Sexual Medicine最新文献

Introduction: Abnormal spontaneous neural activity has been detected in the brain of anejaculation patients. It has been confirmed that anejaculation may be associated with altered regional activation in the brain.

Aim: This study aimed to explore the changes of grey matter in the brain of anejaculation patients.

Methods: Structural magnetic resonance imaging data were collected from 20 primary intravaginal anejaculation (PIAJ) patients and 16 matched healthy controls (HCs). The 3D high resolution T1 weighted images were processed to calculate the grey matter volume and density by the method of voxel-based morphometry analysis.

Outcomes: Differences of grey matter volume and density were compared between groups, and receiver operating characteristic curve was performed to evaluate the values of altered brain regions in distinguishing PIAJ from HCs.

Results: PIAJ patients showed increased grey matter volume in the right supplementary motor area, right inferior temporal gyrus, right superior and inferior occipital gyrus, part of the left precuneus and decreased grey matter grey matter in another part of the left precuneus. In addition, increased grey matter density of the right supplementary motor area, right postcentral gyrus, right inferior temporal gyrus, left middle frontal gyrus, left inferior temporal gyrus and decreased grey matter density of the left precuneus were revealed in PIAJ patients. Both abnormal grey matter volume and altered grey matter density exhibited satisfactory performance in distinguishing PIAJ from HCs.

Clinical implications: These findings suggested that increased microstructural changes of grey matter might be associated with the increased inhibiting effect of the brain on ejaculation.

Strengths & limitations: This study provided new insights into the pathological mechanism underlying PIAJ, These findings are exploratory and that future longitudinal or comparative studies (eg, PIAJ vs. premature ejaculation) will be necessary to clarify whether these changes are predisposing, consequential, or potentially modifiable.

Conclusion: These findings indicated that patients suffering from PIAJ might exhibit abnormal grey matter volume and density in some brain regions, which might be linked to the inability to ejaculate intravaginally. PIAJ patient showed more increased indicators of grey matter when compared with premature ejaculation patients, which often had decreased brain function.

Background: The urgent need for new treatments is driven by the challenging clinical situation of age-related erectile dysfunction (ARED).

Aim: To clarify the conserved molecular mechanisms of ARED across species using multi-omics.

Methods: Rat and mouse models with ARED were developed to facilitate the extraction of mRNA and proteins from the corpus cavernosum for high-throughput sequencing. Bioinformatics techniques were employed to analyze differentially expressed genes and to conduct analyses using the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and protein-protein interaction networks. Verification of the results was carried out using immunofluorescence, hematoxylin-eosin staining, and Masson staining.

Outcomes: The multi-omics profiles of ARED rats and mice were analyzed and validated across species.

Results: In both species, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses of transcriptomic and proteomic data revealed that differentially expressed genes were predominantly enriched in pathways associated with alterations in extracellular matrix composition, downregulation of mitochondrial activity, and disruption of protein homeostasis. Immunofluorescence analysis demonstrated an upregulation of reactive oxygen species expression, coupled with a downregulation of Aldh18a1, collagen, and collagen I expression in the corpus cavernosum of mice and rats with ARED.

Clinical implications: To offer a novel approach for enhancing the erectile function in patients with ARED.

Strengths and limitations: The primary strength of this study lies in its utilization of cross-species multi-omics sequencing, which has elucidated the conserved molecular mechanisms underlying ARED. However, a significant limitation is the absence of subsequent validation in patients with ARED.

Conclusions: Cross-species multi-omics comparisons present a potentially innovative approach for elucidating the underlying mechanisms and identifying preventive and therapeutic targets for ARED.

Background: Hyperglycemia induces the development of cavernosa atherosclerosis and fibrosis, and transforming growth factor-β1 (TGF-β1) plays an important role in the induction, promoting fibrosis in corporal tissue, which replaces the normal corpora cavernosa with fibrotic tissue.

Aim: This study explored the role of Angiotensin (1-7) (Ang 1-7) and the regulatory mechanism underlying fibrosis in the corpora cavernosa.

Methods: Primary rat corpus cavernosum smooth muscle cells (CCSMCs) were cultured under normal and high glucose (HG) with or without Ang 1-7. The protein levels of TGF-β1, Collagen I, TGF-β receptor-I (TβRI), and caveolin-1 (Cav-1) were evaluated by western blotting. Reactive oxygen species (ROS) and peroxynitrite (ONOO^-) levels in cell culture supernatants were measured by enzyme-linked immunosorbent assay. Intracellular calcium content was determined by flow cytometry.

Outcomes: High glucose significantly increased the protein levels of TGF-β1 and Collagen I, triggered oxidative stress, modulated the AKT signaling pathway, and elevated intracellular calcium ion levels in CCSMCs. Angiotensin (1-7) treatment significantly attenuated HG-induced adverse effects in CCSMCs.

Results: The protective effects of Ang 1-7 against fibrosis in HG-exposed CCSMCs were associated with the downregulation of TGF-β1 levels, accompanied by the attenuation of oxidative stress. The Ang1-7-induced effects in CCSMC cells are mediated through the inhibition of the TGF-β1/AKT signaling pathway.

Clinical translation: Our studies provide new insights into the critical role of the TGF-β1/AKT signaling pathway in CCSMCs, identifying it as a potential therapeutic target for treating patients with erectile dysfunction.

Strengths and limitations: Angiotensin (1-7) is a unique peptide of the renin-angiotensin system with substantial therapeutic potential. This study assessed the therapeutic effect of Ang 1-7 on the fibrotic process and provided new insights for clinical applications. The clinical formulation, drug stability, and in vivo bioactivity of Ang-1-7 remain to be fully investigated.

Conclusion: Angiotensin (1-7) exerts a protective effect on CCSMCs under HG conditions by modulating the TGF-β1/AKT signaling pathway.

[This corrects the article DOI: 10.1093/sexmed/qfaf037.].

Background: Peyronie's disease (PD) is a relatively common clinical disorder of the penis that causes curvature and erectile dysfunction. However, the pathophysiological processes of PD are not well understood in current animal models and there exists limited clinical treatment options, which significantly impedes translational research.

Aim: This study aimed to develop a novel rat model of PD induced by local surgical tunica albuginea trauma and compare it with the TGF-β-induced model to elucidate the scientific soundness and feasibility of the local surgical tunica albuginea trauma-induced PD model.

Methods: A total of 24 male standard deviation rats were randomly allocated into three groups: sham group, surgical trauma group, and TGF-β group. The sham group received a skin incision only, whereas the surgical trauma group and the TGF-β group underwent PD model establishment via microsurgical tunica albuginea trauma and TGF-β injection, respectively. Six weeks post-modeling, penile blood perfusion, degree of curvature and erectile function were quantified. Penile tissues were subsequently harvested for histological analysis and Western blotting was used to evaluate tunica albuginea fibrosis.

Outcomes: PD model of surgical tunica albuginea trauma was successfully established and exhibited more pronounced fibrotic phenotypes in the penile tunica albuginea.

Results: Compared with TGF-β-induced models, laser speckle imaging revealed significantly reduced penile blood perfusion in surgical trauma group, accompanied by more severe penile curvature with corresponding angular and curvature alterations. HE and Masson's trichrome staining demonstrated marked local thickening and significantly increased collagen deposition in the penile tunica albuginea of rats in the surgical trauma group. Sirius red staining revealed a marked increase in collagen I and collagen III content. Immunofluorescence staining and Western blot analysis revealed that the surgical trauma group exhibited more pronounced alterations in the expression levels of fibrosis-related markers (Fibronectin, α-SMA, Collagen I, and Collagen III) in penile tissue.

Clinical implications: The rat model of tunica albuginea surgical trauma provides a promising option for preclinical PD research.

Strengths and limitations: The tunica albuginea surgical trauma-induced PD model established in our study has been scientifically validated. However, the precise pathogenesis of the model requires further investigation.

Conclusion: The tunica albuginea surgical trauma-induced PD model was successfully established and demonstrates a more pronounced fibrotic phenotype in the penile tunica albuginea, potentially better recapitulating the pathophysiological processes of PD.

Background: While the relationship between gut microbiota and erectile dysfunction (ED) has been reported, the specific pathways involved remain unclear.

Aim: This study aims to investigate the causal relationship between gut microbiota and ED, and to identify the potential role of plasma metabolites as mediators.

Methods: Utilizing aggregated genome-wide association study (GWAS) data, a comprehensive two-sample Mendelian randomization (MR) analysis was performed involving 196 gut microbiota taxa, 1400 plasma metabolites and ED. Causal relationships between gut microbiota, plasma metabolites and ED were explored. In addition, mediation analysis was applied to identify the pathway from gut microbiota to ED mediated by plasma metabolites.

Outcomes: This study reveals that plasma metabolites act as mediators regulating the influence of gut microbiota on ED.

Results: MR analysis identified causal relationships between six gut microbial taxa and ED, with Butyrivibrio increasing the risk of ED, while Alistipes, Prevotella 9, Dialister, Marvinbryantia, and LachnospiraceaeUCG010 exhibited protective effects. Additionally, 45 plasma metabolites demonstrated causal associations with ED. Finally, mediation analysis revealed four mediation relationships. Sensitivity analysis indicated no heterogeneity or pleiotropy in this study.

Clinical implications: Modulating gut microbiota or targeting specific metabolites may offer new therapeutic approaches for ED, highlighting the potential for microbiome-based interventions.

Strengths and limitations: The MR approach and large-scale GWAS data provide robust causal evidence, but the findings are limited by their focus on European populations and lack of experimental validation. Further studies are needed to confirm these mechanisms in diverse cohorts and functional models.

Conclusion: This study establishes a causal link between gut microbiota, plasma metabolites, and ED, identifying specific microbial taxa and metabolites as key contributors to ED risk. The mediating role of plasma metabolites highlights potential therapeutic strategies, such as probiotics or dietary interventions targeting harmful metabolites.