Nature Reviews Urology最新文献

{"title":"Revisiting the dual role of androgens and oestrogens in mammalian sex differentiation with a focus on genitalia","authors":"Emilie Elmelund, Monica K. Draskau, Melanie K. Stewart, Deidre M. Mattiske, Andrew J. Pask, Terje Svingen","doi":"10.1038/s41585-026-01132-z","DOIUrl":"10.1038/s41585-026-01132-z","url":null,"abstract":"Androgen signalling is the primary driver of male sexual differentiation in mammals, directing masculinization during a crucial fetal window. In male fetuses, high levels of fetal androgens, mainly from the testes, promote male reproductive tract development through androgen receptor activation, whereas low levels of androgens in female fetuses enable the development along the female pathway. This androgen-centric view of reproductive development has long dominated the field, casting oestrogens as passive bystanders. However, both historical and emerging evidence challenges this narrative, pointing to an active role of oestrogens in shaping reproductive development through complex, tissue-specific interactions with androgen pathways. Oestrogen receptors are expressed in developing reproductive tissues of both sexes, and disruptions in oestrogen signalling — shown in genetic and pharmacological models — can lead to reproductive abnormalities. Oestrogens might counteract androgen action at the tissue level and modulate androgen receptor expression, independently of effects on androgen production. Moreover, combined exposure to anti-androgens and oestrogenic compounds can amplify developmental disruptions, underscoring the importance of hormonal crosstalk. These findings question the adequacy of an androgen-only model, especially when assessing endocrine disruptors. Understanding the role of oestrogens is essential for interpreting normal development and chemical risks. Reproductive differentiation seems to depend on the integrated balance between androgen and oestrogen pathways, rather than on isolated signals. This Perspective presents historical and emerging evidence supporting a role of oestrogen signalling in male sexual differentiation, challenging the traditional androgen-centric view of reproductive development. Understanding the interplay between these two hormones is important to understanding development and also chemical risk, considering the susceptibility of these systems to disruption from exogenous substances.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 9","pages":"621-629"},"PeriodicalIF":13.6,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350363","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}

{"title":"Urinary tract infections in children","authors":"Preeti P. John, Laura Mike, Indira U. Mysorekar, Juan de Dios Ruiz-Rosado, Menna Clatworthy, Laura Schwartz, Christina Ching, Denise Kimbrough, Nader Shaikh, Luis Braga, Evan Rajadhyaksha, David Hains, Joshua Watson, Brian Becknell","doi":"10.1038/s41585-026-01130-1","DOIUrl":"10.1038/s41585-026-01130-1","url":null,"abstract":"Bacterial urinary tract infections (UTIs) are prevalent in childhood and adolescence. Paediatric UTIs present unique challenges with respect to diagnosis, prevention and management, and the potential for adverse sequelae. Uropathogenic Escherichia coli (UPEC) accounts for the majority of UTIs and is the best studied uropathogen. Novel discoveries have advanced our understanding of host–pathogen interactions, cellular and molecular mechanisms of host defence, and risk factors for UTI recurrence. Emerging evidence also highlights an association of the gut, vaginal and urinary microbiota in influencing UTI risk and recurrence. Yet, key knowledge gaps persist regarding UTI pathogenesis, host susceptibility, optimal diagnostic and management strategies and prevention of UTI recurrence and sequelae, especially in paediatric populations. The development of standardized clinical pathways offers an opportunity to improve care consistency and outcomes by integrating evidence-based practices into routine management. As technologies evolve and understanding deepens, future efforts must integrate host, microbial and clinical insights to optimize UTI prevention and treatment in paediatric populations. In this Review, the authors describe and discuss the unique challenges of paediatric urinary tract infections including diagnosis, prevention and management, potential for adverse sequelae and key knowledge gaps.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 9","pages":"592-606"},"PeriodicalIF":13.6,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147308321","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}

{"title":"Smooth muscle cell plasticity in pelvic organ prolapse","authors":"Hai Tong, Li Lin, Mai Zhang, Zhenglin He, Gengsheng Wang, Lubin Liu","doi":"10.1038/s41585-026-01131-0","DOIUrl":"10.1038/s41585-026-01131-0","url":null,"abstract":"Vaginal wall smooth muscle underpins pelvic support. In pelvic organ prolapse, smooth muscle cells are depleted and shift from a contractile phenotype to remodelling programmes, paralleling stress-induced switching in vascular disease. Defining trajectories and drivers could yield biomarkers and translatable, locally deliverable therapies to curb progression and recurrence.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 7","pages":"425-427"},"PeriodicalIF":13.6,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195313","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}

{"title":"ADT and activation of HGF and WNT axes in double-null prostate cancer","authors":"Dexter Hoi Long Leung, Yao Mawulikplimi Adzavon, Gaeul Chu, Tae Ju Park, Kristoffer Nikias, Cheong-Wun Kim, Chenmiao Liu, Zijie Sun","doi":"10.1038/s41585-026-01129-8","DOIUrl":"10.1038/s41585-026-01129-8","url":null,"abstract":"Prostate cancer remains the most frequently diagnosed malignancy in men worldwide. Most primary prostate cancer cells express the androgen receptor (AR) and rely on androgens for oncogenic growth and progression. Thus, androgen deprivation therapy (ADT) that directly targets AR-expressing prostate cancer cells has been the frontline treatment for advanced prostate cancer. However, ADT inevitably fails in most patients, resulting in castration-resistant prostate cancer development. To inhibit reactivation of AR-promoted tumour progression via residual androgens and altered AR activation, next-generation AR antagonists and inhibitors of androgen biosynthesis were developed to improve clinical outcomes. However, these therapeutic advances also induce heterogeneous resistance phenotypes. Among them, double-null prostate cancer, featuring AR-null and neuroendocrine-null cell properties, occurs in patients treated with abiraterone and enzalutamide. Emerging clinical and experimental evidence demonstrates that current ADT induces HGF and canonical WNT signalling activation, which further elevates nuclear exporting and ribosomal biogenesis to foster tumour lineage plasticity and promote diverse castration-resistant prostate cancer phenotypes and double-null prostate cancer development. These mechanistic insights remain under active investigation, but they provide therapeutic prospects for co-targeting nuclear exporting, ribosomal biosynthesis and other oncogenic pathways in combination with current ADT to forestall the lethal disease. In this Review, the authors discuss the causal role of current androgen deprivation therapy in prostate cancer progression, hormone refractoriness and double-null prostate cancer development. They highlight the underlying regulatory mechanisms by which androgen deprivation therapy elevates hepatocyte growth factor–hepatocyte growth factor receptor (HGF–MET) and WNT–β-catenin signalling, elevating exportin 1 (XPO1) and ribosomal protein activation to induce tumour aggressiveness, metastasis and double-null prostate cancer development.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 8","pages":"533-541"},"PeriodicalIF":13.6,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146150074","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}

{"title":"Fathers matter too: sperm-borne epigenetic messages link paternal exposures to next-generation health","authors":"Sergio Pecorelli, Roberto Lucchini, Luca Lambertini, Giuseppe Novelli","doi":"10.1038/s41585-026-01128-9","DOIUrl":"10.1038/s41585-026-01128-9","url":null,"abstract":"Historically, the contribution of fathers to offspring health has been neglected, with the focus on mothers. However, growing evidence shows the important influence that the environmental factors the fathers experience has on sperm epigenetics and, consequently, the health of the next generation.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 9","pages":"556-557"},"PeriodicalIF":13.6,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146115812","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}

{"title":"Management of surgical menopause in female patients with bladder cancer undergoing radical cystectomy","authors":"Elizabeth Day, Francesco Pio Bizzarri, Ciara Mackenzie, Bernadett Szabados, Adam W. Nelson, Alexandra J. Colquhoun, Matthew J. Perry, John D. Kelly, Niyati Lobo","doi":"10.1038/s41585-026-01124-z","DOIUrl":"10.1038/s41585-026-01124-z","url":null,"abstract":"Radical cystectomy is the gold-standard treatment for patients with muscle-invasive and very high-risk non-muscle-invasive bladder cancer. In female patients, radical cystectomy has traditionally included removal of the uterus, ovaries, fallopian tubes and anterior vaginal wall. The majority of female patients undergoing radical cystectomy are postmenopausal, but a subset of patients are premenopausal and experience surgical menopause as a result of bilateral oophorectomy. Surgical menopause results from an abrupt loss of sex steroid hormones, resulting in symptoms such as vasomotor instability and sexual dysfunction, while also increasing the long-term risk of osteoporosis, cardiovascular disease and cognitive decline. The importance of ovarian preservation during radical cystectomy is increasingly recognized; however, oophorectomy might still be indicated in selected premenopausal patients for oncological control. In these individuals, awareness and management of surgical menopause among urologists is often limited, resulting in avoidable morbidity. Thus, when surgical menopause is unavoidable, patients should be counselled regarding symptom management, cardiovascular risk and bone protection; and appropriate hormonal and non-hormonal therapeutic strategies should be implemented where indicated. Surgical menopause occurs in premenopausal women who undergo radical cystectomy with bilateral oophorectomy to treat bladder cancer. This Review discusses the pathophysiology of surgical menopause in these patients and highlights current strategies to mitigate associated symptoms and long-term health risks.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 7","pages":"468-478"},"PeriodicalIF":13.6,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089099","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}

{"title":"Sperm DNA fragmentation and its influence on mammalian reproduction","authors":"Mehran Dabiri, Dale M. Goss, Ranjith Ramasamy, Mukesh Bhakat, David K. Gardner, Simon P. de Graaf, Majid Ebrahimi Warkiani","doi":"10.1038/s41585-025-01123-6","DOIUrl":"10.1038/s41585-025-01123-6","url":null,"abstract":"Sperm DNA fragmentation is a recognized factor in male infertility with direct implications for embryo development, implantation and pregnancy outcomes. Historically, standard semen analysis has not included assessments of DNA integrity, creating a clear need for advanced diagnostic tools. DNA damage can arise through pathways such as apoptosis, oxidative stress and exposure to environmental toxins, all of which compromise reproductive potential. Several methodologies exist for measuring sperm DNA fragmentation, including the sperm chromatin structure assay, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), the Comet assay and sperm chromatin dispersion, each of which has unique advantages and limitations. Novel automated imaging platforms incorporating machine learning algorithms have emerged, enabling high-throughput, single-sperm assessment and reducing subjectivity associated with manual scoring. Species differences further complicate the understanding of DNA stability and sperm quality, especially in livestock and models of artificial insemination; nonetheless, physiological similarities between humans and species close to humans provide useful translational insights. Emerging sperm selection technologies, including microfluidics, hyaluronic acid affinity systems and magnetic-activated cell sorting, show promise in reducing DNA fragmentation, improving reproductive outcomes and decreasing pregnancy loss. As the field progresses toward increasingly personalized fertility treatments, measures of DNA integrity will remain central to optimizing assisted reproduction success rates across species. In this Review, the authors synthesize current understanding of sperm DNA fragmentation and its effects on mammalian reproduction. Reproductive consequences for fertilization, embryo development, and pregnancy outcomes and strategies aimed at reducing or preventing DNA fragmentation are examined.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 9","pages":"564-591"},"PeriodicalIF":13.6,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146069980","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}

{"title":"Long-term adverse effects of modern Wilms tumour therapies: implications for monitoring","authors":"Filippo Spreafico, Giovanna Gattuso, Marta G. Podda, Olga Nigro, Valeria Colombo, Sabina Vennarini, Antonio Mastrangelo, Francesca Filippi, Giovanni Montini, Maura Massimino, Monica Terenziani","doi":"10.1038/s41585-026-01126-x","DOIUrl":"10.1038/s41585-026-01126-x","url":null,"abstract":"Wilms tumour is the most common kidney tumour in children. Owing to global collaboration and advances in clinical care, 90% of affected children, including those with metastatic disease, can now be cured. Further improvements in this outstanding outcome will depend on implementing strategies to prevent treatment-related mortality and gaining insights into the molecular and clinical drivers of Wilms tumour to introduce tailored therapies. The main treatments for Wilms tumour are nephrectomy and chemotherapy, with radiotherapy used selectively. Wilms tumour therapies can lead to long-term chronic health conditions, such as chronic kidney disease, infertility, second primary neoplasms and cardiovascular disease, despite the use of risk-adapted protocols to optimize the therapeutic index. Research into therapy de-escalation has been enhanced by survivor cohort studies investigating the chronic health conditions associated with specific Wilms tumour therapies. Understanding these relationships and which patients are most susceptible to specific toxic effects is crucial for counselling Wilms tumour survivors and their health-care providers on survivorship care planning. A classification framework could stratify survivors by their risk of treatment-related long-term morbidity, to tailor long-term follow-up monitoring and care. In this Review, the authors examine anticipated patterns of late morbidities that could emerge as a result of current treatments for Wilms tumour. Given the importance of a patient-centred follow-up strategy, they propose a practical classification system based on the likelihood of developing therapy-related late sequelae.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 8","pages":"517-532"},"PeriodicalIF":13.6,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048399","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}

{"title":"ctDNA-guided treatment decisions in muscle-invasive bladder cancer","authors":"Lars Dyrskjøt","doi":"10.1038/s41585-026-01125-y","DOIUrl":"10.1038/s41585-026-01125-y","url":null,"abstract":"The phase III IMvigor011 trial shows that postoperative circulating tumour DNA (ctDNA) can guide adjuvant immunotherapy after cystectomy, improving outcomes in patients with ctDNA-positive tumours while identifying patients with excellent prognosis without treatment. In an era of intensified perioperative therapy, these findings might shift the focus from whom to treat towards when treatment can be safely withheld or stopped.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 8","pages":"497-498"},"PeriodicalIF":13.6,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021293","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}

{"title":"Circulating tumour cells as a window into lethality in prostate cancer","authors":"Sophia M. Abusamra, Thineskrishna Anbarasan, Daniele T. Cotton, Nithesh M. S. Ranasinha, Robert Barber, Suzannah Bridge, Carolyn Smith, Sandy Figiel, Wencheng Yin, Jason J. Davis, Simpa S. Salami, Freddie C. Hamdy, Richard J. Bryant, Yong-Jie Lu, Ian G. Mills, Claire M. Edwards, Todd M. Morgan, Alastair D. Lamb","doi":"10.1038/s41585-025-01121-8","DOIUrl":"10.1038/s41585-025-01121-8","url":null,"abstract":"Prostate cancer is characterized by multifocality, inter- and intra-patient tumour heterogeneity, and differences in risk of progression to metastatic disease, castration resistance and lethality, which can make prognosis challenging. Consequently, sampling methods that provide accurate insight into disease phenotype to facilitate risk-stratification of patients are crucial. The variable biology of prostate cancer seems to be recapitulated in the phenotypic heterogeneity of circulating tumour cells (CTCs). CTC sampling offers a liquid biopsy method to achieve minimally invasive longitudinal sampling for disease monitoring. CTC analysis has also offered a crucial insight into aggressive phenotypes, disease metastasis and treatment response, particularly in clinical trials. The clinical use of CTC count for prognosis in advanced prostate cancer has been approved by the FDA, but is not routinely used clinically, as these cells are technically challenging to isolate and analyse. However, methodological advances continue to improve CTC enrichment and profiling. Understanding the clinical utility of CTCs and future innovations is crucial to incorporating CTCs into the clinical management of prostate cancer. Circulating tumour cells (CTCs) offer a minimally invasive biopsy strategy for prostate cancer monitoring. This Review discusses the use of CTCs at all stages of prostate cancer development and treatment, from CTC isolation and enrichment strategies to the prognostic and clinical utility of these cells in prostate cancer.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 8","pages":"499-516"},"PeriodicalIF":13.6,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986569","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}