Placental transcriptome profiling and immune signature differences in pregnancies with and without gestational diabetes mellitus: An observational study

Gestational diabetes mellitus (GDM) is associated with placental dysfunction, which contributes to adverse pregnancy outcomes. This study aimed to compare transcriptomic profiles and immune signatures in placentas from pregnancies with and without GDM. Placental tissues from 22 participants (12 GDM and 10 controls) were analyzed using ribonucleic acid sequencing. Differentially expressed genes were identified and subjected to gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. X-cell analysis was used to assess immune cell composition. Western blotting validated the expression of selected genes. A total of 1045 differentially expressed genes were identified. Among these, COL22A1, COL8A2, ACTC1, PAX6, PPP2R2C, G6PC were significantly upregulated. In contrast, LEP and ERBB2 were downregulated in GDM placentas. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that extracellular matrix organization, muscle contraction, and calcium signaling pathways were upregulated. Pathways involved in glucose import, amino acid transport, and the endoplasmic reticulum (ER) stress response were downregulated. X-cell analysis suggested alterations in stromal and immune cell composition, with increased myocytes and fibroblasts and reduced M2 macrophages in GDM placentas. We found that various molecular signatures, including composition, metabolism, ER stress, and immune cells, were altered in GDM placentas compared to controls. This study demonstrates that the GDM placentas exhibit significant transcriptomic alterations, including changes in metabolic, ER stress-related, and immune pathways. These findings highlight the role of placental remodeling in the pathophysiology of GDM and may provide insights for future research and potential therapeutic strategies.