Andrology最新文献

Background: Low parental education is associated with poorer offspring health, but its influence on male fecundity remains unclear.

Objective: To study the association between parental educational attainment at birth and biomarkers of male fecundity in young men and to explore whether this association is mediated by maternal smoking in pregnancy and overweight/obesity at 19 years of age.

Materials and methods: A cohort study with 1058 sons born 1997-1999 from the Fetal Programming of Semen Quality (FEPOS). The exposure was the highest educational attainment among parents at their child's birth, obtained from administrative registers. Outcomes were measured at a clinical examination and included semen characteristics (semen volume, semen concentration, total sperm count, motility, morphology, DNA fragmentation index, and high DNA stainability), testicular volume, and reproductive hormone levels (estradiol, testosterone, Sex Hormone-Binding Globulin, luteinizing hormone, and follicle-stimulating hormone). Outcomes were analyzed using a multivariable negative binomial regression model adjusted for potential confounding factors and precision variables. Potential mediation by maternal smoking in pregnancy, as well as overweight or obesity at 19 years of age, was investigated in separate mediation analyses.

Results: Sons of parents with low educational attainment at birth had a tendency to have lower semen volume (relative percentage difference: -8% (95% confidence interval [CI]: -17%; 2%), lower semen concentration (-8% [95% CI: -20%; 6%]) and lower total sperm count (-12% [95% CI: -25%; 3%]) compared to sons of parents with high educational attainment. No major difference was observed for other biomarkers of male fecundity. Maternal smoking in pregnancy, but not overweight/obesity at 19 years of age, partly mediated the association.

Conclusion: Our findings suggest some association between parental educational attainment and biomarkers of male fecundity in young men. These findings were partly mediated by maternal smoking in pregnancy, but not by overweight or obesity in young adult sons.

Background: Postprandial lipid testing is increasingly recognized as a marker of vascular health. However, its relationship with erectile dysfunction (ED) remains largely unexplored. Isolated postprandial dyslipidemia (IPD), in particular, may evade detection using conventional fasting-based assessments, despite potential atherogenic effects.

Objectives: To evaluate the association between IPD and erectile function, comparing the prevalence and severity of ED among men with IPD, combined dyslipidemia (CD), and those without dyslipidemia (WD).

Materials and methods: In this cross-sectional study, sexually active men aged ≥18 years underwent same-day fasting and postprandial lipid testing, as well as erectile function evaluation using the International Index of Erectile Function - Erectile Function domain (IIEF-EF) questionnaire. Dyslipidemia was defined according to the 2019 European Society of Cardiology/European Atherosclerosis Society criteria. Patients were categorized as WD (no dyslipidemia), IPD (postprandial abnormalities only), or CD (both fasting and postprandial abnormalities). Multivariable logistic regression was performed, adjusting for age, smoking status, BMI, and hypertension. The primary outcome was the prevalence of ED (IIEF-EF ≤25); secondary outcomes included ED severity and comparisons across lipid profile subgroups.

Results: Among 351 men, ED prevalence was higher in the IPD (55.1%) and CD (57.0%) groups compared to WD (32.8%; p < 0.001). Median (IQR) IIEF-EF scores were 26 (25-28) in the WD group, 22 (20-23) in the IPD group, and 21 (19-23) in the CD group. The differences between WD and both IPD and CD exceeded the minimal clinically important difference (4 points) and were statistically significant (p < 0.001). Adjusted analyses confirmed increased odds of ED in IPD (odds ratio [OR] = 2.36; 95% confidence interval [CI]: 1.41-3.96) and CD (OR = 2.58; 95% CI: 1.43-4.65) versus WD. ED severity was also greater in the IPD and CD groups. No differences emerged between IPD and CD in any outcome. Among IPD subtypes, elevated postprandial triglycerides were most common, but no single lipid abnormality was independently associated with ED severity.

Conclusion: IPD is associated with both the prevalence and severity of ED, paralleling the impact of chronic dyslipidemia. Postprandial lipid testing may reveal hidden metabolic risks relevant to sexual health and should be considered in the evaluation of ED.

Background: The Testicular Cancer Consortium (TECAC) was established in 2012 and is comprised of researchers from over 25 centers in Europe and North America. TECAC's overarching goal is to investigate the genetic susceptibility of testicular germ cell tumors (TGCT) to better understand their biology, impact prevention strategies, and inform treatment decisions.

Objectives: To provide an overview of TECAC genetic and phenotypic holdings.

Materials and methods: TECAC has composed by-laws describing the consortium structure and governance, codified the processes for manuscript development and data transfer, and developed guidance for the transfer of biological samples and access to data.

Results: TECAC has assembled a vast amount of genetic information on males with TGCT-including SNP-array data on over 13,500 cases, whole-exome sequencing data on over 4500 cases, and low-pass whole-genome sequence data on over 2700 cases. Genetic information on males without TGCT (controls) is derived from studies designed to assess risk factors for TGCT and from publicly available resources. When available, corresponding phenotypic information is collected and harmonized. Fifteen publications have resulted from genetic and phenotypic information curated by TECAC.

Discussion: The sharing of genetic and phenotypic data by TECAC centers to inform large studies of TGCT susceptibility has led to novel insights into the genetic architecture of this cancer, including the roles of genes involved in male germ cell development, sex determination, chromosomal segregation, and RNA transcription. These findings would not have been achievable by individual centers or smaller collaborative efforts.

Conclusion: We invite investigators from any discipline who have access to collections of germline DNA, somatic cell DNA, or genomic information on males with TGCT to consider joining TECAC to further strengthen our efforts to reduce the global burden of TGCT.

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: 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.