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Gender-affirming hormone therapy: Effect on semen quality and use of fertility preservation. 性别确认激素治疗:对精液质量的影响和保留生育能力的使用。
IF 3.4 2区 医学
Andrology Pub Date : 2025-08-21 DOI: 10.1111/andr.70112
Anna Chiara Conflitti, Alessandra Buonacquisto, Gaia Cicolani, Silvia Di Chiano, Marta Ruberto, Francesco Pallotti, Francesco Lombardo, Donatella Paoli
{"title":"Gender-affirming hormone therapy: Effect on semen quality and use of fertility preservation.","authors":"Anna Chiara Conflitti, Alessandra Buonacquisto, Gaia Cicolani, Silvia Di Chiano, Marta Ruberto, Francesco Pallotti, Francesco Lombardo, Donatella Paoli","doi":"10.1111/andr.70112","DOIUrl":"https://doi.org/10.1111/andr.70112","url":null,"abstract":"<p><p>Fertility preservation (FP) is a fundamental part of gender care. Gender-affirming hormone therapy (GAHT) involves the use of drugs that could be potential risk factors for fertility. Therefore, FP is recommended before beginning the gender-affirmation process. This narrative review aims to assess several aspects, mainly concerning the assigned male at birth (AMAB) population. The purpose of this review is to provide an overview of the effects of GAHT on testicular morphology and seminal quality, the use of semen cryopreservation, the desire for parenthood among transgender people, the factors influencing the decision to use fertility preservation (FP) and suggestions for improving clinical practice. A literature search within PubMed was conducted and the results deal with issues such as changes in testicular morphology and semen quality, FP utilization, barriers to treatment, current clinical practice models, and suggestions for improving transgender adolescents access to FP. The results showed that GAHT can have a negative effect on fertility in transgender AMAB subjects. It is therefore recommended to carry out FP before starting such treatment. However, there is low percentage of utilization to FP among transgender adolescents. In deciding whether to pursue FP, they consider many factors: future parenting desires, individual experiences of gender dysphoria, family values around biological parenting, financial considerations, and the availability of fertility information. A discrepancy emerged between the rate of desire to become a parent and the actual rate of FP utilization. The reasons are various, such as cost, and concern in delaying the initiation of treatment. Suggestions for improving clinical practice are also provided from this literature search.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939555","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}
引用次数: 0
Lactate inhibits glucose-induced zigzag motility and enhances linear motility in bull spermatozoa by suppressing glycolysis. 乳酸通过抑制糖酵解来抑制葡萄糖诱导的牛精子之字形运动和增强直线运动。
IF 3.4 2区 医学
Andrology Pub Date : 2025-08-15 DOI: 10.1111/andr.70113
Miraz Md Faizul Hossain, Takahiro Yamanaka, Akter Shahrina, Masanori Koyago, Masayuki Shimada
{"title":"Lactate inhibits glucose-induced zigzag motility and enhances linear motility in bull spermatozoa by suppressing glycolysis.","authors":"Miraz Md Faizul Hossain, Takahiro Yamanaka, Akter Shahrina, Masanori Koyago, Masayuki Shimada","doi":"10.1111/andr.70113","DOIUrl":"https://doi.org/10.1111/andr.70113","url":null,"abstract":"<p><strong>Background: </strong>Energy metabolism and substrate balance are critical determinants of sperm motility and fertility. Linear motility is necessary for sperm forward movement, whereas hyperactivated motility is a prerequisite for fertilization. The preference of metabolic pathways depends on substrate availability which controls sperm motility. However, there are differences in substrate composition in seminal plasma, vagina, uterus and oviducts.</p><p><strong>Objectives: </strong>This study aims to clarify how the spermatozoa maintains its metabolic homeostasis and functions in the presence of glucose and lactate either alone or in combinations.</p><p><strong>Materials and methods: </strong>Fresh bull spermatozoa was incubated with modified human tubal fluid (mHTF) medium containing either no-energy, glucose, lactate, or a combination of glucose and lactate. Sperm motility, kinematics, adenosine triphosphate (ATP) production, mitochondrial membrane potential, glucose incorporation, glycolysis, oxidative phosphorylation (OXPHOS), and acrosome reaction were systematically assessed.</p><p><strong>Results: </strong>Glucose resulted in zigzag motility and lactate induced linear motility. Glucose-derived zigzag motility was suppressed by lactate with increasing lactate concentration in a dose-dependent manner. The addition of lactate with glucose showed higher mitochondrial membrane potential, higher oxygen consumption rate (OCR), and lower extracellular acidification rate (ECAR). Lactate suppressed glucose incorporation in midpiece and tail regions, reduced glycolysis, and shifted sperm metabolism toward OXPHOS which resulted in linear motility and maintained acrosome integrity.</p><p><strong>Discussion: </strong>Lactate played a metabolic and regulatory role in bull sperm metabolism. As a metabolic role, it oxidized through OXPHOS and maintained linear motility. The metabolic changes by lactate suppressed glucose-induced acrosome reactions and maintained linear motility, which might be beneficial for sperm transportation toward the fertilization site of the female reproductive tract and results in successful fertilization.</p><p><strong>Conclusion: </strong>This is a novel finding that explores the regulatory role of lactate over glucose metabolism in bull sperm functionality. Optimum balancing of glucose and lactate maintains the motility and functionality of bull spermatozoa. These outcomes might have substantial implications for the enhancement of sperm preservation techniques, sperm handling, and fertility outcomes.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858816","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}
引用次数: 0
Comparative efficacy of combination therapy including regenerative therapies versus monotherapy for erectile dysfunction: A systematic review and meta-analysis. 包括再生疗法在内的联合疗法与单一疗法治疗勃起功能障碍的疗效比较:一项系统综述和荟萃分析。
IF 3.4 2区 医学
Andrology Pub Date : 2025-08-12 DOI: 10.1111/andr.70108
Alberto Quistini, Giuseppe Fallara, Marco Tozzi, Massimiliano Depalma, Rocco Damiano, Alessandro Palmieri, Fabio Castiglione, Andrea Salonia, Roberto Bianchi, Matteo Ferro, Asif Muneer, Hussain M Alnajjar, Karl H Pang
{"title":"Comparative efficacy of combination therapy including regenerative therapies versus monotherapy for erectile dysfunction: A systematic review and meta-analysis.","authors":"Alberto Quistini, Giuseppe Fallara, Marco Tozzi, Massimiliano Depalma, Rocco Damiano, Alessandro Palmieri, Fabio Castiglione, Andrea Salonia, Roberto Bianchi, Matteo Ferro, Asif Muneer, Hussain M Alnajjar, Karl H Pang","doi":"10.1111/andr.70108","DOIUrl":"https://doi.org/10.1111/andr.70108","url":null,"abstract":"<p><strong>Background and objective: </strong>The Current European Association of Urology guidelines do not provide recommendation for combination of regenerative therapies with standard therapies for erectile dysfunction. The aim of this study was to compare the efficacy of combined regenerative therapy with monotherapy for erectile dysfunction.</p><p><strong>Methods: </strong>A systematic review and meta-analysis were conducted following the 2020 Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. The protocol was registered on PROSPERO (CRD42024522307). Randomized controlled trials and prospective/retrospective studies comparing combination therapies (low-intensity external shockwave therapy, platelet-rich plasma, stem cell therapy with phosphodiesterase-5 inhibitors, or other treatments) with monotherapy were included. Erectile function was assessed using the International Index of Erectile Function-5 and Erection Hardness Scale. Groups were compared using standardized mean difference. Subgroup analyses based on treatment type, erectile dysfunction cause, and follow-up duration were also conducted. Risk of bias was assessed using risk of bias 2 and Robins-I tools.</p><p><strong>Key findings and limitations: </strong>Of 1416 articles screened, eight studies involving 553 patients met the inclusion criteria. All studies included phosphodiesterase-5 inhibitors and low-intensity external shockwave therapy as regenerative treatment, with no studies on stem cell therapy or platelet-rich plasma. After treatment, no significant difference in International Index of Erectile Function scores was found between combination and monotherapy groups. However, subgroup analysis revealed that combination therapy showed a statistically significant improvement compared to low-intensity external shockwave therapy alone (standardized mean difference: 0.61; 95% confidence interval: 0.13‒1.09; p = 0.013). A statistically significant improvement was found in vasculogenic (standardized mean difference: 0.65; p < 0.001) and diabetic cases (standardized mean difference: 1.05; p < 0.001).</p><p><strong>Conclusions and clinical implications: </strong>Combination of phosphodiesterase-5 inhibitors and intensity external shockwave therapy resulted in significant improvement of International Index of Erectile Function compared to intensity external shockwave therapy alone. However, the risk of bias was high because of the low quality of the studies.</p><p><strong>Patient summary: </strong>Combination of phosphodiesterase-5 inhibitor with intensity external shockwave therapy significantly improved erectile function, especially in patients with vasculogenic erectile dysfunction or diabetes.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833782","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}
引用次数: 0
From concept to the clinic: Retinoic acid receptor α antagonist YCT-529, an oral non-hormonal male contraceptive. 从概念到临床:视黄酸受体α拮抗剂YCT-529,口服非激素男性避孕药。
IF 3.4 2区 医学
Andrology Pub Date : 2025-08-12 DOI: 10.1111/andr.70106
Noha Taher, Ehfazul Haque, Gunda I Georg
{"title":"From concept to the clinic: Retinoic acid receptor α antagonist YCT-529, an oral non-hormonal male contraceptive.","authors":"Noha Taher, Ehfazul Haque, Gunda I Georg","doi":"10.1111/andr.70106","DOIUrl":"https://doi.org/10.1111/andr.70106","url":null,"abstract":"<p><p>YCT-529 reversibly reduces sperm counts to infertility levels in mice and non-human primates. Mice mating studies demonstrated 99% effectiveness in preventing pregnancies. YCT-529 has completed a first-in-class, double-blind, placebo-controlled Phase I clinical safety study in men and is currently being investigated in a Phase Ib/IIa clinical study.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833783","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}
引用次数: 0
Oxidative stress and testicular damage induced by chronic exposure to 35.5 GHz millimeter wave radiation in male Wistar rats. 慢性35.5 GHz毫米波辐射对雄性Wistar大鼠氧化应激和睾丸损伤的影响。
IF 3.4 2区 医学
Andrology Pub Date : 2025-08-12 DOI: 10.1111/andr.70107
Rohit Gautam, Neha Jha, Anuj Kumar Tomar, Jay Prakash Nirala, Taruna Arora, Paulraj Rajamani
{"title":"Oxidative stress and testicular damage induced by chronic exposure to 35.5 GHz millimeter wave radiation in male Wistar rats.","authors":"Rohit Gautam, Neha Jha, Anuj Kumar Tomar, Jay Prakash Nirala, Taruna Arora, Paulraj Rajamani","doi":"10.1111/andr.70107","DOIUrl":"https://doi.org/10.1111/andr.70107","url":null,"abstract":"<p><strong>Background: </strong>The widespread usage of millimeter waves (MMW) in different spheres of the public domain necessitates to have a better understanding of any possible health impacts caused by them. The latest example of this is the global implementation of 5G technology.</p><p><strong>Objectives: </strong>The present investigation aimed to study the effects of 35.5 GHz frequency on reproductive parameters of male Wistar rats.</p><p><strong>Methods: </strong>The study employed a randomized controlled design, with animals being assigned to control, sham-exposed, and exposed groups, with six animals in each group (n = 6). The experimental group was exposed to 35.5 GHz frequency for 2 h per day for 60 days. At the end of the exposure period, various sperm parameters such as sperm count, morphology, viability, and sperm mitochondrial activity were evaluated. The evaluation of oxidative stress was done by lipid peroxidation assay in testis homogenate. Superoxide dismutase, total sulfhydryl level, and total antioxidant capacity were assessed in testis homogenate. The DNA damage in the testis was assessed through the comet assay.</p><p><strong>Results: </strong>The results showed a significant decrease in sperm viability and count, as well as morphometric changes in testis histopathology. Lipid peroxidation testis was significantly elevated in the exposed group, while superoxide dismutase (SOD), total sulfhydryl level, and total antioxidant capacity were significantly decreased in the exposed group. The comet assay revealed a significant increase in DNA damage in the exposed group, indicating genotoxic effects.</p><p><strong>Discussion: </strong>The observed changes in sperm parameters, testicular morphology, and oxidative stress markers highlight the potential for testicular tissue damage via oxidative mechanisms. These results underscore the need for further research to elucidate the biological implications of chronic MMW exposure.</p><p><strong>Conclusion: </strong>Chronic exposure to 35.5 GHz frequency may negatively impact male reproductive function and testicular tissue, primarily through mechanisms involving oxidative stress.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833784","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}
引用次数: 0
Genetics of infertility and "assisted fertilization" in the Bible: The case of Abraham and his family. 圣经中不孕症和“辅助受精”的遗传学:亚伯拉罕和他的家人的例子。
IF 3.4 2区 医学
Andrology Pub Date : 2025-08-01 DOI: 10.1111/andr.70103
Manuela Simoni, Frank Tüttelmann, Livio Casarini
{"title":"Genetics of infertility and \"assisted fertilization\" in the Bible: The case of Abraham and his family.","authors":"Manuela Simoni, Frank Tüttelmann, Livio Casarini","doi":"10.1111/andr.70103","DOIUrl":"https://doi.org/10.1111/andr.70103","url":null,"abstract":"<p><p>Couple infertility is a very ancient medical condition. One of the first descriptions of familial infertility/subfertility is contained in the first book of the Bible, Genesis, written in the 10th century BC and reporting tales from the oral tradition even occurred about 800 years earlier. Genesis reports the peculiar case of Abraham and his descendants, Isaac and Jacob, the three patriarchs of Israel. The (favorite) wife of the three of them suffered from primary infertility and, according to Genesis, could reach pregnancy only in late age and for divine intervention. In this paper, we reconstruct the pedigree of Abraham's family on the basis of the biblical narration, which is rich enough of medical details to allow to reconstruct a plausible medical/genetic reason for the cases of infertility reported therein.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764385","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}
引用次数: 0
Rotating shiftwork in men is linked to decreased fecundity, attributable primarily to sperm concentration and vitality: 24-month follow-up in 3425 males of PREBIC cohort. 男性轮班与生育能力下降有关,主要归因于精子浓度和活力:对PREBIC队列的3425名男性进行了24个月的随访。
IF 3.4 2区 医学
Andrology Pub Date : 2025-07-30 DOI: 10.1111/andr.70102
Yimeng Wang, Mengchao He, Xi Ling, Tong Wang, Chenran Yin, Huan Yang, Niya Zhou, Wenzheng Zhou, Qing Chen, Jia Cao
{"title":"Rotating shiftwork in men is linked to decreased fecundity, attributable primarily to sperm concentration and vitality: 24-month follow-up in 3425 males of PREBIC cohort.","authors":"Yimeng Wang, Mengchao He, Xi Ling, Tong Wang, Chenran Yin, Huan Yang, Niya Zhou, Wenzheng Zhou, Qing Chen, Jia Cao","doi":"10.1111/andr.70102","DOIUrl":"https://doi.org/10.1111/andr.70102","url":null,"abstract":"<p><strong>Background: </strong>Previous observational studies investigating the association between shift work and male fecundity employed retrospective designs and reported inconsistent findings. The distinction between rotating and fixed shift work has been noticed but not often taken into consideration in the field of reproductive health. Whether semen parameters played a role in this relationship was also unclear.</p><p><strong>Objective: </strong>This study aimed to prospectively evaluate the association between male rotating shift work and achieving a successful pregnancy, and to assess the contribution of semen parameters to this relationship.</p><p><strong>Materials and methods: </strong>Men reported their work type (rotating shift workers, fixed day workers, and fixed shift workers) and seven semen parameters (semen volume, sperm concentration, total sperm count, progressive motility, total motility, vitality, and normal morphology) were measured. Participants were contacted every 3 months for pregnancy status for up to 24 months or until conception. The rates of achieving a successful pregnancy within 1 year and 2 years were calculated to estimate male fecundity. Cox regression and linear regression were applied to compare the hazard of achieving a pregnancy within 1/2 year and semen parameters among rotating shift workers, fixed day workers, and fixed shift workers. Mediation analysis was applied to examine the contributions of semen parameters to the shiftwork-fecundity association.</p><p><strong>Results: </strong>(1) After adjusting confounders, rotating shift workers had a 16% (HR = 0.84, 95% CI, 0.70-0.99, p = 0.04) and 14% (HR = 0.86, 95% CI, 0.74-1.01, p = 0.06) lower hazard of achieving a pregnancy within 1 year and 2 years, respectively, compared to fixed day workers. (2) Of the seven semen parameters, the rotating shift workers were significantly associated with lower sperm concentration (β = -10.77%, 95% CI, -18.89% to -2.55%, p = 0.01), total sperm count (β = -11.63%, 95% CI, -21.25% to -2.02%, p = 0.02), and vitality (β = -3.86%, 95% CI, -7.00% to -0.72%, p = 0.02) compared to the fixed day workers. No significant difference was found between fixed day workers and fixed shift workers. (3) Sperm concentration accounted for 33.46% and 31.12% of the total effect of the relationship between rotating shift work and lower hazard of achieving a pregnancy within 1 and 2 years. Vitality also mediated this association by 30.79% and 23.59%, respectively.</p><p><strong>Conclusions: </strong>Male rotating shift work was associated with reduced fecundity, primarily attributed to reduced sperm concentration and vitality. The study emphasizes the need for occupational protection and provision of medical care for male workers with rotating shifts.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741007","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}
引用次数: 0
The aporetic dialogs of Modena on gender differences: Is it all about testosterone? Episode III: Mathematics. 摩德纳关于性别差异的悲叹对话:这一切都与睾丸激素有关吗?第三集:数学。
IF 3.4 2区 医学
Andrology Pub Date : 2025-07-28 DOI: 10.1111/andr.70104
Giulia Brigante, Francesco Costantino, Alessio Bellelli, Stefano Boni, Chiara Furini, Rita Cucchiara, Manuela Simoni
{"title":"The aporetic dialogs of Modena on gender differences: Is it all about testosterone? Episode III: Mathematics.","authors":"Giulia Brigante, Francesco Costantino, Alessio Bellelli, Stefano Boni, Chiara Furini, Rita Cucchiara, Manuela Simoni","doi":"10.1111/andr.70104","DOIUrl":"https://doi.org/10.1111/andr.70104","url":null,"abstract":"<p><p>This report is the transcript of what was discussed in a convention at the Endocrinology Unit in Modena, Italy, in the form of the aporetic dialogs of ancient Greece. It is the third episode of a series of four discussions on the differences between males and females, with a multidisciplinary approach. In this work, the role of testosterone in gender differences in the aptitude for mathematics is explored. First, the definitions of mathematical abilities were provided together with any gender difference in the distribution of females and males in science, technology, engineering, and mathematics subjects. A clear predominance of males is evident at most science, technology, engineering, and mathematics education levels, especially in advanced academic careers. Then, the discussants were divided into two groups: group 1, which illustrated the thesis that testosterone promotes the development of logical‒mathematical skills, and group 2, which, in contrast, asserted the inconsistency of a direct role of testosterone in improving cognitive abilities and that socio-cultural factors should be considered on the basis of this gender gap. In the end, an expert referee (a female engineer) tried to resolve the aporia: are the two theories equivalent or is one superior?</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726586","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}
引用次数: 0
Spatial transcriptomics mapping of immune cell and TGFβ signalling pathway heterogeneity in testicular germ cell tumours. 睾丸生殖细胞肿瘤中免疫细胞和tgf - β信号通路异质性的空间转录组学定位
IF 3.2 2区 医学
Andrology Pub Date : 2025-07-22 DOI: 10.1111/andr.70100
Sarah C Moody, Daniela Fietz, Benedict Nathaniel, Mark Frydenberg, Ben Tran, Hans-Christian Schuppe, Kate L Loveland
{"title":"Spatial transcriptomics mapping of immune cell and TGFβ signalling pathway heterogeneity in testicular germ cell tumours.","authors":"Sarah C Moody, Daniela Fietz, Benedict Nathaniel, Mark Frydenberg, Ben Tran, Hans-Christian Schuppe, Kate L Loveland","doi":"10.1111/andr.70100","DOIUrl":"https://doi.org/10.1111/andr.70100","url":null,"abstract":"<p><strong>Background: </strong>Testicular germ cell tumours (TGCTs) are amongst the most common malignancies in young men, and their incidence is increasing worldwide. Tissue heterogeneity hampers efforts to understand how TGCT precursors (termed germ cell neoplasia in situ; GCNIS) emerge and progress, restricting elucidation of new strategies for diagnosis and management.</p><p><strong>Objectives: </strong>This study reports the use of spatial transcriptomic analysis in TGCT tissue sections.</p><p><strong>Materials and methods: </strong>Over 90 regions of interest (ROIs) were identified in sections from four TGCT patients' samples, three with non-seminoma, one seminoma. Transcripts in each ROI were sequenced and examined using the NanoString GeoMx spatial whole transcriptomics workflow, the values normalised and analysed using Degust RNA-Seq and Ingenuity Pathway Analysis software.</p><p><strong>Results: </strong>The distribution and expression of functional markers in specific cell types was used to map individual tumours, GCNIS, and tumour-adjacent regions. Significant heterogeneity in TGCTs and surrounding areas is documented between patients and across different regions in the same tumour. Immune cell-related transcripts encoding macrophage, T cell, B cell, natural killer cell, dendritic cells and neutrophil subsets were identified as contributing substantially to tumour heterogeneity. Assessment of ROIs containing GCNIS and areas immediately adjacent from two individual non-seminoma tumour samples identified the TGFβ family as contributing to upstream regulation of transcripts in both patients; known activin A target genes were differentially expressed between the GCNIS and microenvironment ROIs. In addition, two discrete tumour areas within the seminoma sample displayed distinct transcript profiles, one featuring higher levels of immune cell-related transcripts, and the other TGFβ superfamily transcripts.</p><p><strong>Conclusion: </strong>These findings highlight aspects of the complex challenge faced while seeking therapeutic targets to enable tumour spread restriction. However, these outcomes reinforce knowledge that TGFβ family members can influence seminoma fate and provide new evidence of their potential contribution to the transition of GCNIS cells into tumours.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681900","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}
引用次数: 0
Uncovering novel therapeutic targets for premature ejaculation from gut microbiota: A prospective high-throughput sequencing study. 从肠道微生物群中发现早泄的新治疗靶点:一项前瞻性高通量测序研究。
IF 3.2 2区 医学
Andrology Pub Date : 2025-07-22 DOI: 10.1111/andr.70099
Guangdong Hou, Geng Zhang, Yu Zheng, Siyan Zhang, Massimo Federici, Ping Meng, Fuli Wang, Bo Zhang, Emmanuele A Jannini, Jianlin Yuan
{"title":"Uncovering novel therapeutic targets for premature ejaculation from gut microbiota: A prospective high-throughput sequencing study.","authors":"Guangdong Hou, Geng Zhang, Yu Zheng, Siyan Zhang, Massimo Federici, Ping Meng, Fuli Wang, Bo Zhang, Emmanuele A Jannini, Jianlin Yuan","doi":"10.1111/andr.70099","DOIUrl":"https://doi.org/10.1111/andr.70099","url":null,"abstract":"<p><strong>Background: </strong>Despite being the only approved oral therapy for premature ejaculation (PE), dapoxetine faces high discontinuation rates because of its suboptimal efficacy. Given that the role of gut microbiota in PE treatment has remained unexplored, we aim to investigate gut microbiota that may reflect the efficacy of dapoxetine.</p><p><strong>Methods: </strong>Clinical data and fecal samples were collected from patients with lifelong PE before treatment. Gut microbiota was profiled via 16S rDNA sequencing, and differential microbiota between effective and ineffective groups were identified with the LEfSe method. To explore potential links between gut dysbiosis and efficacy, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway functional predictions were performed with the PICRUSt2 method. Efficacy was assessed using the Clinical Global Impression of Change (CGIC) scale, with scores ≥1 defined as the effective group.</p><p><strong>Results: </strong>In the effective group, Erysipelotrichaceae_UCG_003, Parabacteroides_distasonis, and Prevotella_7_unclassified were significantly more prevalent, while Collinsella aerofaciens was less abundant. Their abundance was significantly correlated with CGIC scores, with correlation coefficients of 0.331, 0.250, 0.288, and ‒0.345, respectively. The discriminatory abilities of the four differential microbiota were 0.654, 0.669, 0.701, and 0.615, respectively. Incorporating them significantly improved the accuracy of the model predicting efficacy (0.796 vs. 0.738), which further suggests that modulating microbiota could be a novel strategy for PE treatment. The predicted gene abundance in the arachidonic acid metabolism pathway was significantly elevated in the effective group, indicating that dapoxetine's mechanism may also involve modulating this pathway.</p><p><strong>Conclusions: </strong>This study identified gut microbiota associated with the efficacy of dapoxetine for the first time. Targeted modulation of specific gut microbiota may provide a novel strategy for PE treatment.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681901","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}
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