Andrology最新文献

Background: Triptolide is a traditional Chinese medicine used to treat autoimmune and inflammatory diseases. However, one adverse side effect of triptolide is male infertility. While triptolide's testicular toxicity is well-documented, its impact on epididymal function, particularly its role in triggering immune dysregulation (e.g., epididymitis secondary to germ cell damage), remains unclear.

Objectives: The objective is to explore the damage to male germ cells in mice after triptolide administration and analyze how the male germ cells' damage leads to epididymitis.

Materials and methods: Triptolide was orally administered to male C57BL/6J mice via gavage, inducing male germ cell damage that subsequently triggered epididymitis. Epididymal epithelial cells (EECs) were challenged with damaged male germ cells (DMGCs) and germ cell components to trigger an immune response.

Results: Oral administration of triptolide in mice caused damage to male germ cells. These DMGCs accumulated in the epididymis and triggered epididymitis. The DMGC-triggered epididymitis was characterized by massive immune cell infiltration, primarily macrophages, lymphocytes, along with the upregulation of major inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and CXC chemokine ligand10 (CXCL10). Mechanistically, DMGCs and germ cell components, heat shock protein 60 (HSP60) and protamine, activated innate immune responses and induced inflammatory cytokine expression in EECs, which may contribute to epididymitis after triptolide administration.

Discussion and conclusion: Triptolide may induce male germ cell damage, and DMGCs and germ cell components lead to non-infectious epididymitis. The findings provided novel insights into the mechanisms behind triptolide-induced male infertility and can aid in developing preventive and therapeutic strategies to address this side effect.

Background: Reconstructing the urethra presents in hypospadias surgery is difficult. Occasionally, the urethral plate (UP) may be quite narrow, necessitating augmentation or replacement to achieve additional tubularization.

Objective: The objective of this research was to assess the application of modified dorsal inlay graft (mDIG) and tubularized incised plate (TIP) urethroplasties in patients with hypospadias and narrow UPs and to determine which method yields superior functional and surgical outcomes.

Materials and methods: The medical records of 114 patients with distal/midshaft hypospadias and narrow UPs who were treated at our hospital from December 2020 to June 2024 were analyzed in this retrospective cohort study. These individuals were categorized into two distinct groups: the TIP and the mDIG groups. Standard preoperative characteristics, surgical technique, postoperative complication rate, maximum urinary flow rate (Q_max), and the hypospadias objective scoring evaluation (HOSE) score were analyzed to assess treatment efficacy in both groups.

Results: No significant differences in patient age, meatus location, UP width, coronal diameter, or urethral length were observed between the two groups. Sixty-five patients (57.0%) underwent TIP urethroplasty, and 49 patients (43.0%) underwent mDIG urethroplasty. A statistically significant difference in operative time was observed, with operative times of 108 (101-118.5) and 85 (78-92.5) min (p < 0.001) in the mDIG and TIP groups, respectively. The mDIG group demonstrated a better HOSE score than the TIP group, with 5 (10.2%) versus 18 (27.7%) patients scoring less than 16 points and 44 (89.8%) patients versus 47 (72.3%) scoring 16 points, respectively. Three months after surgery, the Q_max was 11.7 ± 3.4 mL/s in the mDIG group versus 9.43 ± 3.1 mL/s in the TIP group (p < 0.05).

Discussion and conclusion: mDIG urethroplasty has a high success rate, ensuring both optimal aesthetic and functional outcomes in the short term, which, justifies the additional operative time.

Background: Many andrologists put more attention on the predictive factors of successful sperm extraction in testicular sperm aspiration (TESA) or microdissection testicular sperm extraction (micro-TESE), while the importance of laboratory processing of testicular tissue has been neglected. In fact, for non-obstructive azoospermia (NOA) patients, laboratory procedure of testicular tissue is as important as the surgery itself to find testicular sperm, yet there is no standard procedure for laboratory management of testicular tissue.

Objectives: To establish a laboratory processing for testicular tissue, and to further evaluate the effectiveness of enzymatic digestion and staining for NOA patients with no spermatozoa found after mechanical mincing.

Materials and methods: We enrolled 811 patients who underwent TESA or micro-TESE from July 2023 to December 2024, among whom 466 were diagnosed with obstructive azoospermia and 345 were diagnosed with NOA. The main outcome measure was the sperm retrieval rate (SRR) after enzymatic digestion and the sperm detection rate (SDR) after staining.

Results: In this study, testicular spermatozoa was found after mincing in 466 TESA patients (466/583, 79.9%) and 74 micro-TESE patients (74/228, 32.5%). Of the 237 patients for whom spermatozoa were not identified after mincing, spermatozoa were detected in 55 (23.21%) patients after enzyme digestion and staining. The additional SRR contributed by enzymatic digestion alone was 13.1%, while staining contributed an additional SDR of 10.1%. Using multivariable logistic regression analysis, the seminiferous tubule diameter was the only predictor of identifying spermatozoa in NOA patients after enzymatic digestion and staining.

Discussion and conclusion: In conclusion, we establish a three-step laboratory processing method for testicular tissue. This study provides strong evidence that enzymatic digestion improves SRR in NOA patients, while staining contributes additional detection value (SDR) when mechanical processing fails, the combined additional value of enzymatic digestion and staining is 23.2%, although only enzymatic digestion contributes to SRR. What is more, the current study showed that seminiferous tubule diameter is a powerful predictor for sperm retrieval, offering real-time, actionable intraoperative guidance. However, the single-center design and lack of live birth outcome data limit the external validity and generalizability of this study.

Background: Male fertility can be influenced by environmental factors, including seasonal variation, which may cause fluctuations in semen quality. However, studies to date have reported inconsistent findings, limiting our understanding of how seasonality affects reproductive potential. A clearer picture of these patterns is essential for optimizing the timing and interpretation of fertility evaluations.

Objective: To systematically review and meta-analyze existing data on seasonal differences in semen analysis parameters.

Materials and methods: We searched PubMed, Web of Science, and Scopus up to March 18, 2025 using the key search terms of "semen parameter" and "seasonality," along with their related terms. Initial search yielded 641 studies. The inclusion criteria were original articles or conference abstracts that investigated any human semen parameters across different seasons. After screening, 21 studies were included for meta-analysis. We calculated the pooled weighted mean differences in semen parameters across different seasons using the random-effects models.

Results: Meta-analyses of 21 studies with high methodological quality showed that winter and spring had better semen quality than summer and fall, in that they had higher sperm concentration of 3.24-6.07 million/mL, higher total sperm count of 14.63-19.74 million, and lower slow motility of 5.17%-11.75%. Additionally, winter had greater normal morphology of 1.30% than both fall and summer. Spring also had greater total motile sperm count of 4.34-4.38 million compared with fall and summer and greater normal morphology of 0.88% than summer. Summer had lower slow motility of 5.05% than fall.

Conclusion: This meta-analysis showed seasonal variations in semen parameters, with generally better semen quality in winter and spring compared with summer and fall. Specifically, these seasons were associated with higher sperm concentration, greater total sperm count, and reduced slow motility compared with summer and fall.

Background: Testicular torsion is a common urological emergency that can lead to irreversible spermatogenic dysfunction and infertility. Sophocarpine, derived from Sophora flavescens Ait, has demonstrated broad therapeutic effects, including protection against ischemia-reperfusion injury (IRI). However, its effects on testicular IRI remain underexplored.

Objective: This study aimed to assess the protective effects of sophocarpine on bilateral testes in a rat model and to investigate the underlying mechanisms involved.

Materials and methods: Male Sprague-Dawley rats were randomly assigned to five groups: the sham, control, sophocarpine, control + wortmannin, and sophocarpine + wortmannin groups (n = 7 rats per group). All groups, except for the sham group, underwent unilateral testicular IRI. The procedure involved 3 h of right spermatic cord torsion (720° clockwise) followed by 3 h of detorsion. Sophocarpine (administered at a dose of 30 mg/kg) was given to the rats in the respective treatment groups. The therapeutic effects were evaluated via histological analysis, oxidative stress assessment, inflammatory response measurement, protein analysis, and immunohistochemistry.

Results: Sophocarpine treatment significantly protected the bilateral testes after unilateral testicular torsion-detorsion, as indicated by a reduction in the testis weight-to-body weight (TW/BW) ratio, testicular volume, and structural damage. Additionally, sophocarpine increased the seminiferous tubule diameter and epithelial height. The treatment also suppressed oxidative stress and inflammatory responses. Notably, sophocarpine inhibited ferroptosis through the AKT signaling pathway, as evidenced by increased phosphorylation of AKT in the testes. Furthermore, the AKT inhibitor wortmannin reversed both the phosphorylation of AKT and the protective effects of sophocarpine on the testes.

Discussion and conclusion: Sophocarpine effectively protects the bilateral testes after unilateral testicular torsion-detorsion, with protective effects through ferroptosis mediated by the AKT signaling pathway, highlighting its potential as a therapeutic target in testicular IRI.

Background: Asthenozoospermia is a significant contributing factor to male infertility. Accumulating evidence indicates that impaired sperm motility is closely linked to dysregulated microRNA expression during spermatogenesis. Seminal plasma exosomes are enriched with diverse microRNAs, which play pivotal roles in modulating sperm motility, the acrosome reaction, capacitation, and fertilization.

Objective: To investigate the association between exosomal microRNA profiles and sperm motility by comparing microRNA expression patterns in seminal plasma exosomes from asthenozoospermic patients and healthy controls, thereby elucidating the molecular mechanisms underlying exosomal microRNA-mediated regulation of sperm motility.

Materials and methods: Seminal plasma exosomes were isolated from 21 asthenozoospermic patients and 21 age-matched healthy donors via ultracentrifugation, followed by characterization via transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. Exosomal microRNA profiles were analyzed via unique molecular identifier-based small RNA sequencing to identify motility-associated microRNAs.

Results: Comparative analysis revealed 13 significantly upregulated microRNAs in the exosomes of asthenozoospermic patients, among which hsa-miR-7-5p exhibited the greatest abundance. Functional enrichment analysis revealed that the target genes of hsa-miR-7-5p were associated primarily with cellular metabolism, macromolecule metabolic processes, and nitrogen compound metabolism, as well as several crucial signaling pathways, including mTOR signaling, endocrine resistance, and gonadotropin-releasing hormone secretion. A dual-luciferase reporter assay verified that hsa-miR-7-5p directly targets rapidly accelerated fibrosarcoma 1, a pivotal component of the gonadotropin-releasing hormone signaling pathway.

Discussion and conclusion: hsa-miR-7-5p may regulate sperm motility through the rapidly accelerated fibrosarcoma 1 -mediated gonadotropin-releasing hormone secretion and MAPK signaling networks. Our findings highlight the potential role of exosomal microRNAs in male infertility. Future prospective studies are warranted to elucidate the molecular mechanisms underlying the regulation of sperm motility.

Background: Histone methylation plays a crucial role in regulating chromatin architecture and gene expression during spermatogenesis. H3K4me3 is enriched at the transcription start sites of active genes, whereas H3K27me3 is deposited on chromatin to confer transcriptional repression. However, the dynamics of H3K4me3 and H3K27me3 modifications in the differentiation of postnatal Leydig cells remain poorly characterized.

Objectives: The purpose of this study was to elucidate the dynamics of H3K4me3 and H3K27me3 modifications in the differentiation of postnatal Leydig cells.

Methods: Through an integrated analysis of single-cell RNA-seq (scRNA-seq), cleavage under targets and tagmentation sequencing (CUT&Tag-seq), bulk RNA-seq, and immunohistochemistry across different developmental stages of mouse Leydig cells, we mapped the stage-specific landscapes of H3K4me3 and H3K27me3.

Results: Our results demonstrate that during progenitor to immature Leydig cell differentiation, H3K4me3 levels exhibited a diphasic fluctuation pattern (first decreasing and then increasing), contrasting with the progressive accumulation of H3K27me3. In progenitor Leydig cells, the resolution of bivalent chromatin domains (accounting for 24.5% of promoters) helps balance cell proliferation and differentiation. Strikingly, steroidogenic genes such as Star, Cyp17a1, and Hsd17b3 are exclusively regulated by H3K4me3 and lack H3K27me3 marking. In terminally differentiated adult Leydig cells, H3K4me3 sustains the steroidogenic capacity by activating transcription factors (such as Gata6, Cebpb, Nr1d1) and maturation markers (including Hsd17b3, Insl3, Sult1e1), while H3K27me3 permanently silences proliferation-related networks (such as Ccna2, Mki67, Ccnd1) to eliminate the self-renewal potential of these cells.

Discussion and conclusion: Our work identifies an H3K4me3/H3K27me3-transcription factors (TFs)-target gene axis as a central regulatory mechanism governing postnatal Leydig cell differentiation. This discovery clarifies how this axis endows Leydig cells with steroidogenic potential while suppressing stemness properties.

Background: Ejaculatory dysfunction (EjD) is a prevalent sexual disorder. Because of the private nature of this condition, few patients are willing to discuss it openly or seek medical help, as this may cause them embarrassment. Internet searches are increasingly becoming the primary source of health information for individuals with sexual dysfunctions. However, given the wide variability in online resource quality, rigorous evaluation of both content reliability and textual accessibility becomes essential.

Methods: We systematically analyzed the top 100 Google search results for each of the following EjD-related terms: premature ejaculation (PE), delayed ejaculation (DE), retrograde ejaculation (RE), anejaculation, painful ejaculation, anorgasmia, and hematospermia. After applying pre-defined inclusion/exclusion criteria, two board-certified urologists independently evaluated eligible websites using standardized tools: the Journal of the American Medical Association (JAMA) benchmark criteria (for credibility), the DISCERN instrument (for health information quality), and validated readability metrics (Flesch Reading Ease [FRE], Gunning Fog index, and Simple Measure of Gobbledygook [SMOG] index).

Results: Our systematic evaluation of 345 websites revealed that commercial entities constituted the predominant source (n = 221, 64.1%) of online health information regarding ejaculatory dysfunction. Quality assessment using the DISCERN instrument demonstrated "fair" ratings for resources addressing PE, DE, RE, and anorgasmia, while those covering anejaculation, painful ejaculation, and hematospermia scored in the "poor" range. Analysis of ejaculatory disorder websites revealed mean JAMA benchmark scores of 2.0, with disclosure as the highest-scoring domain. Additionally, FRE scores for these websites indicate a reading difficulty level categorized as "difficult", which is comparable to college-level reading proficiency.

Discussion and conclusion: While online resources on EjD may serve as supplementary patient education materials, our analysis reveals significant limitations in their readability. These findings underscore the need for developing standardized quality control measures to systematically monitor and manage health information available online.

Background: Lichen sclerosus is a chronic, inflammatory, scarring disease of the skin that manifests mostly in the genital region.

Objective: We studied the histomorphological characteristics, grade, and pattern of inflammation in male pediatric patients with lichen sclerosus. We also compared the expression of selected miRNAs in lichen sclerosus tissue, adjacent non-lichen sclerosus tissue from the same patient, and healthy male pediatric patients.

Results and discussion: According to the type of inflammation/lymphocytic distribution, we categorized patients into four groups with the following features: (i) dominant lichenoid basal superficial inflammation, (ii) dominant band-like lymphocytic infiltration in the papillary sublayer of the dermis, (iii) mixed lymphocytic inflammation combining both patterns, and (iv) lymphocytic depletion with extensive fibrosis. The extent of inflammation was graded, with patients being categorized into weak, moderate, and strong inflammation groups. In terms of miRNA expression, hsa-miR-146a-5p, hsa-miR-146b-5p, hsa-miR-150-5p, and hsa-miR-155-5p were significantly upregulated, and hsa-miR-199b-5p and hsa-miR-200b-3p were significantly downregulated in lichen sclerosus tissue compared with adjacent normal tissue as well as normal tissue from male pediatric non-lichen sclerosus patients (p < 0.001). Hsa-miR-30b-5p was significantly downregulated in lichen sclerosus patients compared with male pediatric non-lichen sclerosus patients (p < 0.001). Pediatric male lichen sclerosus patients were categorized into two groups according to median age (≤9 years vs. >9 years); the early onset prepubertal patients presented, on average, a higher grade of inflammation (p = 0.020) and significantly higher miRNA hsa-miR-150-5p (p = 0.049) expression compared to the older group.

Conclusions: Histopathological investigations can distinguish lichen sclerosus patient groups with different extents of disease. miRNAs could serve as candidate diagnostic markers for lichen sclerosus in pediatric male patients and may represent future therapeutic targets.