Pub Date : 2025-07-07DOI: 10.1038/s41585-025-01062-2
R. Clayton Edenfield, Jasper C. Bash, Lyndsey E. Shorey-Kendrick, Rahul J. D’Mello, Travis L. Rice-Stitt, Olivia L. Hagen, Jason A. Graham, Kyle E. Orwig, Charles A. Easley, Jason C. Hedges, Carol B. Hanna, Jamie O. Lo
Male fertility is complex and influenced by genetic, hormonal, environmental and lifestyle factors. However, limitations to human studies necessitate the use of reliable preclinical models to better understand the underlying mechanisms of male fertility. Rhesus macaques (Macaca mulatta), with their close genetic and physiological similarities to humans, offer an invaluable model for male reproductive health studies. The suitability of rhesus macaques for studying male infertility is based on similarities in spermatogenesis, hormonal cycles and the way in which assisted reproductive technologies can be applied, and key differences and similarities between human and rhesus macaque sperm structure, function and cryopreservation techniques highlight the translational potential of findings derived from macaque models. Furthermore, insights into the epigenetic and proteomic characteristics of sperm in both species improve understanding of how these findings can help to advance clinical diagnostics, male contraception and fertility preservation and illuminate the regulatory omics of normal reproduction. Thus, the rhesus macaque model offers critical insights into male fertility and studies in this species could contribute to advances in therapies for male infertility. Non-human primates, especially the rhesus macaque, provide a good preclinical model for research into male fertility, owing to their physiological and genetic similarities to humans. In this article, the authors examine the value and limitations of using non-human primates in studies to improve understanding of spermatogenesis, reproductive endocrinology and innovations in assisted reproductive technologies.
{"title":"Non-human primates as a translational model for the study of male reproductive health","authors":"R. Clayton Edenfield, Jasper C. Bash, Lyndsey E. Shorey-Kendrick, Rahul J. D’Mello, Travis L. Rice-Stitt, Olivia L. Hagen, Jason A. Graham, Kyle E. Orwig, Charles A. Easley, Jason C. Hedges, Carol B. Hanna, Jamie O. Lo","doi":"10.1038/s41585-025-01062-2","DOIUrl":"10.1038/s41585-025-01062-2","url":null,"abstract":"Male fertility is complex and influenced by genetic, hormonal, environmental and lifestyle factors. However, limitations to human studies necessitate the use of reliable preclinical models to better understand the underlying mechanisms of male fertility. Rhesus macaques (Macaca mulatta), with their close genetic and physiological similarities to humans, offer an invaluable model for male reproductive health studies. The suitability of rhesus macaques for studying male infertility is based on similarities in spermatogenesis, hormonal cycles and the way in which assisted reproductive technologies can be applied, and key differences and similarities between human and rhesus macaque sperm structure, function and cryopreservation techniques highlight the translational potential of findings derived from macaque models. Furthermore, insights into the epigenetic and proteomic characteristics of sperm in both species improve understanding of how these findings can help to advance clinical diagnostics, male contraception and fertility preservation and illuminate the regulatory omics of normal reproduction. Thus, the rhesus macaque model offers critical insights into male fertility and studies in this species could contribute to advances in therapies for male infertility. Non-human primates, especially the rhesus macaque, provide a good preclinical model for research into male fertility, owing to their physiological and genetic similarities to humans. In this article, the authors examine the value and limitations of using non-human primates in studies to improve understanding of spermatogenesis, reproductive endocrinology and innovations in assisted reproductive technologies.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"22 11","pages":"756-774"},"PeriodicalIF":14.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-04DOI: 10.1038/s41585-025-01056-0
Prerna R. Nepali, Ahmed Eraky, Kennedy E. Okhawere, Navneet Dogra, Reza Mehrazin, Ketan Badani, Natasha Kyprianou
Non-clear cell renal cell carcinomas (nccRCC) include diverse subtypes such as papillary, oncocytic and chromophobe, collecting duct, molecularly defined and other rare histological subtypes, each associated with unique clinical, pathological, genetic and molecular features as well as therapeutic challenges. Surgical resection remains the primary approach for the treatment of localized nccRCC but optimal outcomes depend on tumour stage and the patient’s overall health. Clinically established treatment guidelines tailored for patients diagnosed with nccRCC are limited owing to the molecular and histological heterogeneity of nccRCC. Progress has been made in systemic therapy for metastatic disease but nccRCC treatment still poses challenges as patients experience variable treatment responses to immunotherapy, targeted therapies, chemotherapy and some combination strategies. Molecular biomarkers as well as established techniques, such as immunohistochemical and genetic analysis, have a crucial role in early detection, prognosis prediction and personalization of targeted therapies for nccRCC. The increasing identification of potential signatures and actionable molecular targets will aid in the clinical decision-making for patients diagnosed with these rare tumours towards optimization of the therapeutic response and treatment outcomes. This Review discusses the different subtypes of non-clear cell renal cell carcinoma in terms of molecular, genetic and clinicopathological characteristics as well as response to therapy. The authors highlight challenges associated with the rarity and heterogeneity of this subset of tumours and how investing in future research to find reliable biomarkers will be essential to improve patient outcomes.
{"title":"Molecular and therapeutic landscape of non-clear cell renal carcinoma","authors":"Prerna R. Nepali, Ahmed Eraky, Kennedy E. Okhawere, Navneet Dogra, Reza Mehrazin, Ketan Badani, Natasha Kyprianou","doi":"10.1038/s41585-025-01056-0","DOIUrl":"10.1038/s41585-025-01056-0","url":null,"abstract":"Non-clear cell renal cell carcinomas (nccRCC) include diverse subtypes such as papillary, oncocytic and chromophobe, collecting duct, molecularly defined and other rare histological subtypes, each associated with unique clinical, pathological, genetic and molecular features as well as therapeutic challenges. Surgical resection remains the primary approach for the treatment of localized nccRCC but optimal outcomes depend on tumour stage and the patient’s overall health. Clinically established treatment guidelines tailored for patients diagnosed with nccRCC are limited owing to the molecular and histological heterogeneity of nccRCC. Progress has been made in systemic therapy for metastatic disease but nccRCC treatment still poses challenges as patients experience variable treatment responses to immunotherapy, targeted therapies, chemotherapy and some combination strategies. Molecular biomarkers as well as established techniques, such as immunohistochemical and genetic analysis, have a crucial role in early detection, prognosis prediction and personalization of targeted therapies for nccRCC. The increasing identification of potential signatures and actionable molecular targets will aid in the clinical decision-making for patients diagnosed with these rare tumours towards optimization of the therapeutic response and treatment outcomes. This Review discusses the different subtypes of non-clear cell renal cell carcinoma in terms of molecular, genetic and clinicopathological characteristics as well as response to therapy. The authors highlight challenges associated with the rarity and heterogeneity of this subset of tumours and how investing in future research to find reliable biomarkers will be essential to improve patient outcomes.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"22 11","pages":"735-755"},"PeriodicalIF":14.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-02DOI: 10.1038/s41585-025-01057-z
Olivier Cussenot
Use of spatial transcriptomics has helped to create a functional map of cellular organization in the healthy and tumoural human prostate, creating new opportunities for understanding age-related prostatic diseases.
{"title":"Mapping the human prostate at the cellular level","authors":"Olivier Cussenot","doi":"10.1038/s41585-025-01057-z","DOIUrl":"https://doi.org/10.1038/s41585-025-01057-z","url":null,"abstract":"Use of spatial transcriptomics has helped to create a functional map of cellular organization in the healthy and tumoural human prostate, creating new opportunities for understanding age-related prostatic diseases.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"199 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-02DOI: 10.1038/s41585-025-01064-0
Marie-Pier St-Laurent, Peter C. Black
Bladder cancer is a biologically heterogeneous disease, and ongoing efforts in biomarker research aim to support personalized treatment approaches. Circulating tumour DNA is approaching clinical integration through prospective trials, whereas other markers remain investigational owing to technical limitations, inconsistent findings and lack of validation. Rigorous biomarker-driven trials and cost-effectiveness studies are needed to enable the integration of molecular tools into routine practice. Biomarkers might ultimately lead to rational treatment de-escalation or escalation, improving outcomes while minimizing harm and cost.
{"title":"Promise without practice — charting the path forward for bladder cancer biomarkers","authors":"Marie-Pier St-Laurent, Peter C. Black","doi":"10.1038/s41585-025-01064-0","DOIUrl":"https://doi.org/10.1038/s41585-025-01064-0","url":null,"abstract":"Bladder cancer is a biologically heterogeneous disease, and ongoing efforts in biomarker research aim to support personalized treatment approaches. Circulating tumour DNA is approaching clinical integration through prospective trials, whereas other markers remain investigational owing to technical limitations, inconsistent findings and lack of validation. Rigorous biomarker-driven trials and cost-effectiveness studies are needed to enable the integration of molecular tools into routine practice. Biomarkers might ultimately lead to rational treatment de-escalation or escalation, improving outcomes while minimizing harm and cost.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"11 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-25DOI: 10.1038/s41585-025-01063-1
Rajvinder Khasriya, Harry Horsley
Despite recognized sex-based differences in healthcare requirements, women continue to experience substantial disparities in treatment, diagnosis and research. This ‘gender health gap’ manifests through increased emergency wait times, dismissal of symptoms and inadequate research prioritization. Patient advocacy groups have emerged as powerful forces for change, successfully lobbying governments and raising awareness through social media. Addressing these disparities requires increased research funding, sex-specific study designs, improved medical education curricula and continued patient advocacy.
{"title":"Why women are not treated equally in healthcare and what can be done","authors":"Rajvinder Khasriya, Harry Horsley","doi":"10.1038/s41585-025-01063-1","DOIUrl":"https://doi.org/10.1038/s41585-025-01063-1","url":null,"abstract":"Despite recognized sex-based differences in healthcare requirements, women continue to experience substantial disparities in treatment, diagnosis and research. This ‘gender health gap’ manifests through increased emergency wait times, dismissal of symptoms and inadequate research prioritization. Patient advocacy groups have emerged as powerful forces for change, successfully lobbying governments and raising awareness through social media. Addressing these disparities requires increased research funding, sex-specific study designs, improved medical education curricula and continued patient advocacy.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"90 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-20DOI: 10.1038/s41585-025-01055-1
Daniel J. Benedetti, Nicholas G. Cost, Peter F. Ehrlich, Nicholas Evageliou, Elizabeth Fialkowski, Lauren N. Parsons, Kelly L. Vallance, Lindsay A. Renfro, Andrew L. Hong, Jennifer H. Aldrink, Luke Pater, Arnold C. Paulino, Jesse K. Sandberg, Ethan A. Smith, Amy L. Treece, Jeffrey S. Dome, James I. Geller, Elizabeth A. Mullen
Patients with Wilms tumour have benefited from the results of decades of large collaborative clinical trials, leading to improved care. In the National Wilms Tumor Study Group and now Children’s Oncology Group (COG) trials, risk stratification evolved and expanded with each generation of studies and, therefore, ensuring that each patient receives the appropriate therapy has become increasingly complex. A new risk stratification system has been developed that forms the basis of the upcoming COG favourable-histology Wilms tumour (FHWT) study. Topics of diagnostic and prognostic uncertainty, such as the findings of tumour pulmonary emboli or extra-abdominal lymphadenopathy at diagnosis, will be integrated into the central review determination of staging of FHWT by committee consensus to facilitate clinical classification for therapeutic studies. Clear documentation of the elements of current risk stratification are of particular importance as refinement of the classification of patients with FHWT continues in an effort to optimize research, personalize treatment and provide an educational resource. In this Consensus Statement, the authors describe the details of the evolution of the risk-based treatment of favourable-histology Wilms tumour (FHWT) and outline the rationale for the new risk stratification that will be used in the now open Children’s Oncology Group therapeutic trial for FHWT, AREN2231.
{"title":"Updated favourable-histology Wilms tumour risk stratification: rationale for future Children’s Oncology Group clinical trials","authors":"Daniel J. Benedetti, Nicholas G. Cost, Peter F. Ehrlich, Nicholas Evageliou, Elizabeth Fialkowski, Lauren N. Parsons, Kelly L. Vallance, Lindsay A. Renfro, Andrew L. Hong, Jennifer H. Aldrink, Luke Pater, Arnold C. Paulino, Jesse K. Sandberg, Ethan A. Smith, Amy L. Treece, Jeffrey S. Dome, James I. Geller, Elizabeth A. Mullen","doi":"10.1038/s41585-025-01055-1","DOIUrl":"10.1038/s41585-025-01055-1","url":null,"abstract":"Patients with Wilms tumour have benefited from the results of decades of large collaborative clinical trials, leading to improved care. In the National Wilms Tumor Study Group and now Children’s Oncology Group (COG) trials, risk stratification evolved and expanded with each generation of studies and, therefore, ensuring that each patient receives the appropriate therapy has become increasingly complex. A new risk stratification system has been developed that forms the basis of the upcoming COG favourable-histology Wilms tumour (FHWT) study. Topics of diagnostic and prognostic uncertainty, such as the findings of tumour pulmonary emboli or extra-abdominal lymphadenopathy at diagnosis, will be integrated into the central review determination of staging of FHWT by committee consensus to facilitate clinical classification for therapeutic studies. Clear documentation of the elements of current risk stratification are of particular importance as refinement of the classification of patients with FHWT continues in an effort to optimize research, personalize treatment and provide an educational resource. In this Consensus Statement, the authors describe the details of the evolution of the risk-based treatment of favourable-histology Wilms tumour (FHWT) and outline the rationale for the new risk stratification that will be used in the now open Children’s Oncology Group therapeutic trial for FHWT, AREN2231.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"22 11","pages":"775-788"},"PeriodicalIF":14.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41585-025-01055-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-18DOI: 10.1038/s41585-025-01060-4
Louise Lloyd
{"title":"Turning back time in the testes","authors":"Louise Lloyd","doi":"10.1038/s41585-025-01060-4","DOIUrl":"10.1038/s41585-025-01060-4","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"22 7","pages":"409-409"},"PeriodicalIF":14.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-16DOI: 10.1038/s41585-025-01061-3
Louise Lloyd
{"title":"Pivotal role of PPARγ in UTO","authors":"Louise Lloyd","doi":"10.1038/s41585-025-01061-3","DOIUrl":"10.1038/s41585-025-01061-3","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"22 7","pages":"409-409"},"PeriodicalIF":14.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-16DOI: 10.1038/s41585-025-01058-y
Raghav Khanna, Nicholas Raison, Alejandro Granados, Sebastien Ourselin, Giorgio Gandaglia, Alberto Briganti, Francesco Montorsi, Prokar Dasgupta
Quantum computing can revolutionize surgery by accelerating the training of artificial intelligence models on large, diverse datasets, advancing robotic autonomy and facilitating a detailed study of biological structures and materials on a very minute scale. Substantial technical, financial and regulatory challenges must be overcome for the successful implementation of quantum computing in urology.
{"title":"Quantum computing in surgery and urology — taking a quantum leap","authors":"Raghav Khanna, Nicholas Raison, Alejandro Granados, Sebastien Ourselin, Giorgio Gandaglia, Alberto Briganti, Francesco Montorsi, Prokar Dasgupta","doi":"10.1038/s41585-025-01058-y","DOIUrl":"10.1038/s41585-025-01058-y","url":null,"abstract":"Quantum computing can revolutionize surgery by accelerating the training of artificial intelligence models on large, diverse datasets, advancing robotic autonomy and facilitating a detailed study of biological structures and materials on a very minute scale. Substantial technical, financial and regulatory challenges must be overcome for the successful implementation of quantum computing in urology.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 1","pages":"2-3"},"PeriodicalIF":14.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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