{"title":"Expression of IL-33 in rodent testes and its role in Leydig cell steroidogenesis and aging.","authors":"Hu Wang, Yun Hu, Zhenni Li, Enhui Wu, Qichao Yuan, Xinyu Niu, Jingwen Liu, Hanmin Cai, Mengjie Qin, Jingfeng Xu, Jiexia Wang, Xiaoju Guan, Haolin Chen, Congde Chen","doi":"10.1111/andr.70078","DOIUrl":"https://doi.org/10.1111/andr.70078","url":null,"abstract":"<p><strong>Background: </strong>Serum testosterone (T) concentration declines with aging in men, potentially affecting reproduction, mental and physical well-beings. A role of immune factors in Leydig cell (LC) function is well-known, but the specific factors involved, especially these playing roles in LC aging, are still unclear. This study investigated effects of interleukin 33 (IL-33) on LC function and its expression during testicular aging.</p><p><strong>Methods: </strong>Immunohistochemistry and Western blotting were used to determine IL-33 and its receptor IL1RL1 expressions in testes of young (3-month-old) and old (19-24-month-old) Wistar rats. In vitro, the effects of IL-33 on sex steroid hormone productions were evaluated in primary and MLTC-1 LCs over 2-24 h. Different steroidogenic stimulators or signaling molecules (luteinizing hormone [LH], 8-Br-cAMP, Forskolin, pertussis toxin, and MAPK activators) were compared with elucidate mechanisms. Steroidogenic pathway proteins and potential signaling molecules were explored by Western blotting.</p><p><strong>Results: </strong>IL-33 is expressed by mesenchymal cells, with the number increasing significantly with aging. IL1RL1, its receptor, is expressed by LCs and remains unchanged. In vitro, IL-33 acutely inhibited LC steroidogenesis in a dose-dependent manner (1-100 ng/mL) within 2-24 h. The effect was LH-dependent; replacing LH with either 8-Br-cAMP or Forskolin abolished the inhibition. IL-33 mainly affected STAR in the steroidogenic pathway. Signaling molecules involving STAR regulation (AKT and MAPK) were down-regulated while PKA phosphorylation was increased. P38 MAPK involvement was confirmed as increased Tyr182 phosphorylation of P38 by SB203580 partly reversed the IL-33-induced steroidogenesis inhibition.</p><p><strong>Conclusion: </strong>Testicular mesenchymal cells can synthesize IL-33, and LCs express the receptor IL1RL1. IL-33 inhibits LC steroidogenesis in vitro, partially via inhibiting P38 MAPK phosphorylation. As IL-33-expressing cell numbers rise significantly with aging, its role in age-related LC T production decline warrants further study.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AndrologyPub Date : 2025-06-15DOI: 10.1111/andr.70076
Ana Paula de Souza Kussler, Ivan Cunha Bustamante Filho, Elisa Negri, Edison Capp, Helena von Eye Corleta
{"title":"Oxidative stress markers and sperm structural integrity regarding semen processing methods followed by cryopreservation.","authors":"Ana Paula de Souza Kussler, Ivan Cunha Bustamante Filho, Elisa Negri, Edison Capp, Helena von Eye Corleta","doi":"10.1111/andr.70076","DOIUrl":"https://doi.org/10.1111/andr.70076","url":null,"abstract":"<p><strong>Background: </strong>Seminal cryopreservation causes significant sperm damage, prompting research into alternative preservation methods. This study aimed to compare the effects of washing and density gradient processing-both involving seminal plasma removal-on oxidative damage, acrosomal, and mitochondrial integrity.</p><p><strong>Materials and methods: </strong>Seminal samples from 26 normozoospermic patients were divided into three parts: one containing seminal plasma, the second processed by washing, and the third processed by selection through a density gradient. The samples were cryopreserved for at least 2 weeks. reactive oxygen species (ROS) production (measured using the DCF probe), plasma membrane peroxidation (BODIPY probe), acrosome integrity (fluorescein isothiocyanate-labeled/prostate-specific antigen [FITC/PSA] probe), lipid disorder (merocyanine 540 probe), and mitochondrial potential (JC1 probe) were evaluated through flow cytometry before cryopreservation and after thawing.</p><p><strong>Results: </strong>Density gradient processing reduced ROS production compared to washing (p < 0.05). No increase in the ROS production was observed after thawing. In the fresh condition, both density gradient and washed samples showed a lower proportion of oxidized cells compared to raw samples (p < 0.001). Acrosomal damage was significantly higher in washed samples compared to other groups in fresh samples (p < 0.001). Cryopreservation caused acrosomal damage only in raw samples (p < 0.001), with gradient samples maintaining greater acrosomal integrity after thawing. Plasma membrane instability was lower in the gradient of the fresh group compared to raw or washed samples (p < 0.001). Cryopreservation induced plasma membrane destabilization in processed samples but not in samples frozen with seminal plasma. After thawing, plasma membrane destabilization was lower in the gradient group compared to raw and washed samples (p < 0.05 and p < 0.001). Cells in the gradient group showed higher mitochondrial potential (p < 0.001), followed by washed samples compared to raw samples (p < 0.01). Mitochondrial membrane potential was significantly impaired in all three processes, with no differences among the groups after thawing.</p><p><strong>Conclusion: </strong>Cryopreservation significantly damages the acrosome and mitochondria of spermatozoa. In normozoospermic patients, the gradient method selected higher-quality spermatozoa compared to other processes, preserving functional advantages after thawing.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AndrologyPub Date : 2025-06-15DOI: 10.1111/andr.70082
Bo-Yu Xiang, Jie Wen, Yun-Hao Wang, Zhen-Rui Liu, Jin-Shun An, Jing-Xuan Peng, Ling-Xiao Chen, Jian Ding, Gui-Lin Wang, Quan Cheng, Dong-Jie Li
{"title":"Identification of potential drug targets for erectile dysfunction with single-cell RNA sequencing: A Mendelian randomization study.","authors":"Bo-Yu Xiang, Jie Wen, Yun-Hao Wang, Zhen-Rui Liu, Jin-Shun An, Jing-Xuan Peng, Ling-Xiao Chen, Jian Ding, Gui-Lin Wang, Quan Cheng, Dong-Jie Li","doi":"10.1111/andr.70082","DOIUrl":"https://doi.org/10.1111/andr.70082","url":null,"abstract":"<p><strong>Background: </strong>A subset of patients with erectile dysfunction (ED) responds poorly to current pharmacological treatments, largely due to the limited availability of well-defined therapeutic targets beyond phosphodiesterase 5 inhibitors (PDE5i).</p><p><strong>Methods: </strong>This study used Mendelian randomization (MR) to identify potential therapeutic targets for ED. Cis-expression quantitative trait loci (cis-eQTL) were sourced from the eQTLGen Consortium (31,684 individuals). ED summary statistics were derived from two cohorts (229,980 individuals: 6175 ED cases, 223,805 controls; 95,178 individuals: 1154 ED cases, 94,024 controls). Co-localization analysis assessed shared single nucleotide polymorphism (SNP) influencing ED risk and gene expression. Drug prediction and molecular docking were utilized to validate the therapeutic potential of the identified drug targets, while single-cell RNA sequencing (scRNA-seq, dataset GSE206528) identified relevant cell types.</p><p><strong>Results: </strong>Two drug targets demonstrated significance across both cohorts and were corroborated by co-localization analysis. Phenome-wide association studies (PheWAS) revealed no associations with other traits. Molecular docking analysis indicated strong binding affinities between the drugs and proteins. ScRNA-seq results showed the target genes are predominantly expressed in endothelial cells (ECs), Schwann Cells (SWCs) and smooth muscle cells (SMCs).</p><p><strong>Conclusion: </strong>This study highlights two promising ED targets, encouraging future research on ECs and SMCs to advance drug development and improve treatment outcomes.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AndrologyPub Date : 2025-06-08DOI: 10.1111/andr.70080
Wenxin Li, Shuzhi Sun, Ling Fu, Yu Pan, Lin Qian, Lei Yu, Hongqiang Wang, Yunchao Zhang, Hanshu Wang, Tao Jing
{"title":"New insights into the pathological mechanism of varicocoele and its association with abnormal vascular remodeling in varicocoele patients.","authors":"Wenxin Li, Shuzhi Sun, Ling Fu, Yu Pan, Lin Qian, Lei Yu, Hongqiang Wang, Yunchao Zhang, Hanshu Wang, Tao Jing","doi":"10.1111/andr.70080","DOIUrl":"https://doi.org/10.1111/andr.70080","url":null,"abstract":"<p><strong>Background: </strong>The pathological mechanism of venous reflux in varicocoele (VC) remains unclear. The theory of vascular remodeling may play an important role.</p><p><strong>Objective: </strong>This study aims to explore the potential pathological mechanism of VC and its association with abnormal vascular remodeling in VC patients.</p><p><strong>Materials and methods: </strong>We collected specimens of spermatic veins from VC patients who received microsurgical varicocelectomies at the Department of Andrology, the Affiliated Hospital of Qingdao University, from January 2020 to January 2024. The spermatic veins of VC patients were divided into three subgroups based on diameter (<1 mm, 1-3 mm, and >3 mm), with a control group consisting of spermatic veins from hydrocele patients. Differences in venous morphology and ultrastructure between these groups were examined using optical microscopy (OM) and transmission electron microscopy (TEM). The expression of alpha-smooth muscle actin (α-SMA) and osteopontin (OPN) was evaluated by immunohistochemical staining and Western blot analysis.</p><p><strong>Results and discussion: </strong>Substantial hyperplasia and disordered arrangement of smooth muscle cells (SMCs) in the spermatic veins of VC patients were observed. Thickness and clumpy aggregation of collagen fibers were also noted under OM, with a significantly higher proportion observed. An increase in dense bodies and mitochondrial vacuolization in the VC group were revealed by TEM. Immunohistochemical staining showed that both α-SMA and OPN were enriched in SMCs. Western blot analysis showed that the expression of OPN was significantly greater in the 1-3 mm and >3 mm subgroups compared with the control group (p < 0.05), while the expression of α-SMA did not show a significant decrease.</p><p><strong>Conclusions: </strong>The pathological changes in morphology and overexpression of OPN in SMCs indicates a possible spermatic vascular transition from the contractile to secretory phenotype. This abnormal vascular remodeling might be associated with the reflux in the spermatic veins of VC patients.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AndrologyPub Date : 2025-06-06DOI: 10.1111/andr.70079
Pengcheng Kong, Shanshan Liang, Jiaping Pan, Mingru Yin, Xiaoming Teng
{"title":"Sperm SCSA DNA fragmentation index does not influence the euploidy rate of viable blastocysts in advanced-age women.","authors":"Pengcheng Kong, Shanshan Liang, Jiaping Pan, Mingru Yin, Xiaoming Teng","doi":"10.1111/andr.70079","DOIUrl":"https://doi.org/10.1111/andr.70079","url":null,"abstract":"<p><strong>Background: </strong>Oocytes from older females have a diminished ability to repair sperm DNA damage compared with those from younger females. Previous research has indicated that there is no significant correlation between sperm DNA fragmentation index (DFI) and the blastocyst euploidy rate in cycles utilizing oocytes donated by young individuals. However, it is still unclear whether a high DFI impacts the euploidy rate of blastocysts derived from oocytes obtained from women of advanced reproductive age.</p><p><strong>Objective: </strong>The aim of this study was to investigate the potential association between sperm DFI and the euploidy rate of viable blastocysts in women of advanced age undergoing preimplantation genetic testing for aneuploidy (PGT-A).</p><p><strong>Materials and methods: </strong>A total of 667 blastocysts from 492 couples, all with maternal ages of 38 years or older, who underwent intracytoplasmic sperm injection (ICSI) combined with PGT-A were included in this study. The sperm DFI values were measured using the Sperm Chromatin Structure Assay (SCSA), and the couples were divided into three groups based on sperm DFI values: low DFI (DFI < 15%), moderate DFI (15% ≤ DFI ≤ 30%), and high DFI (DFI > 30%).</p><p><strong>Results: </strong>No statistically significant differences were found in the rates of normal fertilization among the low, moderate, and high DFI groups (73.3%, 75.8%, and 75.4%, respectively; p > 0.05). Similarly, the rates of high-quality embryos were comparable among the groups (47.2%, 45.5%, and 45.7%, respectively; p > 0.05). The blastocyst formation rates also exhibited no significant differences among the groups (49.9%, 48.0%, and 49.3%, respectively; p > 0.05). Additionally, the aneuploidy rates of viable blastocysts were comparable across the groups (55.1%, 59.1%, and 60.6%, respectively; p > 0.05). Both the categorical analysis based on clinical DFI thresholds (<15%, 15%-30%, >30%) and the multiple linear regression treating DFI as a continuous variable (adjusted for female age, female body mass index [BMI], duration of infertility, number of miscarriages, and male age) revealed no statistically significant association between DFI and blastocyst euploidy rates (p = 0.733 for the categorical analysis; B = -0.003, standard error [SE] = 0.002; p = 0.136 for the continuous model). Furthermore, clinical pregnancy outcomes and neonatal results following the transfer of euploid blastocysts were comparable among the groups.</p><p><strong>Discussion and conclusion: </strong>This study's findings suggest that elevated sperm DFI, as measured by the SCSA, does not significantly influence the euploidy rate of viable blastocysts in couples with advanced maternal age, whereas maternal age remains the predominant factor influencing embryo euploidy.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mapping the immune cells of the testis: Key insights into sexual maturation.","authors":"Xiaoyu Wu, Chenzhao Feng, Zunpan Fan, Yongfeng Wang, Huiping Zhang, Kai Zhao","doi":"10.1111/andr.70077","DOIUrl":"https://doi.org/10.1111/andr.70077","url":null,"abstract":"<p><strong>Background: </strong>The testicular immune microenvironment sustains homeostasis and immune privilege. However, the presence and functional significance of B cells within this specialized niche remain poorly characterized. Furthermore, the intricate crosstalk between resident immune populations and testicular stromal cells that may orchestrate the immunological and endocrine microenvironment during sexual maturation warrants systematic investigation.</p><p><strong>Objective: </strong>To systematically delineate the immune cell atlas and developmental trajectory of testicular leukocytes before and after sexual maturation.</p><p><strong>Materials and methods: </strong>An integrated analysis of leukocytes in post-sexual maturity (8-week-old) and pre-sexual maturity (2-week-old) mouse testes using single-cell RNA sequencing (scRNA-seq) and mass cytometry (CyTOF), was performed. Magnetic-activated cell sorting (MACS) isolated immune subsets, followed by bioinformatics interrogation of cellular heterogeneity and ligand-receptor network analysis to map intercellular communication pathways.</p><p><strong>Results: </strong>Through scRNA-seq clustering analysis, we resolved 18 distinct leukocyte populations (11 lymphoid and seven myeloid lineages), which were further validated and expanded to 17 phenotypically discrete subsets (eight lymphoid and nine myeloid) via high-dimensional CyTOF profiling. Notably, we identified a rare but functionally significant B lymphocyte population within the testicular compartment. The myeloid compartment exhibited pronounced developmental plasticity, marked by progressive Il1b<sup>+</sup>Macrophages diminution and regulatory T cell expansion during maturation. Cell communication network analysis revealed intensified ligand-receptor cross-talk between androgen-producing Leydig cells and CD8<sup>+</sup> T lymphocytes in post-pubertal testes, providing mechanistic insights into age-dependent immune privilege establishment.</p><p><strong>Discussion and conclusions: </strong>Multi-omics integration reveals dynamic immune remodeling during testicular maturation. These findings underscore the potential involvement of B cells in local immune surveillance while identifying maturation-associated signaling axes between stromal and immune cells. This comprehensive mapping of testicular leukocyte dynamics significantly advances our understanding of reproductive immunology and lays foundation for investigating immune-mediated testicular pathologies.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AndrologyPub Date : 2025-06-04DOI: 10.1111/andr.70068
Aileen Harrer, Esther G Meyron-Holtz, Andreas Meinhardt
{"title":"The role of iron in normal and impaired testicular function.","authors":"Aileen Harrer, Esther G Meyron-Holtz, Andreas Meinhardt","doi":"10.1111/andr.70068","DOIUrl":"https://doi.org/10.1111/andr.70068","url":null,"abstract":"<p><p>Iron plays a critical role in testicular physiology, impacting spermatogenesis, testosterone production, and overall testicular function. Iron homeostasis is maintained through systemic and cellular regulatory mechanisms, including hepcidin-mediated systemic iron control and the iron-responsive element/iron regulatory protein (IRE/IRP) system at the cellular level. Germ cells require iron for cell divisions and development, while Leydig and Sertoli cells depend on iron for the biosynthesis of testosterone and the maintenance of sperm development, with iron-dependent enzymes playing essential roles in lipid metabolism, DNA synthesis, and mitochondrial function. Iron imbalances, including iron overload and deficiency, significantly impact testicular health. Excess iron accumulation induces oxidative stress, lipid peroxidation, and ferroptosis, contributing to testicular dysfunction. Hereditary hemochromatosis and beta-thalassemia major are associated with disrupted iron metabolism, leading to altered hormonal profiles and impaired spermatogenesis. Conversely, iron deficiency, often linked to dietary insufficiency or inflammatory conditions, can impair testosterone production and sperm quality. Bacterial and viral infections of the testis, such as those caused by Escherichia coli, Zika virus, and HIV, also alter iron metabolism, influencing immune responses and exacerbating testicular inflammation. Additionally, chronic conditions such as obesity and diabetes may disrupt iron regulation and contribute to reproductive dysfunction. Emerging evidence suggests a strong link between ferroptosis and testicular damage, with iron-dependent lipid peroxidation playing a key role in cell death pathways. This review highlights the complexity of iron regulation in the testis, the negative effects of disruptions of iron metabolism on male fertility and reproductive health as well as the gaps in knowledge that currently prevent therapeutic approaches to mitigate infertility associated with iron dysregulation.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AndrologyPub Date : 2025-06-04DOI: 10.1111/andr.70067
Monica Levy Andersen, Allan Saj Porcacchia, Guilherme Luiz Fernandes, Tathiana A Alvarenga, Sergio Tufik
{"title":"Unraveling the intersection of sleep disorders and erectile dysfunction: Outcomes from two EPISONO editions.","authors":"Monica Levy Andersen, Allan Saj Porcacchia, Guilherme Luiz Fernandes, Tathiana A Alvarenga, Sergio Tufik","doi":"10.1111/andr.70067","DOIUrl":"https://doi.org/10.1111/andr.70067","url":null,"abstract":"<p><strong>Background: </strong>There is growing interest in the relationship between sleep disorders and erectile dysfunction. We present the results from a 2015 follow-up study in relation to the 2007 edition of Epidemiologic Sleep Study (EPISONO), a population-based sleep study conducted in São Paulo, Brazil, and from the 4th edition of EPISONO (2018), with respect to the incidence and prevalence of erectile dysfunction, and the associated risk factors. We hypothesized that the presence of erectile dysfunction would be associated with total testosterone levels and obstructive sleep apnea in both longitudinal and cross-sectional analyses.</p><p><strong>Method: </strong>The participants underwent polysomnography, and testosterone assays were performed. They also completed a range of health questionnaires. The sample comprised men aged 20‒80 years. In the longitudinal analysis, incidence the (N = 256) and prevalence (N = 300) of erectile dysfunction were calculated, and a generalized estimating equation model was constructed. For the analysis of the data from 2018, prevalence (N = 314), binomial logistic regression, and mediation-moderation models were calculated.</p><p><strong>Results: </strong>An overall incidence of 10.55% of erectile dysfunction was found in the follow-up, which was higher in men older than 50 years. In the longitudinal model, older age (odds ratio = 1.09), more depression symptoms (odds ratio = 1.05), and low total testosterone concentration (odds ratio = 2.69) were significant predictors of erectile dysfunction. Psychological well-being (World Health Organization Quality of Life) was a predictor of lowered odds of having erectile dysfunction (odds ratio = 0.87). In EPISONO 2018, a 20.06% general prevalence of erectile dysfunction was identified, and this prevalence was higher in age groups over 50 years. The odds of having erectile dysfunction were increased by age (odds ratio = 1.07), and the psychological domain of World Health Organization Quality of Life was associated with lowered odds of having erectile dysfunction (odds ratio = 0.65). Mediation models revealed a statistically significant mediation of apnea‒hypopnea index between the effect of age on total testosterone. The model that included age as the independent variable, apnea‒hypopnea index as a mediator and erectile dysfunction as the outcome resulted in significant effects of age but not apnea‒hypopnea index.</p><p><strong>Conclusions: </strong>This study highlights the importance of aging, psychological quality of life, testosterone concentration, and depressive symptoms in the context of erectile dysfunction. An association between obstructive sleep apnea and erectile dysfunction was observed, but it was not independent of age. The longitudinal results emphasize that, besides aging, these are modifiable factors that can be the subject of interventions to mitigate the development of erectile dysfunction over time.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AndrologyPub Date : 2025-06-03DOI: 10.1111/andr.70072
Shengrong Du, Shan Xu, Lei Yang, Yan Ye, Yuhan Wu, Ziyun Xiao, Xiuqing Dong, Wenliang Yao, Hua Li
{"title":"Cryptorchidism: Novel genetic insights into CCDC149 mutations.","authors":"Shengrong Du, Shan Xu, Lei Yang, Yan Ye, Yuhan Wu, Ziyun Xiao, Xiuqing Dong, Wenliang Yao, Hua Li","doi":"10.1111/andr.70072","DOIUrl":"https://doi.org/10.1111/andr.70072","url":null,"abstract":"<p><strong>Background: </strong>Cryptorchidism, characterized by the failure of one or both testes to descend into the scrotum, is a common congenital condition that can lead to infertility and increased risk of testicular cancer. CCDC149, a coiled-coil domain-containing protein, has been implicated in various developmental processes, but its role in the male reproductive system remains unexplored.</p><p><strong>Objective: </strong>This study aims to investigate the role of CCDC149 mutations in the development of bilateral cryptorchidism and to elucidate the underlying molecular mechanisms.</p><p><strong>Materials and methods: </strong>We conducted a whole-exome sequencing of an 8-year-old boy diagnosed with bilateral cryptorchidism, revealing a mutation in the CCDC149 gene. To further explore the functional implications of this mutation, we utilized CRISPR/Cas9 technology to generate Ccdc149 knockout mice. The phenotypic characteristics of these mice were assessed, focusing on testicular descent and sperm morphology. Additionally, single-cell RNA sequencing was performed to analyze the expression of genes associated with CCDC149, including anti-Müllerian hormone (AMH) and muscle-related factors.</p><p><strong>Results: </strong>The Ccdc149 knockout mice exhibited significant phenotypic traits consistent with cryptorchidism, including undescended testes and oligoasthenoteratozoospermia. Single-cell RNA sequencing analysis revealed altered expression patterns of AMH and several muscle-related genes, suggesting a potential regulatory interaction between CCDC149, AMH, and muscle development factors in the context of testicular descent.</p><p><strong>Discussion: </strong>Our findings provide novel genetic insights into the role of CCDC149 mutations in cryptorchidism. The observed phenotypic characteristics in the knockout mice, along with the gene expression analysis, indicate that CCDC149 may be crucial for normal testicular descent through its interaction with AMH and muscle-related factors. These results highlight the importance of further research into the molecular mechanisms underlying cryptorchidism, which could lead to improved diagnostic and therapeutic strategies for affected individuals.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparative efficacy of varicocelectomy and intrauterine insemination in varicocoele patients with mild semen abnormalities: An observational study.","authors":"Yanlin Ma, Weiming Deng, Tingting Wu, Qi Li, Yuanjie Li, Wenjie Mai, Lizheng Yan, Changwei Liang, Lingxiao Zhang","doi":"10.1111/andr.70070","DOIUrl":"https://doi.org/10.1111/andr.70070","url":null,"abstract":"<p><strong>Background: </strong>Varicocoele is a common cause of male infertility, affecting spermatogenesis through increased testicular temperature, venous stasis, and oxidative stress. Microsurgical subinguinal varicocelectomy improves semen quality, whereas intrauterine insemination is widely used for mild male factor infertility. The comparative efficacy of these treatments in varicocoele patients with mild semen abnormalities remains unclear.</p><p><strong>Objectives: </strong>To evaluate the efficacy of microsurgical subinguinal varicocelectomy and intrauterine insemination in improving clinical pregnancy and live birth rates in varicocoele patients with mild semen abnormalities and assess post-operative improvements in semen parameters following microsurgical subinguinal varicocelectomy.</p><p><strong>Materials and methods: </strong>A retrospective cohort study involving 650 microsurgical subinguinal varicocelectomy patients from five medical centers and 700 intrauterine insemination patients from one center was conducted. Inclusion criteria included varicocoele diagnosed via ultrasonography, mild semen abnormalities (total motile sperm count ≥5 million), and at least one abnormal semen parameter. Primary outcomes were clinical pregnancy and live birth rates. Secondary outcomes included sperm concentration, motility, and total motile sperm count changes post-microsurgical subinguinal varicocelectomy. Statistical analyses included chi-square tests and logistic regression.</p><p><strong>Results: </strong>Microsurgical subinguinal varicocelectomy patients demonstrated significant improvements in sperm concentration (35.2-43.3 × 10⁶/mL), motility (26%-38%), and total motile sperm count (18.8-34.9 × 10⁶, p < 0.001). Clinical pregnancy and live birth rates were higher in the microsurgical subinguinal varicocelectomy group (35.23% and 31.08%) compared to the intrauterine insemination group (29.57% and 24.00%, p < 0.05). Multivariate analysis revealed that microsurgical subinguinal varicocelectomy significantly increased pregnancy (OR = 1.43, 95% CI: 1.12-1.83, p < 0.05) and live birth rates (OR = 1.56, 95% CI: 1.21-2.02, p < 0.05).</p><p><strong>Discussion and conclusion: </strong>Microsurgical subinguinal varicocelectomy significantly enhances semen quality and achieves superior clinical pregnancy and live birth rates compared to intrauterine insemination for varicocoele patients with mild semen abnormalities. These findings suggest that microsurgical subinguinal varicocelectomy is a more effective treatment option, highlighting the importance of individualized treatment strategies and supporting the preferential use of surgical intervention in this specific patient population.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}