Background: Brain-derived neurotrophic factor (BDNF), as a member of the nerve growth factor family, has been mentioned more and more frequently in recent literature reports. Among them, content about the male genitourinary system is also increasing. Objective and Rationale: BDNF plays an important role in the male genitourinary system. At the same time, the literature in this field is constantly increasing. Therefore, we systematically summarized the literature in order to more intuitively show the function of BDNF and its receptor in the male genitourinary system and its potential clinical application. Search Methods: An electronic search of, e.g., PubMed, scholar.google and Scopus, for articles relating to BDNF and its receptor in the male genitourinary system. Outcomes: In the male genitourinary system, BDNF and its receptors TrkB and p75 participate in a series of normal physiological activities, such as the maturation and morphogenesis of testes and epididymis and maintenance of isolated sperm motility. Similarly, an imbalance of the circulating concentration of BDNF also mediates the pathophysiological process of many diseases, such as prostate cancer, benign prostatic hyperplasia, male infertility, diabetes erectile dysfunction, penile sclerosis, and bladder fibrosis. As a consequence, we conclude that BDNF and its receptor are key regulatory proteins in the male genitourinary system, which can be used as potential therapeutic targets and markers for disease diagnosis.

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.