Andrology最新文献

{"title":"Busulfan-Induced Male Infertility: Mechanisms, Therapeutic Interventions, and Future Directions","authors":"Tianyu Li,&nbsp;Zhichen Tang,&nbsp;Yaping Song,&nbsp;Xiaolei Luo,&nbsp;Bin Zhou,&nbsp;Xiao Liu,&nbsp;Fuping Li,&nbsp;Yanyun Wang,&nbsp;Lin Zhang","doi":"10.1111/andr.70189","DOIUrl":"10.1111/andr.70189","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>This review summarizes the molecular and cellular mechanisms underlying busulfan-induced male infertility and evaluates the translational potential of current and emerging therapeutic strategies. Evidence indicates that busulfan induces germ cell DNA alkylation damage, triggers sustained oxidative stress, and activates multiple cell death pathways. These events are accompanied by supporting cell dysfunction, disruption of the blood–testis barrier (BTB), and endocrine imbalance, collectively driving progressive impairment of spermatogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <p>In response to these pathological processes, various interventions have been explored, including antioxidant molecules, natural extracts, epigenetic modulation, and stem cell–related approaches, many of which show partial improvement of spermatogenic function in experimental models. In addition, clinical strategies used for other forms of male infertility, such as gonadotropin supplementation and antioxidant supportive therapy, provide relevant reference frameworks for chemotherapy-associated fertility impairment. However, most studies on busulfan-induced infertility remain preclinical, and their benefits largely reflect supportive modulation of the testicular microenvironment rather than definitive restoration of spermatogonial stem cells (SSCs) or repair of genotoxic damage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <p>Based on an integrated assessment of current evidence, this review highlights key unresolved challenges, including the lack of a defined therapeutic safety window, limitations in targeted delivery, and difficulties in achieving fundamental reconstruction of the spermatogenic system. Accordingly, future studies should place greater emphasis on more effective isolation and protection of testicular tissue, development of targeted drug delivery systems, and strategies aimed at spermatogenic system reconstruction.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"14 7","pages":"1929-1940"},"PeriodicalIF":3.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/andr.70189","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Muscle Strength and Power Changes With Gender-Affirming Hormone Therapy","authors":"Mathilde Kamp Nørlund,&nbsp;Jakob Lindberg Nielsen,&nbsp;Marianne Skovsager Andersen,&nbsp;Rikke Hjortebjerg,&nbsp;Laust Frisenberg Buhl,&nbsp;Anne Pernille Hermann,&nbsp;Camilla Viola Buskbjerg Palm,&nbsp;Tine Taulbjerg Kristensen,&nbsp;Jan Frystyk,&nbsp;Per Aagaard,&nbsp;Jonas Mathiesen,&nbsp;Dorte Glintborg,&nbsp;Louise Lehmann Christensen","doi":"10.1111/andr.70132","DOIUrl":"10.1111/andr.70132","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To assess prospective changes in maximal muscle strength and muscle power from before and after 1 year of GAHT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design and Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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 (<i>p</i> ≤ 0.001) and 5.0 kg (7%) in TransM_ongoing (<i>p</i> ≤ 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.</p>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Upper body muscle strength but not power increased during masculinizing GAHT, whereas muscle strength and power decreased within the first year of feminizing GAHT.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"14 7","pages":"2138-2149"},"PeriodicalIF":3.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/andr.70132","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Live Birth Rates After Varicocele Embolization in Patients After Failed In Vitro Fertilization With Intracytoplasmic Sperm Injection","authors":"Anthony Verstandig,&nbsp;Adam Farkas","doi":"10.1111/andr.70328","DOIUrl":"10.1111/andr.70328","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objectives</h3>\u0000 \u0000 <p>While in vitro fertilization with intracytoplasmic sperm injection (IVF-ICSI) bypasses abnormalities in sperm concentration, motility, and morphology, it still has a significant failure rate. We report our experience on the effect of varicocele embolization (VE) on couples with varicocele related primary male factor infertility in whom IVF/ICSI failed to result in a live birth (LB).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and Methods</h3>\u0000 \u0000 <p>This single center retrospective cohort study documents 42 couples who had failed to have a LB after single or multiple IVF/ICSI cycles and in whom the male partner subsequently had left or bilateral varicoceles treated by transcatheter embolization. Other inclusion criteria were maternal age of 35 or less at the time of VE and at least 24 months follow up after embolization. The end point was LB by natural conception or by IVF-ICSI.</p>\u0000 \u0000 <p>Pre-procedure data was documented at the time of referral for varicocele embolization. Images of the procedures were reviewed, and post VE data was collected by telephone questionnaire from one of the partners.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Prior to varicocele embolization, the 42 couples had undergone 151 oocyte retrievals (median 2, range 1–21) and 200 embryo transfers (median 3, range 1–26) with no LB.</p>\u0000 \u0000 <p>During a median follow up period of 54 months (range 25–111) following VE, there were 60 LB (65 children) amongst 36 of the 42 couples (86%). Thirty-four couples underwent a total of 119 oocyte retrievals and 149 embryo transfer procedures with 28 achieving 36 LB (41 children). Fifteen couples had 23 LB (23 children) from natural conceptions. One couple had an LB after intrauterine insemination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>VE in this challenging patient population may treat varicocele associated sperm function problems not addressed by ICSI and could be beneficial before assisted reproductive techniques in varicocele related male factor infertility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"14 7","pages":"2081-2086"},"PeriodicalIF":3.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/andr.70328","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromodomain Helicase DNA–Binding Proteins and Spermatogenesis: Current Advances","authors":"Mingrui Zhang,&nbsp;Di Liu,&nbsp;Guoqiang Liu,&nbsp;Minggang Zhu,&nbsp;Feng Pan","doi":"10.1111/andr.70232","DOIUrl":"10.1111/andr.70232","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Male infertility is a prevalent clinical condition, with approximately one-third of cases classified as idiopathic, frequently stemming from impaired spermatogenesis because of dysregulated gene expression. Chromodomain helicase DNA-binding (CHD) proteins are central chromatin remodelers that orchestrate this epigenetic regulation. For instance, smoking-induced hypermethylation of the <i>CHD5</i> gene promoter is associated with impaired semen parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This review aims to summarize the roles and mechanisms of CHD proteins in spermatogenesis, explore their relationship with male infertility, and discuss their potential as diagnostic and therapeutic targets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A comprehensive literature review was conducted to synthesize current findings on the expression and function of CHD proteins across different stages of spermatogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Research has shown that CHD proteins are expressed in the testis and play crucial roles in multiple stages of spermatogenesis, from spermatogonial stem cell (SSC) maintenance to spermatid maturation, making them promising targets for understanding and treating male infertility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CHD proteins represent important epigenetic regulators in spermatogenesis and may serve as valuable biomarkers or therapeutic targets for male infertility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"14 7","pages":"1962-1970"},"PeriodicalIF":3.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/andr.70232","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Metabolism Governs Spermatogonial Stem Cell Fate Decisions","authors":"Zhimin Ma,&nbsp;Qi Geng,&nbsp;Huaibing Zhu,&nbsp;Dingfeng Zou,&nbsp;Dingyao Chen,&nbsp;Kai Li,&nbsp;Wei Song","doi":"10.1111/andr.70241","DOIUrl":"10.1111/andr.70241","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Spermatogonial stem cells (SSCs) sustain lifelong spermatogenesis through their unique capacity for self-renewal and differentiation. While transcriptomic regulation has long been emphasized, recent advances in multi-omics have highlighted mitochondrial metabolism as a pivotal regulator of SSC fate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This review aims to summarize current advances in how mitochondrial metabolism regulates SSC fate decisions and to explore its pathological alterations and potential therapeutic targets in obesity-associated male infertility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This review delves deeper into the core mechanisms by which mitochondria govern SSC fate decisions, integrating findings from multi-omics, metabolic assays, and animal models. We also provide a comprehensive overview of published literature on mitochondrial dysfunction in obesity-related infertility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and Conclusion</h3>\u0000 \u0000 <p>Quiescent SSCs predominantly rely on glycolysis within a hypoxic niche, whereas differentiation is accompanied by a metabolic shift toward oxidative phosphorylation (OXPHOS), alongside mitochondrial maturation and remodeling. Beyond energy production, mitochondria function as critical signaling hubs that integrate redox regulation, mitochondrial dynamics, and metabolite-dependent epigenetic mechanisms to dictate SSC fate. Conversely, in the context of obesity, mitochondrial dysfunction, characterized by excessive reactive oxygen species (ROS) production, mitochondrial fragmentation, and impaired quality control, severely disrupts SSC homeostasis and drives male infertility.</p>\u0000 \u0000 <p>Maintaining mitochondrial metabolic integrity is essential for normal SSC function. Targeting mitochondrial quality control and restoring metabolic balance represent promising emerging therapeutic strategies for the treatment of obesity-related male infertility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"14 7","pages":"2018-2031"},"PeriodicalIF":3.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/andr.70241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence in Semen Analysis and Sperm Selection: Opportunities and Challenges.","authors":"Federica Quaranta, Nicole Dalia Cilia, Gaia Cicolani, Vittorio Di Pietro, Enrico Delli Paoli, Silvia Di Chiano, Francesco Lombardo, Donatella Paoli, Francesco Pallotti","doi":"10.1111/andr.70389","DOIUrl":"https://doi.org/10.1111/andr.70389","url":null,"abstract":"<p><strong>Background: </strong>Male factors contribute to approximately half of all cases of couple infertility, and semen analysis remains the cornerstone of the diagnostic evaluation. In recent years, artificial intelligence (AI) has emerged as a promising tool to improve the objectivity and reproducibility of semen analysis and sperm selection in assisted reproductive technologies (ART).</p><p><strong>Materials and methods: </strong>This narrative review provides an overview of the current applications of AI in seminology, focusing on sperm motility, morphology, DNA fragmentation, sperm selection for intracytoplasmic sperm injection (ICSI), and sperm retrieval in men with nonobstructive azoospermia. Beyond laboratory applications, the review also highlights the emerging role of machine learning in predicting reproductive outcomes and supporting clinical decision-making in andrology.</p><p><strong>Results and discussion: </strong>Although the available evidence is encouraging, most studies remain limited by small and highly selected datasets, a lack of external validation, and scarce evidence on clinically meaningful outcomes. Future progress in the field will likely depend not only on improvements in algorithm performance, but also on the availability of high-quality, representative datasets to enable robust validation and reliable clinical translation. While issues related to data quality, algorithmic bias, and regulatory and ethical aspects still need to be addressed, AI has the potential to become a valuable decision-support tool in reproductive medicine.</p><p><strong>Conclusions: </strong>Nonetheless, further prospective multicenter studies are needed before these technologies can be routinely integrated into clinical practice.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015438","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":"The severity classification of lifelong premature ejaculation based on the premature ejaculation diagnostic tool","authors":"Qianghui Zhong,&nbsp;Chunlin Wang,&nbsp;Dake Zhu,&nbsp;Karl H. Pang,&nbsp;Elena Colonnello,&nbsp;Andrea Sansone,&nbsp;Qingshan Chen,&nbsp;Emmanuele A. Jannini,&nbsp;Yan Zhang","doi":"10.1111/andr.70124","DOIUrl":"10.1111/andr.70124","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Grading premature ejaculation (PE) may hold significant value. However, although previous studies have attempted to achieve a uniform severity scale for PE, this has not been widely accepted since design and methodological limitations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>In patients with lifelong PE (LPE), we re-evaluated the items suitable for severity grading and established the appropriate severity classification reference through reasonable statistical methods and logic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and methods</h3>\u0000 \u0000 <p>Patient perceived intravaginal ejaculatory latency time (PIELT) and premature ejaculation diagnostic tool (PEDT) scores from 264 men (149 with LPE and 115 without PE) were used to analyze surrogate item suitable for classification. Classification and Regression Trees were used to determine the optimal score interval for different severity levels in patients with LPE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>For the LPE population with PIELT &lt; 3.5 min, PIELT had no value in the classification of severity of LPE patients. PEDT items 1 and 4, showing high correlation (0.84 and 0.89, respectively) with PEDT total score, reflect the physical and mental effects of LPE patients in terms of ejaculatory control and interpersonal relationship. These items may serve as proxy for the severity scale of LPE patients. Hence, patients diagnosed with LPE can be classified into the following grades based on PEDT scores: mild (11–14), moderate (15–17), severe (18–20). Substantial agreement was shown between these predicted and “true” classes (weighted kappa 0.71).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Assessing LPE according to three dimensions is a widely accepted definition. While PIELT showed no statistically significant differences in the classification (<i>p</i> &gt; 0.05), the two subjective dimensions of ejaculation control and negative psychological influence did predict the severity grading of LPE. Not only can grading the subjective feelings of patients with LPE help them to self-assess the extent of the disease, but also provide a valuable reference for further treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Within the PIELT of 3.5 min, the severity of LPE can be classified into severe, moderate, and mild categories based on the PEDT score.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"14 7","pages":"2118-2125"},"PeriodicalIF":3.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136231","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":"Metabolic Reprogramming in Male Infertility: Mechanistic Integration and Translational Perspectives From Mouse Models","authors":"Jinyue Rong,&nbsp;Lina Wang,&nbsp;Huiming Yan,&nbsp;Jichun Tan,&nbsp;Meng Dong","doi":"10.1111/andr.70276","DOIUrl":"10.1111/andr.70276","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Spermatogenesis is a highly energy-dependent and tightly regulated differentiation process in the male reproductive system, characterized by dynamic, stage-specific metabolic adaptations during spermatogonial proliferation, meiosis and sperm maturation. Accumulating evidence suggests that successful spermatogenesis is associated with a coordinated program of metabolic reprogramming, which involves the sequential and context-dependent utilization of distinct bioenergetic pathways rather than dependence on a single energy source. Importantly, metabolic reprogramming represents a physiological and tightly controlled process, whereas metabolic dysfunction arises from its disruption or dysregulation. Studies using mouse models, supported by single-cell omics and metabolic analyses, indicate stage-associated transitions from glycolysis to oxidative phosphorylation (OXPHOS), followed by increased utilization of alternative substrates such as fatty acids and amino acids during germ cell development. These transitions are orchestrated by interconnected networks involving energy-sensing pathways, endocrine regulation and metabolite-driven epigenetic modifications. Disruption of this finely tuned metabolic reprogramming leads to metabolic dysfunction, characterized by oxidative stress, mitochondrial impairment, meiotic defects and chromatin instability, ultimately compromising spermatogenic homeostasis and contributing to idiopathic male infertility. Consistent evidence from experimental and clinical studies further suggests that systemic metabolic disorders, including obesity, diabetes, and dyslipidaemia, as well as exposure to endocrine-disrupting chemicals, may impair metabolic coupling between Sertoli cells and germ cells, thereby exacerbating testicular metabolic imbalance. These disturbances exacerbate mitochondrial dysfunction, one-carbon metabolic imbalance, and blood–testis barrier (BTB) disruption, ultimately leading to reduced sperm quality and fertility. Building on these insights, we propose a metabolism-centred classification framework that stratifies idiopathic male infertility into glycolysis-impaired, OXPHOS-deficient, lipid-overload, and one-carbon metabolism–dysregulated subtypes. We further discuss the translational potential of targeting metabolic pathways through mitochondrial-directed antioxidants, modulation of energy-sensing signalling, and nutritional interventions. Finally, we highlight the need for future studies integrating in vivo metabolic imaging, testicular organoid models and non-invasive seminal metabolomic biomarkers, alongside well-designed clinical trials, to advance metabolism-based precision diagnostics and therapeutics for male infertility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"14 7","pages":"2032-2056"},"PeriodicalIF":3.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/andr.70276","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148238594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reinke Crystals are Immunoreactive for Purine-Synthesising Metabolic Enzymes","authors":"John Woulfe,&nbsp;Trevor A. Flood,&nbsp;Sharlene Faulkes,&nbsp;David G. Munoz","doi":"10.1111/andr.70302","DOIUrl":"10.1111/andr.70302","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Reinke crystals are a defining histological feature of human adult Leydig cells, the testosterone-producing cells of the testis. These structures are present in the cytoplasm and the nucleus and display quantitative alterations in a variety of physiological and pathological contexts. The functional significance and protein composition of Reinke crystals have remained elusive for over a century.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>We sought to explore the protein composition of Reinke crystals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Double labelling immunofluorescence for the purine nucleotide-synthesizing enzymes inosine monophosphate dehydrogenase (IMPDH) and phosphoribosyl pyrophosphate synthetase (PRPS) and confocal microscopic imaging were performed on samples of human Leydig cell tumours and adjacent non-neoplastic testis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We demonstrate that Reinke crystals are intensely immunoreactive for IMPDH and PRPS, two key rate-limiting enzymes in the de novo synthesis of purine nucleotides.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>IMPDH and PRPS are two of several metabolic enzymes that are capable of forming mesoscale filamentous aggregates as a mechanism to regulate enzyme activity. IMPDH is also able to form crystals in cellulo. Our observations potentially link Reinke crystal formation to purine nucleotide metabolism in Leydig cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>If confirmed in future studies, this finding may have important implications for understanding metabolic contributions to male reproductive disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"14 7","pages":"2063-2070"},"PeriodicalIF":3.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148389884","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":"6-Nitrodopamine as a Novel Mediator of Prostatic Smooth Muscle Function in Mouse and Human.","authors":"Alline Araujo Curiel, Fabio Henrique da Silva, Jéssica Mariana Dias, Luise Gabriela Santos Pereira, Douglas Rafael Martins Dias, Amanda Bueno Olivotti, André Almeida Schenka, Valéria Barbosa de Souza, Masato Tsutsui, Fabiola Zakia Monica, Edson Antunes, Gilberto De Nucci, Mariana G de Oliveira","doi":"10.1111/andr.70391","DOIUrl":"https://doi.org/10.1111/andr.70391","url":null,"abstract":"<p><strong>Background: </strong>Epithelium-derived catecholamines contribute to local regulation of genitourinary smooth muscle function, but the role of the endogenous 6-nitrodopamine (6-ND) in the prostate remains unknown.</p><p><strong>Objectives: </strong>To determine whether 6-ND is produced by mouse and human prostate and its role in smooth muscle regulation.</p><p><strong>Methods: </strong>Catecholamine release was quantified by LC-MS/MS. Tyrosine hydroxylase (TH) expression was assessed by immunohistochemistry and FISH. Functional responses were evaluated by myography and void spot assay.</p><p><strong>Results: </strong>Basal 6-ND release was detected in mouse and human prostate. In mice, release was partially sensitive to tetrodotoxin (TTX), whereas in human tissues it was largely TTX-resistant. TH expression was identified in the prostatic epithelium. Functionally, 6-ND relaxed pre-contracted tissues, attenuated neurogenic contractions, and reduced noradrenaline potency. Genetic deletion of nitric oxide synthases (e/i/nNOS^-/-) or inhibition was associated with prostatic hypercontractility and reduced voiding frequency. Although 6-ND-induced relaxation was independent of the NO-sGC-cGMP pathway and did not increase intracellular cAMP, it potentiated forskolin-induced relaxation.</p><p><strong>Discussion: </strong>These findings identify 6-ND as an endogenous modulator of prostatic smooth muscle function and are consistent with a dual regulatory system integrating neuronal and epithelial catecholamine sources.</p><p><strong>Conclusion: </strong>6-ND represents a novel pathway involved in local prostate regulation and a potential therapeutic target for prostatic disorders.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975456","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}