Andrology最新文献

Background: Sexual position is one of the several aspects that affects ejaculation control, which is essential for sexual pleasure. Still little is known, nevertheless, about the connection between sexual positions and ejaculation duration.

Objective: To investigate the impact of various sexual positions on the duration of ejaculation and gain a deeper understanding of the elements that influence the ability to control ejaculation.

Method: An online survey was carried out on a sample of 1904 heterosexual men between the ages of 18-65 years. Premature ejaculation (PE) diagnostic tool was used to define PE. Demographic, behavioral, and physiological traits that are linked to PE and non-PE groups were collected. The participants listed their preferred sexual positions and the ones they changed to during ejaculating. Also, analyses were performed between male/female active or deep/shallow thrust positions and PE status.

Results: Although there were no appreciable variations in age or circumcision between PE and non-PE groups, the age of first sexual experience was associated with PE status. Groups also varied in the number of weekly ejaculations, the duration of the favored ejaculations, and the characteristics of the erection. The most preferred sexual posture was the doggy style regardless of the group. When the non-PE group felt to ejaculate, they preferred to change the position significantly more than the PE group (74% vs 67.2%; p < 0.05). However, when participants felt ejaculate, non-PE participants tended to switch to shallow thrusting positions significantly more than PE participants, who preferred deeper positions (27.1% vs. 18%; p < 0.05).

Conclusion: This study underlines the relevance of considering sexual positions in controlling PE. Modifying positions during sexual intercourse may offer a non-pharmacological therapeutic alternative for improving ejaculation control. Future studies in this field might help to create tailored PE treatment strategies.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus caused the coronavirus disease 2019 pandemic, and the prevalence of deaths among men is higher than among women. The epididymis, divided into caput, corpus, and cauda, shows a region-specific immunity. The K18-hACE2 mouse expresses human angiotensin-converting enzyme 2 (hACE2), the receptor that allows SARS-CoV-2 infection. However, studies using this transgenic mouse to evaluate the impact of this viral infection in epididymis have not yet been performed.

Objectives: We evaluated the expression of hACE2 in the epididymis of SARS-CoV-2-infected K18-hACE2 mice, and assessed the epididymal immune response, focusing on F4/80⁺ mononuclear phagocytes and tumor necrosis factor-alpha expression.

Materials and methods: The following analyses were performed in the epididymal sections of infected mice: epithelial height and duct diameter, birefringent collagen, Terminal deoxynucleotidyl Transferase-mediated dUTP Nick End Labelling, immunoreactions for detection of hACE2, spike, FGF, V-ATPase, F4/80, tumor necrosis factor-alpha, and iNOS. Viral particles were identified under electron microscopy. hACE2, Rigi, Tgfb1 and Tnfa expression were also evaluated by real-time quantitative polymerase chain reaction.

Results: All epididymal regions expressed hACE2, which increased in all epididymal regions in the infected mice. However, the caput appeared to be the most infected region. Despite this, the caput region showed minimal changes while the cauda showed significant epithelial changes associated with increased iNOS immunoexpression. The F4/80⁺ mononuclear phagocyte area increased significantly in both stroma and epithelium. In addition to the epithelial and stromal mononuclear phagocytes, tumor necrosis factor-alpha was also detected in clear cells, whose cytoplasm showed a significant increase of this cytokine in the infected animals.

Discussion and conclusion: The K18-hACE2 mouse is a useful model for evaluating the impact of SARS-CoV-2 infection in the epididymis. The infection induced hACE2 upregulation, favoring the virulence in the epididymis. The epididymal regions responded differentially to infection, and the activation of F4/80⁺ mononuclear phagocytes associated with the increased tumor necrosis factor-alpha immunolabeling in clear cells indicates a role of clear cells/mononuclear phagocytes immunoregulatory mechanisms in the epididymal immune response to SARS-CoV-2 infection.

Background: The PWWP domain-containing proteins are involved in chromatin-associated biological processes, including transcriptional regulation and DNA repair, and most of them are significant for gametogenesis and early embryonic development in mammals. PWWP3A, one of the PWWP domain proteins, is a reader of H3K36me2/H3K36me3 and a response factor to DNA damage. However, the physiological role of PWWP3A in spermatogenesis and fertility remains unclear.

Objective: The goal of this study was to explore the function and mechanism of PWWP3A in the process of spermatogenesis.

Materials and methods: We generated V5-Pwwp3a KI mice and PWWP3A polyclonal antibody to observe the localization of PWWP3A in vivo. Meanwhile, Pwwp3a KO mice was used to explore the function in spermatogenesis.

Results: We reported that PWWP3A is a predominant expression in the testis of mice. During spermatogenesis, PWWP3A exhibits the temporal expression from early-pachytene to the round spermatids. The results of spermatocyte spreading and immunostaining showed that PWWP3A aggregated on the XY body, which then diffused as the XY chromosome separated at late-diplotene. Although the depletion of PWWP3A had no obvious reproductive defects in young male mice, there were observed morphological abnormalities in sperm heads. Immunoprecipitation demonstrated the interaction of PWWP3A with DNA repair proteins SMC5/6; however, PWWP3A deficiency did not result in any meiotic defects. Notably, the testes of aged male Pwwp3a KO mice displayed pronounced degeneration, and were characterized by the presence of vacuolated seminiferous tubules. Furthermore, RNA-seq analysis revealed an upregulation in the expression of genes which may be involving in immunoregulatory and inflammatory response pathways in aged Pwwp3a KO mice with testicular degeneration.

Conclusions: Our study showed that PWWP3A was highly enriched in the mouse testis, and the Pwwp3a KO mice were fertile. However, the aged Pwwp3a KO male mice displayed testicular atrophy that may be due to changes in the immune micro-environment or abnormal repair of DNA damage.

Background: Varicocoele is a correctable cause of male infertility. Although physical examination is still being used in diagnosis and grading, it gives conflicting results when compared to ultrasonography-based varicocoele grading.

Objectives: We aimed to develop a multi-class machine learning model for the grading of varicocoeles based on ultrasonographic measurements.

Method: Between January and May 2024, we enrolled unilateral varicocoele patients at an infertility clinic, assessing their varicocoele stages using the Dubin and Amelar system. We measured vascular diameter and reflux time at the testicular apex and the subinguinal region ultrasonography in both the supine and standing positions. Using these measurements, we developed four multi-class machine learning models, evaluating their performance metrics and determining which patient position and projection were most influential in varicocoele grading.

Results: We included 248 patients with unilateral varicocoele in the study, their average age was 26.61 ± 4.95 years old. Of these, 212 had left-sided and 36 had right-sided varicocoeles. According to the Dubin and Amelar system, there were 66 grade I, 96 grade II, and 86 grade III varicocoeles. Among the models we created, the random forest (RF) model performed best, with an overall accuracy of 0.81 ± 0.06, an F1 score of 0.79 ± 0.02, a sensitivity of 0.69 ± 0.02, and a specificity of 0.8 ± 0.03. Vascular diameter measurement at the testicular apex in the supine position had the most impact on grading across all models. In support vector machine and multi-layer perceptron models, reflux time measurements from the subinguinal projection in the standing position contributed the most, while in RF and k-nearest neighbors models, measurements from the subinguinal projection in the supine position were the most influential.

Conclusions: Machine learning methods have demonstrated superior accuracy in predicting disease compared to traditional statistical regressions and nomograms. These advancements hold promise for clinically automated prediction of varicocoele grades in patients. Tailored varicocoele grading for individuals has the potential to enhance treatment effectiveness and overall quality of life.

Introduction: Antidepressants may lead to a series of sexual adverse effects (SAEs), among which ejaculation dysfunction (EjD) is often overlooked by clinicians. The purpose of the present network meta-analysis was to assist drug adjustment by comparing and ranking the incidence of EjD among various antidepressants.

Methods: Relevant studies were retrieved from PubMed, Embase, Scopus, Web of Science, ClinicalTrials.gov, and other additional records. Eligible randomized controlled trials (RCTs) assessed the rate of EjD in patients with major depressive disorder (MDD) and anxiety disorder after taking anti-depressants. The incidences of EjD, erectile dysfunction (ED), decreased libido (DL), adverse events (AE), withdrawal due to adverse events (WDAE) and withdrawal due to lack of efficacy (WDLE) were pooled using odds ratio (OR) with their 95% confidence intervals (CI). The values of surface under the cumulative ranking curve (SUCRA) helped to rank the risk of each outcome in different antidepressants.

Results: Thirty RCTs comprising 18,157 patients were included. Results of all node-splitting analysis demonstrated no statistical inconsistency (all P > 0.05). Clomipramine (OR 42.11, 95% CI [9.90, 179.08]), WS5570 (OR 28.99, 95% CI [1.48, 568.97]) and paroxetine (OR 18.63, 95% CI [9.33, 37.23]) had significant risk of EjD comparing to placebo. Additionally, duloxetine (OR 7.37, 95% CI [2.61, 20.78]), clomipramine (OR 5.29, 95% CI [1.72, 16.25]), paroxetine (OR 3.75, 95% CI [1.37, 10.26]) and escitalopram (OR 3.04, 95% CI [1.20, 7.71]) presented higher risk of ED comparing to placebo. Agomelatine, levomilnacipran, vortioxetine, trazodone, vilazodone, fluvoxamine and imipramine exhibited similar incidence of EjD with placebo (all P > 0.05). Besides, trazodone, vilazodone and vortioxetine had the top-five SUCRA values in each of SAEs (EjD, ED and DL), and agomelatine might be alternative in EjD and DL. Considering about AE, WDAE and WDLE, vilazodone appeared to offer more satisfactory performance across all these aspects.

Conclusions: For patients undergoing SAEs following the administration of antidepressants, trazodone, vortioxetine, vilazodone and agomelatine are alternative antidepressants.

Introduction: There is inconsistent data regarding the possible inaccuracies in dynamic penile color Doppler duplex ultrasound (CDDU) measurements in men with penile curvature because of Peyronie's disease (PD). We sought to explore the relationship between the degree of penile curvature and CDDU parameters in men with PD.

Materials and methods: Comprehensive data from 154 consecutive men presenting with PD as their primary complaint at a single academic center were prospectively collected and analyzed. All men underwent CDDU. Penile curvature was measured using a goniometer at time of maximum erection during CDDU. Patients were grouped based on CDDU parameters into-normal (average peak systolic velocity [PSV] ≥ 35 cm/s and resistance index [RI] ≥ 0.85) and pathological CDDU (average PSV < 35 cm/s and/or RI < 0.85). Descriptive statistics was used to compare the two subcohorts. Linear regression models were fitted to explore the association between the degree of penile curvature and dynamic CDDU parameters.

Results: Overall, the median interquartile range (IQR) age was 56 (48-63) years. The median (IQR) PSV and degree of penile curvature were 48.8 cm/s (37.9-58.5) and 40 degrees (30-60), respectively. At CDDU, the degrees of penile curvature were as follows: 10-30 degrees in 63 (40.9%) men, 30-70 degrees in 70 (45.5%) men, and 70-90 degrees in 21 (13.6%) men, respectively. Of all, 116 (75.3%) patients showed a PSV > 35 cm/s and RI ≥ 0.85. Patients with pathologic vs. normal CDDU parameters did not differ in median (IQR) curvature (32.5° [30°-58.7°] vs. 40° [30°-65°], p = 0.5) or in the distribution across curvature range groups. Linear regression analysis revealed that the degree of penile curvature did not significantly correlate with PSV at CDDU (coefficient: 0.06, p = 0.3).

Conclusions: Our study confirms the lack of a significant correlation between the severity of penile curvature and CDDU parameters in men presenting with PD. These findings emerge to be relevant in terms of a more accurate management work-up for PD patients and hold insightful medicolegal implications and in the real-life setting.

Background: Ascorbic acid 2-glucoside (AA2G) is a stabilized form of ascorbic acid and a potent antioxidant. Ascorbic acid is present in the testes and epididymis and helps maintain the physiological integrity of reproductive organs. Its properties have been utilized to protect spermatozoa of different species from oxidative stress.

Materials and methods: Spermatozoa of C57Bl/6J and C57Bl/6N strains were frozen and analyzed, after thawing, by supplementing the capacitation medium with AA2G, both in the presence and absence of methyl-β-cyclodextrin (MBCD). The effect of treatment was evaluated by SCA System (Microptic) analyzing the velocity, vitality, morphology, and the DNA fragmentation. We also examined sperm capacitation (CTC), acrosome reaction (Coomassie Brillant Blue), and fertility (in vitro fertilization) of treated spermatozoa.

Results: AA2G improved sperm quality and fertility particularly in association with MBCD. We observed a significant increase of sperm motility, velocity, and vitality associated with an enhanced capacitation and acrosome reaction. These improvements resulted in a marked increase in in vitro fertilization success. Embryos obtained were cultured and reached normally the blastocyst stage.

Discussion: This study aimed to determine if AA2G could safeguard mouse spermatozoa during cryopreservation. We found a protective effect of AA2G that increased sperm survivability resulting in higher fertilization rate.

Conclusion: This newly improved protocol shows potential for reanimating cryopreserved GEMMs stored in mouse biobanks and international repositories, such as the European Mouse Mutant Archive (EMMA). This can serve as a pivotal tool in fulfilling the 3Rs mission (replacement, reduction, and refinement), promoting ethical and humane research practices.

Testicular fibrosis is a chronic and progressive condition characterized by the excessive deposition of extracellular matrix proteins. This process leads to fibrotic remodeling, damage to testicular tissue, and the irreversible loss of male reproductive function. However, there is currently a lack of comprehensive reviews systematically elucidating the pathology, diagnosis, pathogenesis, and treatment of testicular fibrosis from the perspectives of different related diseases. This review addresses these aspects of testicular fibrosis, with a particular emphasis on elucidating the underlying mechanisms of testicular cells. It provides insights that can be relevant for future research and clinical interventions.

Background: HENMT1 encodes a small RNA methyltransferase that plays a crucial role in mouse spermatogenesis through the methylation of the 3' end of PIWI-interacting RNAs.

Objectives: Our study aims to elucidate the relationship between HENMT1 and male infertility in humans.

Materials and methods: A consanguineous family, having a single non-obstructive azoospermia patient was recruited for pathogenic variants screening. The research includes genetic analysis and experimental validation using mouse models. The patient was diagnosed with non-obstructive azoospermia. Whole-exome sequencing and subsequent bioinformatic analyses were performed to screen for candidate pathogenic variants. The pathogenicity of the identified variant was assessed and studied in vivo using a mouse model that mimicked the patient's mutation.

Results: Through whole-exome sequencing, we identified a homozygous nonsense variant (c.555G > A, p.Trp185*) in HENMT1 in the patient. The presence of the mutant HENMT1 mRNA was detected in the patient's blood, and the truncated HENMT1 protein was observed in transfected HEK293T cells. The mutant mice modeling this HENMT1 variant displayed an infertile phenotype similar to that of the patient, characterized by spermiogenesis arrest. Further analysis revealed a significant derepression of retrotransposon LINE1 in the testes of the Henmt1 mutant mice, and increased apoptosis of spermatids.

Discussion and conclusion: Our findings provide the evidence of pathogenicity of the identified HENMT1 variant, thus shedding light on the indispensable role of HENMT1 in human spermatogenesis.