Mitochondrial dysfunction and immune microenvironment in gestational diabetes mellitus: insights from bioinformatics analysis and experimental validation - PubMed
5 hours ago
- #mitochondrial dysfunction
- #immune microenvironment
- #gestational diabetes
- Gestational diabetes mellitus (GDM) is linked to mitochondrial dysfunction and immune microenvironment changes.
- Transcriptomic data from GEO and mitochondrial gene lists from MitoCarta3.0 were used to identify differentially expressed mitochondrial-related genes (Mito-RGs) in GDM.
- Machine learning algorithms (LASSO, RF, XGBoost) identified hub Mito-RGs: DHRS2, STX17, and TIMM44.
- A predictive nomogram for GDM was developed based on Mito-RGs scores, showing strong predictive performance.
- Single-cell RNA sequencing revealed higher proportions of epithelial cells, macrophages, and NK cells in GDM placental tissues, with reduced tissue stem cells.
- Glycolysis and hypoxia-related pathways were enriched in epithelial and stem cells, while inflammatory pathways were enriched in macrophages.
- Immunohistochemistry confirmed elevated DHRS2 protein levels in GDM patient placentas and mouse models.
- Mitochondrial dysfunction contributes to pro-inflammatory reprogramming of the placental immune microenvironment in GDM, suggesting potential therapeutic targets.