Andrology最新文献

{"title":"Abstract.","authors":"","doi":"10.1111/andr.70012","DOIUrl":"https://doi.org/10.1111/andr.70012","url":null,"abstract":"","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647004","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":"Prevalence and impact of antisperm antibodies on semen quality and male reproductive health aspects: A 10-years retrospective study.","authors":"Andreia Filipa Neves Silva, Maria Schubert, Sabine Kliesch, Stefan Schlatt, Joao Ramalho-Santos, Sandra Catarina Gomes Amaral","doi":"10.1111/andr.70020","DOIUrl":"https://doi.org/10.1111/andr.70020","url":null,"abstract":"<p><strong>Background: </strong>The association between antisperm antibodies (ASA) and male (in)fertility is not fully understood, mainly due to contradictory reports. However, there is indication that ASA might affect several male reproductive health aspects warranting further investigation.</p><p><strong>Objective: </strong>To investigate the prevalence and impact of ASA on semen quality and its association with male reproductive function.</p><p><strong>Materials and methods: </strong>ASA presence was evaluated by the MAR test. Their prevalence, impact on semen quality and several aspects of male reproductive function were assessed, retrospectively, in a cohort of 2727 men, divided in 4 groups according to the percentage of ASA (without ASA, 10%-49% ASA, ≥50% ASA, and 10%-100% ASA).</p><p><strong>Results: </strong>The prevalence of ASA was 1.4%. When compared to the group without ASA, patients with ≥50% ASA, presented a higher percentage of semen agglutinates and leukocytes, and higher testicular volume. Subjects with 10%-49% and 10%-100% ASA, had lower levels of FSH and fructose, and higher levels of estradiol, α-glucosidase, and higher testicular volume. Furthermore, the 10%-49% ASA group presented a higher agglutination and percentage of round cells and leukocytes, when compared with the group without ASA. Similar results were observed in the 10%-100% ASA group. Interestingly, smoking habits were more frequent in the ≥50% ASA group, compared with the 10%-49% ASA group, with the chance of having ASA at a pathological level being 2-fold higher.</p><p><strong>Discussion and conclusion: </strong>In this study, data on ASA prevalence, impact in semen quality and on several aspects of male reproductive health were analyzed in one of the biggest and thoroughly characterized cohorts so far. Agglutination and impaired motility remain the most revealing parameters of ASA presence and should be considered in the clinical ASA management. Interestingly, we are the first to report an association between smoking and pathological ASA levels. The reported higher testicular volume and lower FSH in ASA patients may be of clinical relevance, suggesting that ASA might also have a role in the impaired fertility, highlighting the importance of ASA testing especially in men with lacking etiologic factors.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596096","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":"Folding, misfolding, and regulation of intracellular traffic of G protein-coupled receptors involved in the hypothalamic-pituitary-gonadal axis.","authors":"Alfredo Ulloa-Aguirre, Ross C Anderson, Teresa Zariñán, Rubén Gutiérrez-Sagal, Eduardo Jardón-Valadez, Claire L Newton","doi":"10.1111/andr.70018","DOIUrl":"https://doi.org/10.1111/andr.70018","url":null,"abstract":"<p><strong>Background: </strong>G protein-coupled receptors are a large and functionally diverse family of membrane receptors involved in a number of biological processes. Like other proteins, G protein-coupled receptors need to be properly folded in order to traffic to the plasma membrane and interact with agonist.</p><p><strong>Objective: </strong>Herein, we briefly review the process of folding and intracellular traffic of G protein-coupled receptors, with a focus on the gonadotropin-releasing hormone receptor and the gonadotropin receptors, whose variants can lead to misfolding, loss of plasma membrane trafficking and eventually to different forms of hypogonadism.</p><p><strong>Results and discussion: </strong>Pathogenic variants of G protein-coupled receptors may provoke loss-of-function of the receptor protein, thereby leading to disease. The presence of a stringent cellular quality control system promotes proper protein folding compatible with endoplasmic reticulum export and concomitantly prevents unfolded proteins accumulating within the cell. Molecular chaperones and companion factors are key elements of the quality control system that maintain the integrity of the proteostasis network by regulating, at different levels folding and assembly of nascent proteins and by promoting degradation of defective conformers, preventing aggregation and toxic accumulation. Due to the importance of the concept of molecular chaperoning in protein folding, pharmacoperone drugs emulating the role of endogenous chaperones as stabilizers of protein conformation currently represent a novel therapeutic opportunity for rescuing misfolded receptors and treating different diseases due to protein misfolding.</p><p><strong>Conclusions: </strong>In vitro and in vivo studies in experimental animals and in humans have provided proof-of-principle of the beneficial effects of pharmacoperone drugs in modifying the course of human disease due to misfolding of G protein-coupled receptors.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571512","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":"Fructose as a key biomarker for prognostication in idiopathic obstructive azoospermia associated with CFTR and ADGRG2 gene variants.","authors":"Zhongkun Liang, Tuerxunayi Yalikun, Xiaohui Ji, Jin Li, Ling Zhou, Jing Zhang, Jing Tian, Hui Chen, Ping Yuan","doi":"10.1111/andr.70014","DOIUrl":"https://doi.org/10.1111/andr.70014","url":null,"abstract":"<p><strong>Background: </strong>Isolated obstructive azoospermia (iOA) is classified as a type of obstructive azoospermia (OA) where cases remain \"unexplained\" even after excluding congenital absence of the vas deferens and external factors. This study aimed to determine if certain semen characteristics in iOA patients could indicate underlying genetic variants.</p><p><strong>Objectives: </strong>To investigate CFTR and ADGRG2 gene variants in patients with idiopathic obstructive azoospermia (iOA) and identify semen parameters associated with these variants to guide genetic testing.</p><p><strong>Materials and methods: </strong>Seventy-six iOA patients were divided into three groups based on variant status: Group I, patients with at least two CFTR variants or a hemizygous ADGRG2 variant; Group II, patients with one CFTR variant and no ADGRG2 variants; Group III, patients without any CFTR or ADGRG2 variants. Associations between genotypes and clinical parameters were analyzed using univariate and multivariate logistic regression to identify potential biomarkers.</p><p><strong>Result(s): </strong>Thirty-six of the 76 patients (47.37%) carried one or more CFTR or ADGRG2 variants. Twenty distinct variants, including three novel variants (c.1851A > T and c.2426C > T in CFTR, c.1105G > A in ADGRG2), were identified. The most common variant was c.1210-12T[5] (5T) (18.42%), followed by c.1666A > G (4.61%) and c.4056G > C (3.95%). Group I patients had significantly lower ejaculate volume, pH, and fructose levels compared with Groups II and III. The combined area under the curve (AUC) for fructose, age, pH, and volume was 0.979, with fructose alone achieving an AUC of 0.952. Diagnostic efficacy for variant detection was highest (88.1%) at a fructose cutoff of 0.591 µmol/ejaculate, with a sensitivity of 0.958, a specificity of 0.923, a positive predictive value (PPV) of 0.895 and a negative predictive value (NPV) of 0.877.</p><p><strong>Discussion and conclusion: </strong>Approximately 47% of iOA patients carry CFTR and ADGRG2 variants, characterized by significantly lower semen volume, fructose, and pH. Fructose was identified as an independent predictor of CFTR and ADGRG2 variants, highlighting its potential utility in guiding genetic testing and clinical decision-making in iOA patients.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571513","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":"Initial motility and vitality predict the semen quality after long-term cryostorage, even in patients with restricted ejaculate parameters.","authors":"Simone Bier, Daniela Hanke, Michael Zitzmann, Sabine Kliesch, Verena Nordhoff","doi":"10.1111/andr.70019","DOIUrl":"https://doi.org/10.1111/andr.70019","url":null,"abstract":"<p><strong>Background: </strong>Cryopreservation of human semen is the cornerstone for preserving male fertility before gonadotoxic therapy or in cases of high variability in semen parameters. This is particular crucial in cases of severe oligoasthenoteratozoospermia (OAT), where diminished sperm counts may compromise planned intracytoplasmic sperm injection (ICSI) procedures. Previous investigations in donor programs have shown long-term storage effects, such as decreased motility in cryopreserved semen samples. However, these studies were based on patients exhibiting normozoospermic semen samples. To date, there has been no comprehensive evaluation of the effect of long-term cryostorage on sperm samples from individuals with compromised semen parameters.</p><p><strong>Objectives: </strong>The aim of this study was to identify the effect of long-term cryostorage on semen parameters such as motility and vitality. Additionally, we sought to identify variables, which could aid in predicting motility and vitality following the freeze-thaw process.</p><p><strong>Patients and methods: </strong>Within our center, we have archived sperm samples from 6022 patients cryopreserved between 2001 and 2019. Among these, 293 patients donated their samples for subsequent research following depot termination. We examined semen concentration, motility, morphology, and vitality of spermatozoa thawed after varying storage durations, alongside baseline metrics documented at the time of cryopreservation. Samples were stratified into three cohorts based on storage duration: 2.5 to ≤5 years, > 5 to ≤14 years, and > 14 years.</p><p><strong>Results: </strong>Our analysis revealed no changes in motility (p = 0.44), vitality (p = 0.08), or morphology (p = 0.44) across the cohorts. Regression analysis demonstrated that initial motility and sperm concentration were significantly associated with post-cryostorage motility, whereas storage duration was not (p = 0.72). Similarly, there was no association between storage duration and post-thaw value 2 vitality (p = 0.64).</p><p><strong>Discussion: </strong>The initial semen analysis as well as the evaluation of a short-term frozen sample immediately after cryopreservation, appeared to be the most important markers for predicting post-thaw motility and vitality.</p><p><strong>Conclusion: </strong>Our results demonstrate the reliability of long-term cryostorage of human spermatozoa for fertility preservation, even in individuals with constrained semen quality at the time of cryopreservation.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565832","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":"Dupless: Toward a patient-friendly approach for erectile dysfunction nature differentiation - a study of 291 penile duplex Doppler ultrasound assessments.","authors":"Hille J Torenvlied, Kim E de Jager, Loes I Segerink, Rob C M Pelger, Jack J H Beck","doi":"10.1111/andr.70017","DOIUrl":"https://doi.org/10.1111/andr.70017","url":null,"abstract":"<p><strong>Background: </strong>Erectile dysfunction (ED) is a condition commonly classified as either psychogenic or organic. Traditional age-based categorizations are considered overly simplistic, yet many clinicians continue to rely on initial evaluation-patient symptoms and history, physical examination, blood tests, and questionnaires-for diagnosis due to limited modern tools.</p><p><strong>Objectives: </strong>This study aims to evaluate the predictive value of patient characteristics in individuals with \"ED of indeterminate origin\" following initial evaluation. Identifying these variables could enhance early diagnosis and reduce reliance on invasive procedures.</p><p><strong>Materials and methods: </strong>A retrospective cohort study was conducted on patients who underwent penile duplex Doppler ultrasound between January 2018 and January 2024 due to \"ED of indeterminate origin\". Patient data, including demographics, lifestyle factors, and medical history, were collected and analyzed using unpaired t-tests, chi-squared tests, Fisher's exact tests, and multivariate logistic regression to assess their predictive value.</p><p><strong>Results: </strong>Among the 291 patients in the cohort, 165 (56.7%) were diagnosed with organic ED and 113 (38.8%) with psychogenic ED. Significant differences in age, history of diabetes mellitus, and drug use were noted. Logistic regression revealed multicollinearity among the variables and explained only 5.8% of the variance in ED etiology. Subgroup analysis revealed that diabetes mellitus predicts organic ED in patients aged 40 years and older, while psychopathology is linked to psychogenic ED. No significant predictors were identified for patients under 40 years.</p><p><strong>Discussion and conclusion: </strong>The findings of this \"Dupless\" study highlight the limitations of relying solely on initial evaluation to differentiate ED etiology, stressing the need for additional diagnostic tools. While some predictive factors were identified, they proved insufficient for clinical use. Thus, an urgent need exists for the development of modern, noninvasive diagnostic tools to enhance ED classification. Future research could explore machine learning models to uncover complex patterns not evident in traditional statistical methods.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522500","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":"Unveiling SMAD family member 6 as a novel biomarker for prognosis and immunotherapy response in testicular germ cell tumors.","authors":"Huawei Lin, Xiaowen Lin, Peisheng Huang, Xiaoxue Yu, Jianming Liu, Liangliang Huang, Yanni Wei, Jiahong Chen, Zhouda Cai, Le Zhang, Junhong Deng, Zhuoyuan Lin, Yu Zheng, Jianming Lu","doi":"10.1111/andr.70015","DOIUrl":"https://doi.org/10.1111/andr.70015","url":null,"abstract":"<p><strong>Background and objectives: </strong>Despite its rarity, testicular germ cell tumor (TGCT) is commonly diagnosed in young males aged 20-40. In recent years, the global prevalence of TGCT has gradually increased, with 12-30% of patients experiencing relapse and metastasis. However, there are currently no reliable biomarkers for accurately predicting the prognosis of TGCT patients. Therefore, identifying novel biomarkers for risk stratification in TGCT is an immediate priority.</p><p><strong>Materials and methods: </strong>Using TGCT samples from multiple centers, we identified a novel prognostic biomarker (SMAD family member 6 [SMAD6]) through differential expression analysis, Cox regression, and survival analysis. Immunohistochemistry (IHC) was then employed to evaluate SMAD6 expression levels in normal testicular tissues and TGCT samples. Finally, we examined the relationship between SMAD6 and its biological characteristics, mutation landscape, immune cell infiltration, and response to immunotherapy.</p><p><strong>Results: </strong>Our study identified SMAD6 as a risk factor for TGCT prognosis. IHC revealed significant expression of SMAD6 in TGCT tissues. Functional enrichment analysis indicated that SMAD6 may contribute to the activation of tumor progression-related pathways and suppression of immune-related pathways. Additionally, high SMAD6 expression was correlated with reduced CD8⁺ T cell infiltration, while patients with low SMAD6 expression benefited more from immunotherapy.</p><p><strong>Discussion and conclusions: </strong>This study highlights the potential of SMAD6 may be useful for TGCT prognosis and immunotherapy response prediction, offering a promising target for personalized medicine strategies.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490520","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":"Opioid-induced androgen deficiency in men: Prevalence, pathophysiology, and efficacy of testosterone therapy.","authors":"Hussein Kafel, Milena Braga-Basaria, Shehzad Basaria","doi":"10.1111/andr.70013","DOIUrl":"https://doi.org/10.1111/andr.70013","url":null,"abstract":"<p><strong>Background: </strong>Opioid analgesics are frequently prescribed for the treatment of chronic pain and are a common cause of male androgen deficiency. Despite its high prevalence, this adverse effect of chronic opioid use remains underappreciated by clinicians. As a result, androgen deficiency remains underdiagnosed and likely undertreated. This focused review discusses the expanding literature on opioid-induced androgen deficiency and the efficacy of testosterone therapy, with a particular focus on its anti-nociceptive effects.</p><p><strong>Methods: </strong>Original and review articles on opioid-induced male androgen deficiency published from 1950 through June 2024 were retrieved from PubMed using the key terms \"opioids,\" \"hypogonadism,\" \"low testosterone,\" and \"testosterone therapy.\" References within the retrieved publications were also researched.</p><p><strong>Results: </strong>Opioids suppress the gonadal axis mainly by inhibiting GnRH synthesis and secretion. The prevalence of opioid-induced androgen deficiency in men varies between 20% and 80% and is influenced by the type of opioid used, duration of exposure, age of the cohort, and how low testosterone was defined. Limited data from clinical trials suggest that testosterone therapy improves libido, body composition, and certain domains of quality of life. Early evidence also suggests that testosterone has anti-nociceptive properties, confirming findings from preclinical and population studies.</p><p><strong>Conclusion: </strong>Chronic opioid use is a common but underappreciated cause of androgen deficiency in men. There is a need to raise awareness among clinicians regarding this adverse effect of opioid use. Testosterone therapy could be considered in men with unequivocal androgen deficiency after a thorough clinical evaluation. Ongoing clinical trials will shed further light on the efficacy of testosterone therapy, particularly regarding its anti-nociceptive effects.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466794","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":"Loss of lncRNAs 1700101O22Rik and 1700027A15Rik causes sperm malformation and subfertility.","authors":"Shijue Dong, Ziyi Cai, Jingyan Yu, Min Liang, Yang Zhou, Mengqian Ding, Xuhui Zeng, Xiaoning Zhang","doi":"10.1111/andr.70011","DOIUrl":"https://doi.org/10.1111/andr.70011","url":null,"abstract":"<p><strong>Background: </strong>The testis is a key reservoir of long non-coding RNAs, yet their physiological roles in male reproduction remain debated. Notably, long non-coding RNAs 1700101O22Rik (22Rik) and 1700027A15Rik (15Rik) are uniquely expressed in the mouse testis. Previous research indicates that both 22Rik and 15Rik play roles in male reproductive processes; however, it is still unclear whether their effects on fertility are cumulative or compensatory.</p><p><strong>Objectives: </strong>To investigate the influence of simultaneous deletion of 22Rik and 15Rik on male reproduction and whether there are additive effects.</p><p><strong>Materials and methods: </strong>22Rik and 15Rik knockout mice were generated using CRISPR-Cas9, and double knockout mice were obtained through co-caging. To investigate reproductive phenotypes, we utilized computer-aided sperm analysis, acrosome reaction assessments, in vitro fertilization techniques, and sperm morphology analysis. Additionally, RNA sequencing and RNA binding protein immunoprecipitation were employed to explore the regulatory mechanisms of 22Rik and 15Rik.</p><p><strong>Results: </strong>The simultaneous deletion of 22Rik and 15Rik led to abnormal sperm morphology, impaired acrosome reaction, and reduced in vitro fertilization. Sperm count and fertility were also decreased in double knockout male mice. Compared to the knockout of long non-coding RNA 22Rik, reproductive abnormalities were somewhat exacerbated but largely similar to those observed with 15Rik knockout alone because of shared targeted genes, particularly Y chromosome-linked genes. Additionally, these abnormal phenotypes may be linked to reduced expression of transition protein 1 and dysfunction of the HSF2‒Rik22‒Rik15 complex in double knockout mice.</p><p><strong>Discussion and conclusion: </strong>Our study demonstrates for the first time that simultaneous knockout of these two long non-coding RNAs adversely affects sperm morphology and function by disrupting the HSF2‒Rik22‒Rik15 complex. Moreover, many overlapping regulated genes suggest that 22Rik and 15Rik may share similar regulatory mechanisms at the molecular level. This research sheds light on the causes and mechanisms behind sperm malformation and impaired male fertility.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412986","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":"First application of three-dimensional light sheet fluorescence microscopy to human testicular tumors: New perspectives in histopathology.","authors":"Diana Pinkert-Leetsch, Ahmad Kareem, Simon F Merz, Marc Teckentrup, Alexander Fichtner, Felix Bremmer, Jeannine Missbach-Guentner","doi":"10.1111/andr.70009","DOIUrl":"https://doi.org/10.1111/andr.70009","url":null,"abstract":"<p><strong>Background: </strong>Testicular tumors are among the most frequently diagnosed cancers in young men. The consequences of this diagnosis are orchiectomies, severely restricting fertility. For these young patients, a comprehensive diagnostics would be desirable, achieving a refined diagnosis and improved therapeutic patient stratification.</p><p><strong>Objective: </strong>The aim of this study was to use three-dimensional (3D) light sheet fluorescence microscopy (LSFM) to analyze a complete testicular tumor punch at subcellular resolution-allowing a detailed diagnostic assessment of the entire punch.</p><p><strong>Materials and methods: </strong>Tissue punches (3  and 5 mm diameter) were taken from paraffin blocks of four miscellaneous testicular tumors. After deparaffinization and clearing using benzoic acid/benzyl benzoate, a label-free LSFM autofluorescence imaging was performed. In addition, TO-PRO-3 nuclear stain was applied to several punches. After the scan, the samples were embedded in paraffin again and physically sectioned for conventional planar histology.</p><p><strong>Results: </strong>Based on the specific autofluorescence, not only the general morphology of the tumor tissue was identified in LSFM datasets, but also diagnostic features like infiltrations, papillary and pagetoid tumor cell formations, germ cell neoplasia in situ and azoospermia. Subcellular characteristics such as vacuolated cytoplasm and pleomorphic nuclei could be detected at maximum magnification. After nuclear staining, virtual H&E sections were reconstructed from the LSFM data and tomographically visualized across the entire punch. Subsequent histology and immunohistochemistry after LSFM analyses is possible.</p><p><strong>Discussion: </strong>LSFM analysis of testicular tumors enables the detailed 2D/3D analysis of an entire tumor punch for assessment of relevant tumor characteristics due to its intrinsic fluorescence or with specific nuclear staining.</p><p><strong>Conclusion: </strong>LSFM provides the technical basis for the analyses of complete testicular tumor biopsies, thus maximizing the spatial morphological and anatomical information. The subcellular 3D imaging of the tumor has the potential to identify new cancer imaging biomarkers that have additional diagnostic and prognostic value for patients.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397982","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}