Andrology最新文献

Background: Obstructive azoospermia, with a sustained elevation in intratesticular pressure, leads to seminiferous epithelium degeneration. However, studies using efferent duct ligation have not fully elucidated the chronic changes in the testis caused by obstruction.

Objective: Using the efferent duct transection model, we aimed to elucidate the temporal and spatial progression of spermatogenic impairment in the mouse testis.

Materials and methods: Male mice underwent efferent duct transection and were analyzed at five time points up to 20 weeks. A three-dimensional reconstruction of serial testis sections was employed to visualize and quantitate impaired spermatogenesis in the seminiferous tubules.

Results: The volumes of the testis, seminiferous tubules, and interstitium showed 2-3-fold increases 1 week post-transection, but normalized by 5 weeks. The volume of the rete testis continued to increase, and was 9.3-fold larger by 20 weeks. The impairment of spermatogenesis in the seminiferous epithelium was progressive until 20 weeks. Three-dimensional mapping revealed marked spatial heterogeneity in impaired spermatogenesis: cranial seminiferous tubules remained highly viable, while the majority of caudal tubules were impaired. Furthermore, areas of severe impairment were identified in tubule regions near the rete testis in all tubules.

Discussion and conclusions: The present results suggest that chronic obstructive stress, driven by mechanical stress and/or local ischemia, is dominant in the caudal region and near the rete testis of the mouse testis. This study established a crucial link between obstructive azoospermia and a pathology resembling non-obstructive azoospermia, underscoring the importance of evaluating such spatial vulnerability in the clinical management of obstructive male infertility.

Objective: To evaluate the associations between advanced parental age and perinatal risks in twins.

Methods: We analyzed 7514 twin pairs conceived through in vitro fertilization. The exposure was advanced parental age (≥ 35 years), analyzed separately for mothers and fathers. Primary outcomes included birth weight discordance, small for gestational age, large for gestational age, macrosomia, low birth weight, very low birth weight, preterm birth, very preterm birth, and extremely preterm birth. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression. Additionally, parental age was analyzed both as a categorical variable and with a restricted cubic spline. The combined effect of advanced age in both parents was further evaluated.

Results: Advanced paternal age (≥ 35 years) was associated with increased odds of birth weight discordance (adjusted OR, 1.20; 95% CI, 1.01-1.42). A graded dose-response association was evident (p for trend = 0.026), with adjusted ORs for birth weight discordance progressively increasing across paternal age categories: 1.02 (95% CI, 0.83-1.25) for ages 30-34, 1.18 (95% CI, 0.91-1.52) for ages 35-39, and 1.41 (95% CI, 1.02-1.96) for ages ≥ 40 years, all compared to the < 30 years reference group. Restricted cubic spline analysis identified 37 years as a threshold beyond which paternal age significantly elevated birth weight discordance risk. Similarly, advanced maternal age (≥ 35 years) was significantly associated with increased small for gestational age odds (adjusted OR, 1.21; 95% CI, 1.04-1.41), with a significant trend (p for trend = 0.012) and a restricted cubic spline-derived threshold at 30 years. When both parents were over 35, the odds of birth weight discordance (adjusted OR, 1.37; 95% CI, 1.15-1.63) and small for gestational age (adjusted OR, 1.30; 95% CI, 1.13-1.50) were significantly elevated compared to both being under 35.

Conclusions: Advanced parental age was associated with elevated risks of birth weight discordance and small for gestational age in twins, suggesting it as a contributing factor to perinatal risk.

Testicular germ cell tumors (TGCT) are the leading malignancy in adolescent and young adult males, yet the immunological and cellular mechanisms governing their tumor microenvironment (TME) remain poorly understood. Here, we present a comprehensive review of TGCT pathobiology with a focus on the immune landscape, particularly the role of tumor-infiltrating T lymphocytes. The mammalian testis represents an immune-privileged organ maintained by the coordinated actions of somatic cells (Sertoli and Leydig cells) and resident immune populations that collectively foster immune tolerance and suppress deleterious inflammatory responses. Immune privilege is disrupted in TGCT, resulting in significant alterations in the composition and function of immune cell subsets such as macrophages, mast cells, dendritic cells, and especially T cells. The phenotypic diversity and functional adaptability of CD4⁺ T cell subsets (Th1, Th2, Th9, Th17, Th22, Treg, and Tfh) along with CD8⁺ T cell subsets (Tc1, Tc2, Tc9, Tc17, and Tc22) are critically evaluated in terms of their roles in anti-tumor immune responses, modulating immune regulation, and enabling tumor immune evasion within the TME of TGCT. Despite the success of immunotherapies such as immune checkpoint inhibitors targeting PD-1/PD-L1 and CTLA4, and emerging CAR-T cell strategies in other malignancies, their efficacy in TGCT is limited due to the unique testicular immune milieu and limited understanding of T cell dynamics in TME. Recent advances in single-cell transcriptomics and clinical studies highlight the necessity for high-resolution characterization of T cell subpopulations and their intercellular interactions within the TGCT TME. Elucidating these mechanisms is critical for the rational development of novel immunotherapeutic strategies aimed at overcoming resistance, minimizing long-term treatment-related sequelae, and enhancing clinical outcomes for TGCT patients.

Background: Poor sleep quality is associated with erectile dysfunction (ED), but the underlying mechanisms remain unclear. Given that systemic inflammation and testosterone levels are key factors in vascular health, this study investigates whether inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], neutrophil-to-lymphocyte ratio [NLR], and platelet-to-lymphocyte ratio [PLR]) and total testosterone (TT) mediate the relationship between sleep quality and erectile function in vasculogenic ED patients.

Methods: A total of 167 vasculogenic ED patients and 112 age-matched controls were recruited. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), and erectile function was evaluated using the International Index of Erectile Function-5 (IIEF-5). Inflammatory biomarkers and TT levels were measured, and principal component analysis (PCA) was applied to derive an inflammatory load score. Serial mediation analysis (PROCESS Model 6) was performed to examine whether inflammation and testosterone mediate the effect of sleep quality on erectile function, adjusting for potential confounders, including age, body mass index (BMI), smoking, triglycerides (TG), and total cholesterol (TC).

Results: Patients with vasculogenic ED had poorer sleep quality (p < 0.001), lower TT levels (p < 0.01), and higher inflammatory biomarker levels (p < 0.01) than controls. Correlation analysis showed PSQI was positively correlated with inflammation (β = 0.371, p < 0.001) and negatively correlated with TT (β = -0.206, p < 0.01) and IIEF-5 (r = -0.437, p < 0.001). Mediation analysis revealed: Inflammatory biomarkers (hs-CRP, IL-6, NLR, and PLR) significantly mediated the association between sleep quality and ED, with hs-CRP showing the highest effect (β = -0.133, p < 0.001), accounting for 21.73% of the total effect. Testosterone also played a mediating role (β = -0.055, p < 0.01), contributing to 8.99% of the total effect. After combining inflammatory biomarkers into a PCA-derived score, the mediation effect of inflammation increased to 38.60%, whereas the testosterone pathway weakened.

Conclusions: This study provides novel evidence that inflammation is a key mediator linking poor sleep quality to vasculogenic ED, while decreased testosterone levels play a secondary but still significant role.

Background: Nuts are rich in antioxidants and other bioactive compounds, and recent evidence suggests that their regular consumption may be associated with sperm quality. However, the current scientific evidence remains limited and inconsistent.

Objective: The study aimed to evaluate the association between nut consumption and sperm quality parameters in healthy men of reproductive age.

Materials and methods: A cross-sectional analysis was conducted using the data from 222 young men enrolled in the Led-Fertyl study. Nut consumption was categorized as < 3, ≥ 3 to < 7, and ≥ 7 servings/week (1 serving = 30 g). The main outcomes were sperm quality parameters (sperm count, concentration, vitality, motility, and normal morphology). Multivariate linear and logistic regression models were fitted to analyze associations.

Results: Total sperm count (β = 3.38; 95%CI: 1.59, 5.16) and concentration (β = 1.17; 95%CI: 0.15, 2.19) were higher among participants in the highest category of nut consumption (≥7 servings/week) compared to those in the lowest (< 3 servings/week). A similar association was observed when modeling nut consumption as continuous; each additional serving per day was associated with higher total sperm count and concentration (β = 2.38; 95%CI: 1.03, 3.72 and β = 0.83; 95%CI: 0.06, 1.59, respectively). A theoretical substitution of 1 serving/day of nuts with 1 serving/day of potato chips or pastries was associated with lower total sperm count and concentration. Furthermore, compared to participants in the lowest category of nut consumption, those in the highest were 75% less likely to have abnormal sperm motility (OR: 0.25; 95%CI: 0.07, 0.95) and 69% less likely to have seminogram abnormalities (OR: 0.31; 95%CI: 0.14, 0.68).

Conclusions: Our findings suggest that regular nut consumption is associated with higher total sperm count and concentration in young, healthy men of reproductive age.

Background: Men undergoing androgen deprivation therapy (ADT) for prostate cancer experience various adverse effects. Those with higher pre-treatment testosterone levels often express concerns about experiencing increased severity of these side effects, but this association has not been studied previously.

Objectives: The aim of this study was to assess the association of pre-treatment testosterone levels with changes in body composition, physical function, sexual function, and energy in men undergoing 24 weeks of ADT.

Materials and methods: Thirty-nine men were assessed at baseline and after 24 weeks of ADT. Body composition was assessed using dual-energy x-ray absorptiometry. Energy and vitality were evaluated using the Hypogonadism Energy Diary, and sexual function was assessed using the Sexual Arousal, Interest, and Drive scale. Physical function was assessed using the PF-10 subscale of the Short Form-36 Health Survey. Total and free testosterone levels were measured using liquid chromatography-tandem mass spectrometry and equilibrium dialysis, respectively. The association between pre-treatment testosterone levels and variables of interest was tested using linear regression analysis.

Results and discussion: At 24 weeks, the mean serum total testosterone level declined from 471 ± 157 to 7.7 ± 4.5 ng/dL, total fat mass increased by 3.7 kg (p < 0.0001), and total lean mass decreased by 2.2 kg (p < 0.0001). Participants experienced a decline in physical function, overall energy, and sexual desire. Pre-treatment testosterone levels were not associated with the magnitude of worsening in any of these outcomes.

Conclusion: Severity of adverse effects of ADT is not influenced by pre-treatment testosterone levels. This finding allows clinicians and patients to make informed decisions regarding treatment.

Background: Infertility is a pressing global health concern, affecting one in six couples worldwide. The failure rate for assisted reproductive technologies (ART) cycles remains at approximately 78%, with limited improvements often attributed to a lack of technological innovation. Sperm processing, a crucial component of ART success and offspring health, has seen minimal technical advancement, and current "gold-standard" methods such as density gradient centrifugation (DGC) carry risks of iatrogenic injury and DNA damage.

Objectives: Microfluidic sperm selection technologies have shown promise in leveraging sperm's unique motility behaviors by mimicking the female reproductive tract's microarchitecture.

Methods: In this study, we introduce a microfluidic ICSI (MICSI) platform by integrating microfluidic technology into the form factor of commercially available ICSI dishes, to integrate semen processing, motility and hyaluronic acid (HA) binding-based sperm selection, and oocyte insemination capacity on one single-use consumable. Sperm DNA fragmentation index (DFI), motility, binding score, and sperm morphology were measured to evaluate the performance of the MICSI device compared to DGC and DGC plus HA binding.

Results: Practically, the MICSI device was able to select a population of spermatozoa from raw semen with higher progressive motility (p < 0.0001), better morphology (p < 0.0001), and lower DFI (p < 0.0001). When compared to the conventional DGC, the MICSI device produced spermatozoa with significantly higher progressive motility (p < 0.0001) and lower DFI (p < 0.0001).

Discussion and conclusion: This data show that the MICSI device may offer a clinically applicable alternative for both selecting high-quality sperm for injection into oocytes and providing a platform to do so.

Background: Approximately one-fourth of patients with clinical stage I testicular cancer relapse. For decades, risk stratification has been based on different tumor characteristics for seminomas and non-seminomas. Previous studies primarily used Cox proportional-hazards models and included only a limited number of variables. Machine learning techniques can integrate large datasets and may uncover novel combinations of risk factors.

Objectives: To develop and validate a unified machine learning-based relapse prediction model for clinical stage I testicular cancer, regardless of histologic subtype, using nationwide histopathological and clinical data.

Materials and methods: A population-based cohort study of 1377 patients diagnosed with clinical stage I testicular cancer in Denmark from 2013 to 2018. Histopathological and clinical data were obtained through centralized pathology assessment and systematic medical record review. Two tree-based binary classifiers (CatBoost and LightGBM) were trained to predict relapse, and a random survival forest model was used to estimate time-to-relapse. Data were split into training (80%, 5-fold cross-validation) and a test set (20%), balanced by seminoma/non-seminoma subtypes and outcome. Subgroup analyses were performed for seminoma and non-seminoma. Binary models were evaluated using receiver operating characteristic area under the curve, precision-recall area under the curve, and Matthew's correlation coefficient; random survival forest performance was assessed using concordance index and Integrated Brier Score.

Results: CatBoost outperformed LightGBM (receiver operating characteristic area under the curve = 0.74) and demonstrated a high negative predictive value (0.86). The random survival forest achieved a concordance index of 0.71. Predictive performance was stronger in the non-seminoma than in the seminoma subgroups. Top-ranked predictive features included lymphovascular invasion, embryonal carcinoma, tumor necrosis, rete testis invasion, tumor size, and elevated lactate dehydrogenase and β-human chorionic gonadotropin. Tumor necrosis and the anatomical location of lymphovascular invasion emerged as novel predictors.

Discussion and conclusion: A unified machine learning-based model for relapse prediction in clinical stage I testicular cancer is feasible and demonstrates moderate predictive accuracy. It is particularly useful for ruling out relapse and shows greater robustness in non-seminoma. These findings provide a framework for validation in independent cohorts and highlight key predictive features for future research.

Background: Spermatozoa undergo protein modifications due to oxidative stress as a result of freezing-thawing. With increasing information on oxidatively modified proteins of frozen-thawed spermatozoa, it is essential to investigate the effect of supplementing the semen extender with the repair enzyme protein L-isoaspartyl methyltransferase (PIMT) on the quality of frozen-thawed spermatozoa.

Objectives: To investigate the expression of PIMT in male reproductive organs, including semen, and to evaluate the effect of recombinant PIMT (rPIMT) supplementation on the quality of frozen-thawed spermatozoa.

Materials and methods: Expression of PIMT was studied using immunofluorescence assays, PCR, and Western blotting. Functionalities of spermatozoa were studied by HOST, viability, progressive motility, acrosome intactness, and zona-binding assays.

Results: The PIMT was detected all along the male reproductive tract, including spermatozoa, but could not be detected in the seminal plasma. The rPIMT was added to the extender at 0.5 (Group II), 1.0 (Group III), and 2.0 µg/80 million spermatozoa (Group IV), with the control (Group I) receiving no rPIMT. A significant effect was observed in Group IV, with an 8.9% increase in progressive motility, a 13.0% increase in viability, an 11.9% increase in HOST response, and an 11.8% improvement in acrosome integrity compared with the control. Further, motility and kinematic parameters (VCL, VAP, DSL, VSL, DAP, ALH, and BCF) of frozen-thawed spermatozoa were assessed using CASA. Most motion parameters were higher in group IV compared with the I, II, and III groups. Additionally, the in vitro fertilizability of Group IV spermatozoa was approximately 2.32 times higher compared with the control group.

Discussion and conclusion: The better functional attributes and a fold increase in fertilizability of frozen-thawed spermatozoa positively correlate with the quality of spermatozoa. It may be presumed that the rPIMT improved the cryopreserved semen quality through the repair of oxidatively damaged seminal plasma proteins.