Pub Date : 2025-11-11DOI: 10.1038/s41585-025-01109-4
Maddison L Graffeo,Jessica E M Dunleavy,Brendan J Houston,Moira K O'Bryan
The sperm tail is a modified motile cilium analogous to those found in tissues including the lung and brain. They have been evolutionarily sculpted to optimize motility and, therefore, fertility, through the dynamic and challenging environment of the female reproductive tract. Sperm tails are composed of three structurally distinct regions: the midpiece, the principal piece and the end piece. The most proximal region - the midpiece - is surrounded by a mitochondrial sheath, which has been proposed to provide structural integrity and ATP as fuel for sperm tail movement. Despite the main phases of mitochondrial sheath assembly being described, the specific biological mechanisms that underpin its formation and maturation remain poorly defined and, in many cases, unknown. Moreover, emerging evidence has highlighted that the precise contribution of the mitochondrial sheath to energy production in sperm has been misunderstood. ATP generation via glycolysis and mitochondrial respiration, previously believed to be physically uncoupled, engage in crosstalk to maximize sperm function, competition and overall fertility. Understanding these processes could not only provide vital insights into the aetiology of male infertility and offer targets for contraceptive development but could also provide insights into mechanisms of relevance to other tissues in which mitochondrial dynamics is challenging to monitor.
{"title":"Sperm mitochondrial sheath formation - how and why?","authors":"Maddison L Graffeo,Jessica E M Dunleavy,Brendan J Houston,Moira K O'Bryan","doi":"10.1038/s41585-025-01109-4","DOIUrl":"https://doi.org/10.1038/s41585-025-01109-4","url":null,"abstract":"The sperm tail is a modified motile cilium analogous to those found in tissues including the lung and brain. They have been evolutionarily sculpted to optimize motility and, therefore, fertility, through the dynamic and challenging environment of the female reproductive tract. Sperm tails are composed of three structurally distinct regions: the midpiece, the principal piece and the end piece. The most proximal region - the midpiece - is surrounded by a mitochondrial sheath, which has been proposed to provide structural integrity and ATP as fuel for sperm tail movement. Despite the main phases of mitochondrial sheath assembly being described, the specific biological mechanisms that underpin its formation and maturation remain poorly defined and, in many cases, unknown. Moreover, emerging evidence has highlighted that the precise contribution of the mitochondrial sheath to energy production in sperm has been misunderstood. ATP generation via glycolysis and mitochondrial respiration, previously believed to be physically uncoupled, engage in crosstalk to maximize sperm function, competition and overall fertility. Understanding these processes could not only provide vital insights into the aetiology of male infertility and offer targets for contraceptive development but could also provide insights into mechanisms of relevance to other tissues in which mitochondrial dynamics is challenging to monitor.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"110 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491463","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 : 2025-11-10DOI: 10.1038/s41585-025-01107-6
Sola Adeleke, Joao R. Galante, Yishen Wang, Gurdip Azad, Simon Wan, Athar Haroon, Diletta Bianchini, Jamshed Bomanji, Michael S. Hofman, Travis S. Young, Gary J. R. Cook
{"title":"Emerging evidence for sequencing and combining PSMA-based therapies in prostate cancer","authors":"Sola Adeleke, Joao R. Galante, Yishen Wang, Gurdip Azad, Simon Wan, Athar Haroon, Diletta Bianchini, Jamshed Bomanji, Michael S. Hofman, Travis S. Young, Gary J. R. Cook","doi":"10.1038/s41585-025-01107-6","DOIUrl":"https://doi.org/10.1038/s41585-025-01107-6","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"2 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477817","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 : 2025-11-10DOI: 10.1038/s41585-025-01104-9
Marc Carceles-Cordon, Veronica Rodriguez-Bravo, Daniel P. Petrylak, Josep Domingo-Domenech
{"title":"20 years of taxane therapy in prostate cancer — the past, present and future","authors":"Marc Carceles-Cordon, Veronica Rodriguez-Bravo, Daniel P. Petrylak, Josep Domingo-Domenech","doi":"10.1038/s41585-025-01104-9","DOIUrl":"https://doi.org/10.1038/s41585-025-01104-9","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"70 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145484858","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 : 2025-11-07DOI: 10.1038/s41585-025-01108-5
Michael George, Susan Wong, Raj Mathur, Nikolaos Tsampras, Alexander Lewis, Ian Pearce, Theodora Stasinou, Vaibhav Modgil
{"title":"Persistent Müllerian duct syndrome — a rare but important cause of male factor infertility","authors":"Michael George, Susan Wong, Raj Mathur, Nikolaos Tsampras, Alexander Lewis, Ian Pearce, Theodora Stasinou, Vaibhav Modgil","doi":"10.1038/s41585-025-01108-5","DOIUrl":"https://doi.org/10.1038/s41585-025-01108-5","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"1 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145461317","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 : 2025-11-07DOI: 10.1038/s41585-025-01106-7
Rui M Bernardino,João Lobo,Jihad Kaouk,Theodorus van der Kwast,Susan Prendeville,Fabio Zanotti,Lorenzo Bianchi,Alberto Martini,Pawel Rajwa,Veeru Kasivisvanathan,Giancarlo Marra,Neil Fleshner,
Atypical intraductal proliferation (AIP) is considered a borderline lesion, characterized by architectural complexity and cytological atypia greater than that seen in high-grade prostatic intraepithelial neoplasia, but insufficient to fulfil the diagnostic criteria for intraductal carcinoma (IDC). Consequently, AIP remains diagnostically challenging, and the clinical significance of this lesion is still uncertain. Emerging evidence suggests that AIP in prostate biopsy specimens is a strong predictor of unsampled IDC and other adverse pathological features, warranting reconsideration of the AIP role in prostate cancer risk stratification. Results from prospective and molecular studies indicate that AIP frequently coexists with intermediate-risk prostate cancer and shares molecular alterations with IDC, such as PTEN loss and ERG overexpression, reinforcing AIP potential as a marker of occult aggressive disease. Considering the growing emphasis on precision diagnostics and active surveillance in prostate cancer management, understanding the implications of AIP is particularly relevant.
{"title":"Atypical intraductal proliferation in prostate biopsy - a diagnostic grey zone with clinical implications.","authors":"Rui M Bernardino,João Lobo,Jihad Kaouk,Theodorus van der Kwast,Susan Prendeville,Fabio Zanotti,Lorenzo Bianchi,Alberto Martini,Pawel Rajwa,Veeru Kasivisvanathan,Giancarlo Marra,Neil Fleshner, ","doi":"10.1038/s41585-025-01106-7","DOIUrl":"https://doi.org/10.1038/s41585-025-01106-7","url":null,"abstract":"Atypical intraductal proliferation (AIP) is considered a borderline lesion, characterized by architectural complexity and cytological atypia greater than that seen in high-grade prostatic intraepithelial neoplasia, but insufficient to fulfil the diagnostic criteria for intraductal carcinoma (IDC). Consequently, AIP remains diagnostically challenging, and the clinical significance of this lesion is still uncertain. Emerging evidence suggests that AIP in prostate biopsy specimens is a strong predictor of unsampled IDC and other adverse pathological features, warranting reconsideration of the AIP role in prostate cancer risk stratification. Results from prospective and molecular studies indicate that AIP frequently coexists with intermediate-risk prostate cancer and shares molecular alterations with IDC, such as PTEN loss and ERG overexpression, reinforcing AIP potential as a marker of occult aggressive disease. Considering the growing emphasis on precision diagnostics and active surveillance in prostate cancer management, understanding the implications of AIP is particularly relevant.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"103 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462022","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 : 2025-10-30DOI: 10.1038/s41585-025-01098-4
Martin Egger, Vincent D. D’Andrea, Clara Steiner, Nnamdi O. Onochie, Timothy N. Clinton, Chong-Xian Pan, Adam S. Kibel, Cheryl T. Lee, Kent W. Mouw, Matthew Mossanen
{"title":"Optimizing local control in the surgical management of bladder cancer","authors":"Martin Egger, Vincent D. D’Andrea, Clara Steiner, Nnamdi O. Onochie, Timothy N. Clinton, Chong-Xian Pan, Adam S. Kibel, Cheryl T. Lee, Kent W. Mouw, Matthew Mossanen","doi":"10.1038/s41585-025-01098-4","DOIUrl":"https://doi.org/10.1038/s41585-025-01098-4","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"3 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145396910","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 : 2025-10-13DOI: 10.1038/s41585-025-01095-7
Dmitry Ratner,Jason L Vassy
Interest in using polygenic scores (PGS) to improve the risk stratification for and early detection of prostate cancer is considerable. Despite the absence of clinical guidelines for the use of prostate cancer PGS in patient care, existing and emerging standards for the clinical translation and reporting of genetic testing generally and PGS specifically provide a relevant framework to help guide these efforts. This framework is intended to harmonize advances in the development of PGS clinical assays and standardization of PGS reporting in the context of prostate cancer PGS specifically. The analytical and clinical validity of prostate cancer PGS have been progressively refined, but evidence firmly establishing clinical utility beyond modelling studies is still lacking. Standardized approaches for designing, explaining and reporting prostate cancer PGS are key to accelerating clinical implementation in a manner that would increase access to the benefits of precision prostate cancer screening to patients across ancestry backgrounds.
{"title":"Clinical translation of polygenic scores for prostate cancer screening.","authors":"Dmitry Ratner,Jason L Vassy","doi":"10.1038/s41585-025-01095-7","DOIUrl":"https://doi.org/10.1038/s41585-025-01095-7","url":null,"abstract":"Interest in using polygenic scores (PGS) to improve the risk stratification for and early detection of prostate cancer is considerable. Despite the absence of clinical guidelines for the use of prostate cancer PGS in patient care, existing and emerging standards for the clinical translation and reporting of genetic testing generally and PGS specifically provide a relevant framework to help guide these efforts. This framework is intended to harmonize advances in the development of PGS clinical assays and standardization of PGS reporting in the context of prostate cancer PGS specifically. The analytical and clinical validity of prostate cancer PGS have been progressively refined, but evidence firmly establishing clinical utility beyond modelling studies is still lacking. Standardized approaches for designing, explaining and reporting prostate cancer PGS are key to accelerating clinical implementation in a manner that would increase access to the benefits of precision prostate cancer screening to patients across ancestry backgrounds.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"120 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283445","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 : 2025-10-13DOI: 10.1038/s41585-025-01099-3
Henry H Woo
{"title":"A urologist as a urological patient.","authors":"Henry H Woo","doi":"10.1038/s41585-025-01099-3","DOIUrl":"https://doi.org/10.1038/s41585-025-01099-3","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"19 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283444","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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