Integrative analysis of transcriptomics and metabolomics reveals mitochondria function genes and associated metabolite pathways in endometritis.

Abstract

Endometritis is an inflammatory endometrium condition affecting reproductive outcomes. However, the pathology of endometritis is poorly understood. Thus, we attempted to investigate the pathogenic mechanism of endometritis and discover potential biomarkers. Transcriptome sequencing was performed on endometritis patient-derived endometrial tissues (n = 3) and normal controls (n = 5). Differentially expressed genes (DEGs) between disease and control groups were identified. Mitochondrial genes were filtered based on MitoCarta3.0. Small RNA sequencing (9 disease samples vs. 6 controls) was combined with differentially expressed (DE) mitochondrial genes to generate a competing endogenous RNA (ceRNA) network, followed by protein-protein interaction network analysis. Metabolome analysis was conducted to explore differentially expressed metabolites (4 cases vs. 4 controls). Comparative analysis revealed a total of 1,507 DEGs in disease group relative to controls, which were implicated in 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. ALDH3A2, ACSS3, and KMO showed interactions with metabolites and significant pathways. Hub genes (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.