Discovery and validation of key genes and potential mechanisms linked to endothelial cell senescence and carbohydrate metabolism in recurrent spontaneous abortion.

Objectives: Recurrent spontaneous abortion (RSA) is a major pregnancy complication with largely unknown causes. Carbohydrate metabolism (CM) disorders can affect the progression of endothelial cell senescence (ES), thereby leading to placental dysfunction. However, research on the interplay between CM and ES in RSA is limited. This study aims to identify key genes at the intersection of CM- and ES-related pathways in RSA via various bioinformatics methods. Methods: Datasets GSE165004 (training) and GSE26787 (validation) were downloaded from the GEO database. ES- and CM-related genes were obtained from previous literature. Key genes were obtained through WGCNA, two machine learning algorithms, gene expression analysis in the training and validation datasets, and RT-qPCR analysis. A comprehensive evaluation was conducted to assess the diagnostic potential of key genes. Results: Two genes (BDH1, PIK3C2G) were recognized as key genes in RSA, which were upregulated in RSA. Immune infiltration analysis revealed that the key genes were negatively correlated with three distinct immune cell types. Both genes are linked to the cytokine-cytokine receptor interaction pathway. They were predicted to interact with two transcription factors (FOXL1 and YY1) and several chemicals. Conclusions: This study identifies BDH1 and PIK3C2G as candidate genes associated with CM and ES-related pathways in RSA.