Work

The conserved molecular mechanism of erectile dysfunction in type 2 diabetes rats and mice by cross-species transcriptomic comparisons

Year: 2025

Type: article

Abstract: Background The poor clinical situation of type 2 diabetes-induced erectile dysfunction (T2DMED) creates an urgent need for new therapeutic targets. Aim To reveal the conserved molecular mechanism of T2DMED across species. Methods T2DMED rat and mouse models were constructed to extract mRNA from corpus cavernosum for high-throughput sequencing. The differentially expressed genes (DEGs) were analyzed and the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Protein–Protein Interaction Networks were performed by bioinformatics methods. Immunohistochemistry, immunofluorescence, hematoxylin- eosin and Masson staining were used for subsequent verification. Outcomes Cross-species transcriptomics of T2DMED rats and mice were analyzed and validated. Results Gene expression patterns in normal corpus cavernosum of mice and rats showed a strong correlation (r = 0.75, P < 2.2 × 10-16), with a total of 15 691 homologous genes identified. In both species, 553 homologous down-regulated DEGs were identified, mainly enriched in pathways related to smooth muscle and mitochondrial functions, as revealed by KEGG and GO analyses. Immunohistochemistry and immunofluorescence confirmed the decreased expression of α-smooth muscle actin and Uqcr10 in cavernosum tissues of T2DMED mice and rats. Additionally, 239 homologous up-regulated DEGs were identified, which were enriched in the Wnt signaling pathway and extracellular matrix composition. Subsequent experiments confirmed increased β-catenin expression and significant collagen accumulation, indicating fibrosis in T2DMED. Clinical implications To provide a new direction for improving the erectile ability of patients with T2DMED. Strengths and limitations The main strength is that cross-species transcriptomic sequencing has revealed the conserved molecular mechanisms of T2DMED. The main limitation is the lack of further validation in the T2DMED patients. Conclusions Cross-species transcriptomic comparisons may offer a novel strategy for uncovering the underlying mechanisms and identifying therapeutic targets for T2DMED.

Source: Sexual Medicine

DOI: 10.1093/sexmed/qfaf007

Authors: Ming Xiao, Huanqing Zeng, Yanghua Xu, Jiarong Xu, Xiaoli Tan, Yuxin Tang

Institution: Fifth Affiliated Hospital of Sun Yat-sen University

Language: English

Topic: Sexual function and dysfunction studies

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,750