活氯离子通道活性、阴离子通道活性、G蛋白偶联肽受体等。此外，KEGG分析显示，DEG主要参与神经活性配体-受体相互作用途径。STRING在线软件分析显示，DLGAP1、NXNL2、SCG2、SLC18A2、LYNX1、GRM1、DLGAP1、BIRC7基因与神经发育相关。这8个基因的PCR验证结果与转录组结果一致（<0.05）。文献比对表明，DLGAP1、GRM1和SLC18A2是影响子代神经发育的胎盘-脑轴基因。已发现胎盘-脑轴基因DLGAP1、GRM1、SLC18A2通过调节Gq/PLC/PKC途径影响GDM子代的神经发育。
