Transcriptome Sequencing Identifies PCK1 and IRS4 as Key Regulators of Gestational Diabetes Mellitus in Placenta: A Pilot Study

Wenwen Wang,1,* Qianrui Zhang,2,* Jing Lu,2 Li Zhou1 1Department of Obstetrics and Gynecology, Capital Medical University Affiliated Beijing Tongren Hospital, Beijing, People’s Republic of China; 2Department of Endocrinology, Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Lu, Email [email protected] Li Zhou, Email [email protected]: To identify key molecular regulators of GDM in placental tissues using transcriptome sequencing.Methods: This study employed transcriptome sequencing to investigate placental tissue from GDM patients (n=7) and healthy controls (n=6), aiming to identify key molecular regulators and pathways underlying GDM pathogenesis.Results: We identified 505 differentially expressed genes (DEGs), including 216 upregulated and 289 downregulated genes. Notably, PCK1 (phosphoenolpyruvate carboxykinase 1) and IRS4 (insulin receptor substrate 4) emerged as critical regulators. Quantitative real time PCR validation confirmed significant downregulation of PCK1 and upregulation of IRS4 in GDM placentas. Functional enrichment analysis revealed that PCK1 is associated with the CLINK/HLA-G/INAVA/KLRC2/PCK1/RBP4/SLAMF6 pathway, which was suppressed in GDM, while IRS4 correlated with the dysregulated AGRP/IRS4/RXRG axis.Conclusion: These findings highlight the roles of placental PCK1 and IRS4 in GDM. Further mechanistic studies, including protein-level validation and animal models, are warranted to explore these pathways as potential diagnostic or therapeutic targets for GDM. Keywords: gestational diabetes mellitus, placenta, transcriptome sequencing, PCK1, IRS4