Andrology最新文献

Background: Study aimed to obtain insights into physiological responses to immunocastration in pubertal boars by evaluating effects of alternative vaccination protocols and identifying a reliable immunocastration biomarker.

Objectives: It was hypothesized that the timing of gonadotropin-releasing hormone (GnRH) suppression by immunocastration differentially affects reproductive function, as reflected by testicular histology and expression of selected genes related to testicular function, steroid metabolism, and Leydig cell differentiation and function.

Materials and methods: Effects of three vaccination protocols on antibody titers, testicular histomorphology, and mRNA expression in immunocastrates slaughtered 4, 8, or 12 weeks (IC-4, IC-8, and IC-12, respectively; n = 6 per group) after booster were compared with entire males (EMs; n = 6). Principal component analysis and hierarchical clustering were used to evaluate individual responses and to identify an immunocastration biomarker(s). The selected biomarker was also validated on samples from previous studies.

Results: All immunocastrated boars reacted immunologically to vaccination (increased GnRH antibody titer; p < 0.004). There was an increased nucleus-to-cytoplasm ratio in Leydig cells (p < 0.033) and decreased testosterone concentration (p < 0.041) in IC-4 compared with EM, whereas values in IC-8 and IC-12 were intermediate. Hierarchical clustering differentiated immunocastrates with low testosterone (IC-LT; median 0.56 ng/mL) and high testosterone (IC-HT; median 7.04 ng/mL). In IC-LT, expression levels of FSHR and ESR2 were higher than in IC-HT, and those of LHCGH, STAR and INSL3 were lower compared with IC-HT and EM, whereas expression of ESR1 and HSD17β7 was lower in IC-LT and IC-HT compared with EM (fold change > 1.5 and p < 0.05).

Conclusion: There were variable responses to immunocastration in pubertal boars subjected to three vaccination protocols. Suppression of testicular function was most pronounced in boars slaughtered 4 weeks after the booster, whereas progressive recovery occurred in some boars 8 and 12 weeks after the booster. Irrespective of vaccination protocol, INSL3 mRNA expression was a reliable immunocastration biomarker.

Erectile dysfunction (ED) diagnostics are in need of innovation, as traditional tools like the RigiScan face usability challenges and limited clinical adoption. Although several novel sensor systems have been proposed, none have undergone comprehensive clinical validation. This opinion article outlines a structured, three-phase validation framework comprising component validation, system feasibility testing, and clinical validation, aligned with European MDR requirements. Special attention is given to key aspects such as diagnostic accuracy, sleep-stage monitoring, and patient experience. By providing a clear validation pathway, this opinion article aims to support researchers in the development of reliable, patient-friendly, and regulatory-ready tools for non-invasive ED diagnosis.

Background: Androgen receptors are highly expressed in upper body muscles, but changes in maximal muscle strength and power in major upper body muscles have not been investigated during gender-affirming hormone therapy (GAHT).

Objective: To assess prospective changes in maximal muscle strength and muscle power from before and after 1 year of GAHT.

Design and methods: Clinical prospective study in 92 transgender persons: 26 transmasculine treatment-naïve (TransM_naïve), 27 transmasculine treatment-ongoing (TransM_ongoing), 29 transfeminine treatment-naïve (TransF_naïve), and 10 transfeminine treatment-ongoing (TransF_ongoing) were examined at baseline and after 1 year of GAHT. Primary outcomes were unilateral upper body maximal muscle strength (kg) and mean and maximal power (watt) measured by low-row dynamic testing. Dual-energy X-ray absorptiometry was conducted in all participants.

Results: In transmasculine persons, the median (quartiles) age was 22 (20; 30) years in TransM_naïve and 26 (22-29) years in TransM_ongoing (median GAHT duration 3 (2; 5) years) at study inclusion. Maximal muscle strength increased 6.3 kg (12%) in TransM_naïve (p ≤ 0.001) and 5.0 kg (7%) in TransM_ongoing (p ≤ 0.001), while maximal muscle power remained unchanged. ∆-muscle strength was positively associated with ∆-lean mass in arms and negatively associated with age at GAHT initiation. In transfeminine persons, the median age was 24 (22; 30) years in TransF_naïve and 40 (31-64) years in TransF_ongoing (median GAHT duration 4 (2; 6) years) at study inclusion. Maximal muscle strength decreased 17.5 kg (23%) in TransF_naïve and -5.0 kg (8%) in TransF_ongoing, which was accompanied by a decrease (23%) in maximal muscle power in TransF_naïve.

Conclusion: Upper body muscle strength but not power increased during masculinizing GAHT, whereas muscle strength and power decreased within the first year of feminizing GAHT.

Background: Although a nomogram for predicting the efficacy of dapoxetine (DapE-Nomo) has already been developed, its reliability is limited due to only 4 weeks of follow-up and a lack of external validation. Several patients with premature ejaculation (PE) achieve satisfactory therapeutic effects after longer periods of treatment clinically, we therefore aimed to develop and validate an 8-week DapE-Nomo.

Methods: The training cohort included 243 patients with lifelong PE from Xijing Hospital and Northwest Women's and Children's Hospital (Jan 2019-Jul 2020), while the validation cohort comprised 397 patients from Xijing Hospital and Xi'an Daxing Hospital (Aug 2020-Jan 2022). Efficacy was measured using the Clinical Global Impression of Change (CGIC) scale, with a CGIC score ≥ 1 indicating an improvement (iCGI). LASSO regression was utilized to identify the most valuable predictors (MVPs) of iCGI. The DapE-Nomo was developed utilizing logistic regression coefficients of MVPs and validated across both cohorts.

Results: After 8 weeks of medication, 47.7% of patients in the training cohort and 47.6% in the validation cohort achieved iCGI. MVPs of iCGI included intravaginal ejaculation latency time, difficulty delaying ejaculation, and education level. The DapE-Nomo showed discriminatory abilities of 0.722 and 0.709 in internal and external validations, respectively, with satisfactory calibration and clinical utility in both. The optimal cutoff value of the DapE-Nomo was identified as 153.4 in both cohorts. Individuals with scores ≥153.4 exhibited a 3.833-fold and 4.137-fold chance of achieving iCGI, respectively, compared with those with scores < 153.4.

Conclusion: We constructed and validated the inaugural 8-week DapE-Nomo. In outpatient settings, it will enable andrologists to more accurately evaluate the efficacy and promptly adjust treatment plans for patients with scores below 153.4. Moreover, It will help patients who've taken dapoxetine for 4 weeks with poor results decide whether to stop.

Background: Studies show that coenzyme Q10 (CoQ10) has multiple benefits for improving idiopathic male infertility. However, its protective effects against hypoxia-induced damage to the male reproductive system and varicocoele-associated spermatogenesis dysfunction need further investigation.

Objectives: This study aims to evaluate CoQ10's preventive efficacy against testicular damage caused by chronic hypoxia and varicocoele, and to explore the underlying mechanisms.

Materials and methods: Chronic hypoxia-induced and varicocoele male rat models were established. CoQ10 was administered intragastrically. Transcriptome analysis of testicular tissue, along with qRT-PCR and Western blot, was performed to elucidate mechanism and confirm gene and protein expression changes.

Results: The study revealed that both chronic hypoxia and varicocoele reduce sperm concentration, motility, vitality, and cause vacuolation of seminiferous tubules. Both conditions also lower reproductive hormone levels, increase oxidative stress, and promote germ cell apoptosis. CoQ10 treatment protected against these testicular changes and improved testosterone levels in rats. Seven differentially expressed genes (Slc38a5, Adgrg2, Gpc1, Arx, Egr2, Ebp, Il2rb) were identified in CoQ10-treated rats with either condition. Enrichment analysis highlighted inflammation as the main affected process in testes for both conditions. qRT-PCR and Western blot confirmed that CoQ10 significantly reduced IL1β, Egr2, Il2rb, and caspase-1 expression at both gene and protein levels.

Conclusion: These findings suggest that CoQ10 improves chronic hypoxia-induced and varicocoele-related spermatogenesis dysfunction by reducing inflammation via the caspase1-IL1β-egr2 pathway. The study highlights CoQ10's protective role in male reproduction and its potential for treating male infertility linked to hypoxia and varicocoele.

Background: The oxytocin receptor (OR) is a G-protein-coupled receptor recently identified in human spermatozoa, whose origin and role in sperm physiology remain unknown.

Objectives: In this study, using the pig as a model, we examine the presence of the OR in ejaculated spermatozoa through immunofluorescence and immunoblotting, and investigate the receptor's origin in the male gamete via immunohistochemistry in testicular and epididymal tissues. Additionally, we assess the involvement of the OR in in vitro capacitation and the acrosome reaction by utilizing physiological concentrations of agonists (oxytocin and carbetocin) and an antagonist (L-371,257).

Results: The results indicate that, in addition to the expected presence in ejaculated spermatozoa, the OR is expressed during spermatogenesis. Besides, this receptor is found in Leydig and Sertoli cells, as well as in the principal, basal, and apical cells of the epididymis. Furthermore, our data suggest that, during epididymal maturation, the OR could be incorporated in spermatozoa via extracellular vesicles within the apical blebs. The OR is involved in sperm capacitation, as the combination of the antagonist (L-371,257) and the agonist (carbetocin) increases intracellular calcium levels and membrane lipid disorders, which are known as capacitation markers.

Conclusions: The presence of the OR in mammalian spermatozoa could originate from both spermatogenesis and epididymal maturation. Moreover, in the male gamete, this receptor regulates sperm capacitation by interacting with its ligand in the female reproductive tract.