Integrative analysis of transcriptomics and metabolomics reveals candidate biomarkers and associated metabolite pathways in endometritis.

Purpose: Endometritis is an inflammatory endometrium condition affecting reproductive outcomes. However, the pathology of endometritis is poorly understood. Thus, we aimed to elucidate the mechanism and identify potential biomarkers for endometritis. Methods: Transcriptome sequencing was performed on endometrial tissues collected from patients with endometritis (n = 3) and normal controls (n = 5). Differentially expressed genes (DEGs) between disease and control groups were identified, followed by Gene Set Enrichment Analysis. Mitochondrial genes were filtered based on MitoCarta3.0. Small RNA sequencing (9 disease samples vs. 6 controls) was combined with DE mitochondrial genes to generate a competing endogenous RNA (ceRNA) network, followed by protein-protein interaction network analysis. Hub genes associated with endometritis were identified, and immune infiltration and drug-target interaction analyses were performed. Metabolome analysis was conducted to explore differentially expressed metabolites (4 cases vs. 4 controls). Pathway enrichment analysis for hub genes and differentially expressed metabolites was conducted, and the disease-metabolic network was investigated. Results: A total of 1,507 DEGs were identified between the disease and control groups, closely related to adaptive immune response, cell chemotaxis, and chemotaxis signaling pathways. In total, 28 mitochondrial genes were differentially expressed and mapped to the ceRNA network. ALDH3A2, ACSS3, CYP24A1, and KMO were identified as hub genes and were closely associated with the infiltration of CD8 T cells. CYP24A1 was found to be the target of four drugs, including calcitriol and deferasirox. Five metabolic pathways were significantly enriched, including the citrate cycle (TCA cycle) and taurine and hypotaurine metabolism. The top four pathways were mapped to the disease-metabolic network. ALDH3A2, ACSS3, and KMO showed interactions with metabolites and significant pathways. Conclusion: Hub genes such as ALDH3A2 and ACSS3 play critical roles in the pathogenesis of endometritis by interacting with different metabolites. Our study offers candidate biomarkers for diagnosing and treating endometritis.