Asian journal of andrology最新文献

Erectile dysfunction (ED) is a prevalent disorder in men and has a negative impact on quality of life. Recent studies have demonstrated that shear stress plays a critical role in modulating vascular endothelial function. Shear stress is categorized into physiological (e.g., laminar) and pathological (e.g., low shear or oscillatory) shear stress. This study reviewed current literatures on the relationship between share stress and ED, aiming to advance strategies for enhancing erectile function. Physiological shear stress increases the production of nitric oxide by activating endothelial nitric oxide synthase, thereby maintaining vascular homeostasis and erectile function. However, pathological shear stress exacerbates inflammation and oxidative stress, inducing endothelial dysfunction and ED. Shear stress also regulates gene expression, cell behavior, and signaling pathways in endothelial cells through multiple mechanisms, ultimately influencing erectile function. Studies indicate that exercise improves endothelial function and mitigates oxidative stress and inflammation by inducing shear stress, thereby offering novel therapeutic avenues for ED. Future research should focus on elucidating shear stress-mediating regulatory mechanisms, and developing diagnostic and therapeutic strategies to improve clinical outcomes in patients with ED.

Chronic methamphetamine (Meth) exposure has been recognized as a critical risk factor for male reproductive dysfunction, yet its mechanistic underpinnings remain elusive. This study elucidates the molecular pathways through which Meth compromises spermatogenesis in a murine model. Male mice subjected to 15 days of chronic Meth administration presented severe testicular atrophy, characterized by seminiferous epithelial disorganization and diminished sperm reserves in both the testes and epididymides. Quantitative assessments revealed marked reductions in sperm motility and increased tail abnormalities. Transcriptomic profiling revealed significant down-regulation of methyltransferase-like 21C (Mettl21c), an undifferentiated spermatogonial-enriched methyltransferase, within pathways governing germ cell differentiation. Immunofluorescence analysis revealed predominant Mettl21c colocalization with undifferentiated spermatogonial marker ubiquitin carboxyl-terminal hydrolase L1 (Uchl1), with minimal overlap in tyrosine-protein kinase Kit (Kit) positive differentiated populations. In vitro suppression of Mettl21c in C18-4 lines triggered proliferation arrest and increased apoptosis. These findings establish Mettl21c as a pivotal mediator of Meth-induced spermatogenic failure through spermatogonial maintenance pathways. Our work provides novel insights into the epigenetic regulation of drug-associated male infertility and identifies Mettl21c as a potential therapeutic target for preserving fertility in substance abuse cases.

Non-obstructive azoospermia (NOA) is characterized by the absence of spermatozoa in the ejaculate as a result of impaired spermatogenesis. MicroRNAs (miRNAs), a type of small non-coding RNAs, have emerged as promising biomarkers owing to their remarkable stability in biological fluids. This systematic review examines miRNA expression profiles reported in seminal plasma and testicular tissue from patients with NOA. From an initial set of 1061 records, 14 studies met stringent inclusion criteria. A total of 73 unique miRNAs were identified. Among these, six miRNAs were consistently downregulated, and only one miRNA, hsa-miR-31-5p, was consistently upregulated in the seminal plasma of NOA patients compared to fertile controls. Bioinformatic analysis revealed a regulatory network involving three downregulated miRNAs (hsa-miR-34c-5p, hsa-miR-34b-3p, and hsa-miR-202-3p) that converge on two key target genes: interleukin 6 receptor (IL6R) and secretion-associated ras-related GTPase 1A (SAR1A), which are implicated in inflammation and intracellular vesicle transport, respectively. Pathway enrichment analyses indicated that the target genes of dysregulated miRNAs were enriched in cancer-related pathways and processes involving nucleic acid metabolism. Given the reported increased cancer risk among azoospermic patients, these findings suggest that specific miRNAs in seminal plasma may serve as novel non-invasive biomarkers and point to shared molecular mechanisms potentially linking NOA and cancer etiology.

This multicenter study aimed to establish a quantitative, individualized surgical decision algorithm for pediatric hypospadias by analyzing multicenter penile anatomical data, surgical approaches, and follow-up outcomes. To achieve this purpose, clinical data from 1500 primary hypospadias cases across 17 tertiary centers in China (December 2018 to September 2021) were retrospectively reviewed, with patients stratified into urethral plate preservation group (n = 715) and transection group (n = 785). Using multivariate logistic regression, key predictors for intraoperative urethral plate transection were identified, and morphometric parameters were analyzed to guide surgical selection. This analysis led to the development of a predictive nomogram and risk stratification thresholds, which were subsequently validated. The results demonstrated that significant predictors of transection included glans length (odds ratio [OR]: 1.17, 95% confidence interval [CI]: 1.07-1.29), glans width (OR: 0.35, 95% CI: 0.29-0.43), and penile curvature (OR: 1.07, 95% CI: 1.06-1.08), with the nomogram showing excellent discrimination (area under the receiver operating characteristic curve [AUC]: 0.914 in training and 0.87 in validation). Furthermore, for urethral plate preservation, a urethral plate width threshold of 4.25 mm differentiated optimal candidates for tubularized incised plate urethroplasty (width ≥4.25 mm) versus onlay island flap (width <4.25 mm). Notably, in transected cases, a urethral defect length of >3.55 cm was associated with higher complication rates in single-stage repairs (45.8% vs 33.4%, P < 0.05), favoring staged approaches. This algorithm integrates preoperative morphometrics and intraoperative measurements to provide objective, quantifiable guidance for individualized surgical planning, particularly benefiting less experienced surgeons.

Sperm quality is crucial for sperm function and can even affect embryo quality and offspring health. Spermatid maturation is extremely complex, as spermatids undergo morphological changes, laying the foundation for the execution of sperm function. The function of sperm acrosome-associated 4 (SPACA4) in spermatogenesis is not well known. The present study revealed that SPACA4 was specifically expressed in the acrosomes and cytoplasm of mouse spermatids. Spaca4 knockout mice demonstrated that the loss of SPACA4 led to male subfertility. The quality of mature sperm was abnormal in Spaca4-/- mice, manifested by decreased motility and multiple deformities. Spaca4-/- sperm exhibited irregular nuclear shapes, abnormal nuclei with vacuoles, missing or incompletely fused acrosomes, and multiple cross-sections enclosed in the same sperm cell membrane. Electron microscopy and molecular expression analyses of testicles revealed that the loss of SPACA4 affected the differentiation of the acrosome, acroplaxome, and manchette, resulting in abnormalities in nuclear elongation, chromatin condensation, and flagellar development. Interestingly, SPACA4 did not regulate spermiogenesis via the acetylcholine signaling pathway. Analysis of the differential protein expression profile revealed that the expression of 9 proteins was significantly decreased in Spaca4-/- spermatids. A decreased protein, transformation-related protein 53 target 5 (TRP53TG5), was knocked down in spermatids and found that the phenotype was consistent with Spaca4 knockout mice. These results revealed that the absence of SPACA4 leads to abnormal spermatid maturation and affects sperm quality in mice. Abnormal sperm quality in Spaca4-/- mice results in decreased sperm capacitation and a decreased acrosome response, ultimately affecting the fertility of male mice.

Lead (Pb) exposure is a risk factor of male infertility, while the transcriptional and epigenetic changes associated with lead exposure in spermatozoa are poorly understood. Our previous findings revealed significant changes in DNA methylation of the calcium (Ca) homeostasis pathway of human spermatozoa in men with a blood Pb level over 5 µg dl-1, which was associated with decreased sperm motility. In this study, we explored the effects of Pb exposure on expression of differentially methylated genes (DMGs) by analyzing semen samples from six healthy, non-smoking, and non-drinking men (aged 20-40 years). Using methylated DNA immunoprecipitation sequencing (MeDIP-seq) and RNA sequencing (RNA-seq), we compared DNA methylation and RNA abundance patterns between two groups: three men with blood Pb level 0-2.5 µg dl-1 and three men with blood Pb level 5-10 µg dl-1. Additionally, we experimentally validated the regulatory function of the differentially methylated regions associated with 11 hub genes using dual-luciferase reporter assays. We revealed differences in promoter activity between methylated and unmethylated promoter regions of seven cloned genes, namely calcium voltage-gated channel subunit alpha1 H (CACNA1H), calcium voltage-gated channel subunit alpha1 G (CACNA1G), calcium voltage-gated channel subunit alpha1 I (CACNA1I), calcium/calmodulin dependent protein kinase II gamma (CAMK2G), ATPase sarcoplasmic/endoplasmic reticulum Ca²+ transporting 3 (ATP2A3), solute carrier family 8 member A2 (SLC8A2), and glutamate ionotropic receptor NMDA type subunit 2D (GRIN2D). Our results of Pb exposure-induced expression changes of essential genes associated with the calcium signaling pathway, particularly CACNA1H, SLC8A2, and GRIN2D, in spermatozoa, may be a potential cause of low sperm quality.

Male infertility poses a substantial healthcare challenge and severely impacts the lives of patients. We aimed to investigate the risk factors for infertility and abnormal semen parameters. We conducted a comprehensive search of the articles published in Web of Science, MEDLINE, and Embase databases from January 2000 to February 2025. Infertility, semen volume, sperm concentration, sperm count, sperm morphology, sperm motility, and sperm progressive motility were used as endpoints to evaluate the relevance of risk factors. A total of 43 studies were included, covering 67 risk factors associated with infertility and abnormal sperm parameters. A total of 249 effect sizes were scored individually using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool, of which 136 (54.6%) were classified as "very low", 59 (23.7%) as "low", and 54 (21.7%) as "moderate". Suffering from type 1 diabetes, metabolic syndrome, hyperthyroidism, systemic lupus erythematosus, chronic prostatitis, and leukocytospermia may increase the risk of abnormal semen parameters. Poor lifestyle habits (obesity, sleep disorders, and smoking), exposure to pollutants and various compounds (carbon disulfide, organophosphates, and lead), the use of medications (sulfasalazine, mesalazine, and selective serotonin reuptake inhibitors), and even some viral infections (severe acute respiratory syndrome coronavirus 2, human papillomavirus, and hepatitis viruses) were associated with decreased semen quality. Regular physical exercise, nut consumption, and adherence to a healthy dietary pattern may reverse this process. An increasing number of factors are associated with infertility; however, some of the aforementioned studies lack verification of causal relationships. Future studies need to be well designed to further confirm these relationships.

This study aimed to analyze the associations between urinary genistein, daidzein, and equol concentrations and semen parameters in Japanese men exposed to high levels of isoflavone in their diet. Between September 2020 and March 2021, men seeking fertility treatment (n = 157) at Sanno Hospital (Tokyo, Japan) and Tsukuba Gakuen Hospital (Ibaraki, Japan) provided spot urine and semen specimens on the same day. Sperm concentration, sperm count, and total sperm motility were quantified. Urinary isoflavones were measured using liquid chromatography-tandem mass spectrometry and adjusted for specific gravity. The median (interquartile range [IQR]) total sperm count and concentration were 112 × 106 (50 × 106, 221 × 106) and 39 × 106 (17 × 106, 72 × 106) ml-1, respectively. Men in the second, third, and fourth quartile of urinary daidzein concentration had -40% (95% confidence interval [CI]: -59%, -13%), -37% (95% CI: -56%, -9%), and -32% (95% CI: -53%, -3%) low sperm count, respectively, than those in the lowest quartile. Men in the second, third, and fourth quartile of urinary genistein concentration had -23% (95% CI: -47%, 12%), -50% (95% CI: -66%, -26%), and -29% (95% CI: -51%, 3%) low sperm count than those in the lowest quartile, respectively. Sperm count showed no association with urinary equol concentration (P > 0.05). No associations were observed between urinary isoflavones and total sperm motility. A higher isoflavone intake may be associated with reduced sperm concentration and count. The effect of these alterations in semen parameters on the fecundity of couples trying to conceive remains unknown.

Cryptorchidism is recognized as a significant risk factor for male germ cell tumors and infertility, with a complex and multifaceted mechanism contributing to male infertility. When the testes fail to descend into the scrotum, increased local temperature and pressure lead to increased apoptosis of spermatogenic and Sertoli cells. Additionally, disruptions in the hypothalamic-pituitary-gonadal axis result in decreased testosterone levels within the testes, and abnormal secretion of follicle-stimulating hormone and luteinizing hormone, negatively impacting spermatogenesis. Cryptorchidism also induces increased oxidative stress within the testes, leading to sperm DNA damage and impairment of the sperm plasma membrane, hindering sperm-oocyte fusion. Unilateral cryptorchidism may cause injury to the ipsilateral genitofemoral nerve, further affecting the contralateral testis by increasing oxidative stress and apoptosis. Moreover, the production of antisperm antibodies can trigger autoimmune responses, potentially damaging germ cells and contributing to infertility. Damage to type A dark spermatogonia (type Ad spermatogonia) is also considered a high-risk factor for male infertility. Understanding the mechanisms by which cryptorchidism leads to male infertility may provide new avenues for enhancing fertility in affected patients.

To evaluate the prognostic significance of prostate-specific antigen (PSA) decline depth and duration in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC) undergoing abiraterone treatment. We retrospectively analyzed data from 153 high-risk patients with mHSPC receiving first-line abiraterone therapy. Patients were stratified based on PSA dynamics during treatment. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to assess the associations between PSA decline patterns, PSA progression-free survival (PSA-PFS), radiographic PFS (rPFS), and overall survival (OS). Among the 153 patients, 85 exhibited PSA nadir <0.2 ng ml-1, 48 had PSA nadir level ranging from 0.2 ng ml-1 to 4 ng ml-1, and 20 presented with a PSA nadir >4 ng ml-1. During abiraterone treatment, PSA nadir <0.2 ng ml-1 was significantly associated with improved median PSA-PFS (51.0 months vs 18.5 months vs 6.9 months, P < 0.0001), median rPFS (52.0 months vs 24.3 months vs 10.3 months, P < 0.0001), and median OS (not reached vs 48.5 months vs 28.1 months, P < 0.0001) compared with PSA nadir ≥0.2 ng ml-1 and <4 ng ml-1, and PSA nadir ≥4 ng ml-1. In the cohort with PSA nadir <0.2 ng ml-1, achieving PSA <0.2 ng ml-1 within 6 months and maintaining this level for over 10 months significantly enhanced clinical outcomes, as evidenced by median PSA-PFS (not reached vs 26.9 months, P < 0.0001), median rPFS (not reached vs 27.5 months, P < 0.0001), and median OS (not reached vs 44.4 months, P < 0.0001). Cox regression analysis revealed that achieving PSA <0.2 ng ml-1 within 6 months post-treatment and sustaining this level for over 10 months are independent prognostic factors. In high-risk patients with mHSPC receiving first-line abiraterone, sustained PSA suppression is a key indicator of therapeutic response. The rate, depth, and duration of PSA decline are critical prognostic factors.