TRIP10 as a Key Regulator in Fetal Growth Restriction: a Study Integrating Bioinformatics Screening with Experimental Validation.

Fetal growth restriction (FGR) is a leading cause of perinatal mortality, yet its molecular mechanisms remain poorly understood. This study integrated bioinformatic analysis with experimental validation to identify key genes involved in FGR pathogenesis. Transcriptome datasets GSE114691 and GSE24129 from the GEO database were analyzed, revealing 5,788 differentially expressed genes (1,450 upregulated, 4,338 downregulated) between FGR and control placental samples. Functional enrichment analysis indicated that downregulated genes were primarily involved in mitochondrial function, aerobic respiration, and amino acid metabolism, while upregulated genes were associated with cell adhesion and histone modification. Weighted gene co-expression network analysis (WGCNA) identified 19 modules, with the darkorange module showing the strongest positive correlation with FGR. LASSO regression further selected eight candidate genes, among which only TRIP10 demonstrated consistent and significant upregulation in the independent validation dataset and exhibited excellent diagnostic performance (AUC = 0.906). Western blot confirmed significant upregulation of TRIP10 protein in FGR placental tissues. Functional assays in JEG-3 trophoblast cells revealed that TRIP10 knockdown significantly enhanced cell migration and invasion, while TRIP10 overexpression suppressed these processes. Collectively, this study identifies TRIP10 as a key gene significantly upregulated in FGR placentas and establishes TRIP10 as a negative regulator of trophoblast migration and invasion, suggesting that TRIP10 dysregulation may contribute to impaired placental development and FGR pathogenesis, representing a promising biomarker and potential therapeutic target.