Work

Identification of hypoxia- and mitochondria-related genes associated with recurrent spontaneous abortion: an integrative bioinformatics analysis and preliminary validation

Year: 2025

Type: article

Abstract: Background: Hypoxia and mitochondrial dysfunction have been implicated in recurrent spontaneous abortion (RSA), although the precise molecular mechanisms remain unclear. This study aimed to explore hypoxia- and mitochondria-related genes (HRGs and MRGs) that may be associated with RSA using integrative bioinformatics approaches and preliminary experimental validation. Methods: We analyzed transcriptomic data and curated a list of HRGs/MRGs, and subsequently identified differentially expressed genes (DEGs) between the RSA and control groups. Overlapping DEGs with HRGs and MRGs revealed candidate genes, which were further validated through machine learning and expression analysis. A nomogram was developed to predict RSA risk based on these genes. Additionally, functional enrichment analysis, immune infiltration profiling, and regulatory network analysis were performed, followed by drug prediction. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) confirmed the differential expression of genes. Results: BSG and TRAK1 were identified, via bioinformatics and RT-qPCR validation, as hypoxia- and mitochondria-related genes associated with RSA. Gene Set Enrichment Analysis (GSEA) suggested that BSG and TRAK1 may be associated with biological pathways such as zinc ion homeostasis and NK cell-mediated cytotoxicity, although their mechanistic roles remain unclear. The nomogram exhibited strong predictive accuracy. BSG and TRAK1 were positively correlated with resting memory CD4+ T cells, with their expression regulated by transcription factors EHMT2 and SUPT5H. Drug prediction analyses, based on gene expression patterns, suggested captopril, valproic acid, and compound 7646-79-9 as potential candidates for future experimental investigation, although their mechanistic roles remain to be validated. Conclusion: BSG and TRAK1 are upregulated in RSA and associated with RSA-relevant biological processes. While their functional roles require further investigation, these genes represent promising candidates for future mechanistic and clinical studies.

Source: PeerJ

DOI: 10.7717/peerj.20467

Authors: Lin Chen, Caini Wei, Lili Gao, Dongyang Lu

Institutions: Guangxi Medical University, First Affiliated Hospital of GuangXi Medical University

Language: English

Topic: Reproductive System and Pregnancy

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,395