Identification of Potential Biomarkers and Pathways for Asthenozoospermia by Bioinformatics Analysis and Experiments

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2024 Jun 12

PMID 38863929

Authors

Hui Lu

Liqiang Zhao

Anguo Wang

Hailing Ruan

Xiaoyan Chen

Yejuan Li

Jiajia Hu

Weiying Lu

Meifang Xiao

Affiliations

Soon will be listed here.

Abstract

Background: Asthenozoospermia, a type of male infertility, is primarily caused by dysfunctional sperm mitochondria. Despite previous bioinformatics analysis identifying potential key lncRNAs, miRNAs, hub genes, and pathways associated with asthenospermia, there is still a need to explore additional molecular mechanisms and potential biomarkers for this condition.

Methods: We integrated data from Gene Expression Omnibus (GEO) (GSE22331, GSE34514, and GSE160749) and performed bioinformatics analysis to identify differentially expressed genes (DEGs) between normozoospermia and asthenozoospermia. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to gain insights into biological processes and signaling pathways. Weighted Gene Co-expression Network Analysis (WGCNA) identified gene modules associated with asthenozoospermia. Expression levels of key genes were assessed using datasets and experimental data. Gene Set Enrichment Analysis (GSEA) and correlation analysis identified pathways associated with the hub gene and explore the relationship between the and and mitochondrial autophagy-related genes. Competitive endogenous RNA (ceRNA) networks were constructed, and experiments using exosome samples were conducted to validate this finding.

Results: was identified as a marker gene in asthenozoospermia, involved in autophagy, ATP-dependent chromatin remodeling, endocytosis, and cell cycle, etc. The ceRNA regulatory network (LINC00893/miR-125a-5p/COQ9) was constructed, and PCR demonstrated that and were downregulated in asthenozoospermia, while miR-125a-5p and m6A methylation level of were upregulated in asthenozoospermia compared to normozoospermic individuals.

Conclusion: The ceRNA regulatory network (/miR-125a-5p/) likely plays a crucial role in the mechanism of asthenozoospermia. However, further functional experiments are needed to fully understand its significance.

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