Expression of homeobox B13 gene and metabolomics study in placental tissues of gestational diabetes mellitus

Our study aimed to investigate the expression characteristics of the homeobox B13 (HOXB13) gene in placental tissues of gestational diabetes mellitus (GDM) and its impact on placental metabolic function. Placental tissues from 30 GDM patients and normal pregnancy cases were collected. The expression of HOX family genes (including HOXB13 and HOXA2 among seven genes) was screened using quantitative polymerase chain reaction, and the protein expression of HOXB13 was validated by Western blot and immunohistochemistry. Untargeted metabolomics analysis using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was performed to examine metabolic differences in placental tissues, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment was applied to interpret metabolic regulation networks. The results showed that the mRNA and protein expression of HOXB13 were significantly lower in the GDM placentas compared to the normal pregnancy group. A total of 337 differential metabolites were identified, with the highest proportion being lipids and lipid-like molecules (37.96%). The levels of glucose and galactose in the GDM group were significantly reduced. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that these differential metabolites were enriched in pathways related to steroid hormone biosynthesis, retinol metabolism, and arachidonic acid metabolism. We conclude that HOXB13 is downregulated in GDM placentas, and its expression is closely associated with dysregulated glucose-lipid metabolism and abnormalities in key metabolic pathways. HOXB13 may serve as a potential biomarker and therapeutic target for GDM