Andrology最新文献

{"title":"Oligoasthenoteratozoospermic patients with high untreatable sperm DNA fragmentation and prior ICSI failure using ejaculated sperm have signs of partial epididymal obstruction.","authors":"Ettore Caroppo, Fabrizio Castiglioni, Kelly Cabrilo, Marina Bellavia, Giacomo Gazzano, Giovanni M Colpi","doi":"10.1111/andr.70044","DOIUrl":"https://doi.org/10.1111/andr.70044","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have suggested using testicular sperm for ICSI in patients with oligoasthenoteratozoospermia (OAT) and high, untreatable sperm DNA fragmentation (SDF) with prior ICSI failures using ejaculated sperm, to improve their chances of successful ICSI outcome.</p><p><strong>Objectives: </strong>To assess whether such patients have signs of partial epididymal obstruction.</p><p><strong>Materials and methods: </strong>We retrospectively evaluated 72 infertile men with OAT (sperm count < 10 million/mL, progressive motility < 30%, morphology < 4%) and high (> 30%) SDF who underwent ICSI with testicular sperm following at least two prior ICSI failures with ejaculated sperm; they were divided in two subgroups based on testis histology results indicating either normal or impaired spermatogenesis. 186 patients with nonobstructive azoospermia (NOA) and 45 patients with obstructive azoospermia (OA) served as control subjects for hormonal and histological parameters.</p><p><strong>Results: </strong>34 out of 72 (47.2%) OAT patients had normal spermatogenesis, with hormonal and histopathological characteristics comparable to those of men with OA, while 38 patients (52.7%) showed spermatogenic dysfunction but of lesser severity compared to patients with NOA. At scrotal surgical inspection, all OAT patients showed signs of partial epididymal obstruction. ICSI clinical pregnancy and live birth rate using testicular sperm was 45.8% and 36.11% respectively, and did not differ among patients with normal or impaired spermatogenesis (50% vs. 42%, p = 0.64, and 41.1% vs. 31.5%, p = 0.47, respectively).</p><p><strong>Discussion: </strong>We hypothesize that partial epididymal obstruction may affect sperm maturation, particularly in relation to the noncoding RNA payload required for fertilization and early embryo development, which is acquired during epididymal transit. Nucleases activation in the cauda epididymis and vas deferens may degrade sperm DNA to prevent the involvement of functionally altered sperm in oocyte fertilization.</p><p><strong>Conclusion: </strong>High untreatable SDF, together with prior ICSI failure using ejaculated sperm, could be interpreted as sign of partial epididymal obstruction in patients with OAT.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Embryological, clinical, and newborn outcomes from 583 treatment cycles with fresh and frozen testicular spermatozoa.","authors":"Mariana Pereira, Mariana Cunha, Joaquina Silva, Paulo Viana, Nuno Barros, José Teixeira da Silva, Cristiano Oliveira, Luís Ferraz, Alberto Barros, Mário Sousa","doi":"10.1111/andr.70041","DOIUrl":"https://doi.org/10.1111/andr.70041","url":null,"abstract":"<p><strong>Background: </strong>Besides non-obstructive azoospermia, other conditions also benefit from the use of testicular sperm extraction, but their clinical outcomes remain to be explored in detail.</p><p><strong>Objective: </strong>To compare the use of fresh and frozen testicular spermatozoa in patients submitted to testicular sperm extraction because of idiopathic or secondary non-obstructive azoospermia, and after recurrent failed intracytoplasmic sperm injection attempts using ejaculated or aspirated testicular spermatozoa.</p><p><strong>Materials and methods: </strong>We retrospectively evaluated 325 patients with normal karyotypes and absence of Y-chromosome microdeletions that used testicular sperm extraction for fertility treatments. Comparisons included detailed embryological, clinical, and newborn outcomes.</p><p><strong>Results: </strong>Patients underwent 503 treatment cycles, 269 with fresh and 234 with frozen testicular spermatozoa. No significant differences were observed between fresh and frozen spermatozoa regarding clinical pregnancy (38.0%/43.2%), live birth delivery (32.2%/34.0%), and newborn (40.1%/43.2%) rates, the same being observed in cumulative clinical pregnancy (47.9%/48.5%), live birth delivery (41.7%/38.3%), and newborn (50.4%/48.5%) rates. Also, no significant differences were observed between fresh and frozen spermatozoa per pathology (idiopathic or secondary non-obstructive azoospermia, cryptorchidism, abnormal semen parameters, cryptozoospermia, obstructive azoospermia, and anejaculation). However, in idiopathic non-obstructive azoospermia, frozen embryo transfer cycles from fresh sperm cycles evidenced significantly higher rates of live birth delivery and newborn. As cycles with frozen spermatozoa evidenced significantly higher female age, time of infertility, and basal follicle stimulating hormone, and significantly lower number of follicles, female characteristics were thereafter individualized. The presence of mixed factors did not affect outcomes. Good ovarian response cases exhibited significantly higher rates of implantation and newborn, whereas younger women cases showed significantly higher rates of implantation, clinical pregnancy, and newborn; however, when fresh spermatozoa were compared to frozen spermatozoa, these differences were no longer present.</p><p><strong>Discussion and conclusion: </strong>Data provide detailed embryological, clinical, and newborn outcomes associated with specific conditions in which testicular sperm extraction was required. It also highlights no detrimental effects on outcomes when frozen testicular spermatozoa is used.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fetal exposure to a mixture of endocrine-disrupting chemicals and biomarkers of male fecundity: A population-based cohort study.","authors":"Sidsel Dan Hull, Karin Sørig Hougaard, Gunnar Toft, Kajsa Kirstine Ugelvig Petersen, Esben Meulengracht Flachs, Christian Lindh, Cecilia Høst Ramlau-Hansen, Lauren A Wise, Allen Wilcox, Zeyan Liew, Jens Peter Bonde, Sandra Søgaard Tøttenborg","doi":"10.1111/andr.70039","DOIUrl":"https://doi.org/10.1111/andr.70039","url":null,"abstract":"<p><strong>Background: </strong>Fetal exposure to endocrine-disrupting chemicals (EDCs) has been associated with reduced male fecundity, but with few studies considering chemical mixtures.</p><p><strong>Objectives: </strong>We assessed the association between fetal exposure to a mixture of EDCs and biomarkers of male fecundity in young adulthood.</p><p><strong>Materials and methods: </strong>The study population comprised 841 young adult males enrolled in the Fetal Programming of Semen Quality cohort, established as a male offspring sub-cohort within the Danish National Birth Cohort. Maternal blood samples were analyzed for concentrations of per- and polyfluoroalkyl substances (PFAS), phthalate metabolites, and triclosan. We used quantile g-computation to estimate the change in semen characteristics, testicular volume, and reproductive hormone levels with 95% confidence intervals (CI) per one-quartile increase in all chemicals within three chemical mixtures; an overall chemical mixture, a PFAS mixture, and a non-persistent chemical mixture.</p><p><strong>Results: </strong>Fetal exposure to a one-quartile increase in the overall chemical mixture was associated with 4.0 million/mL lower sperm concentration (95% CI: -9.1, 1.1), 16.1 million lower total sperm count (95% CI: -33.8, 1.6), 0.5 mL smaller testicular volume (95% CI: -1.2, 0.3), 5% higher proportion of non-progressive and immotile spermatozoa (95% CI: 0.99, 1.11), and 7% higher concentration of FSH (95% CI: 0.99, 1.16), but with limited precision. Effect sizes were greatest in magnitude for sperm concentration and total sperm count. We observed somewhat similar associations for the PFAS mixture and no associations for the non-persistent chemical mixture.</p><p><strong>Discussion: </strong>Results suggest that fetal exposure to an overall mixture of EDCs may be adversely associated with several biomarkers of male fecundity, but findings are also compatible with null associations. These associations, if true, appeared to be driven by PFAS, but misclassification due to a single measurement of the phthalate metabolites and triclosan may have attenuated the results.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applications of spatial transcriptomics in studying spermatogenesis","authors":"Qianlan Xu,&nbsp;Haiqi Chen","doi":"10.1111/andr.70043","DOIUrl":"10.1111/andr.70043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Spermatogenesis is a complex differentiation process that is facilitated by a series of cellular and molecular events. High-throughput genomics approaches, such as single-cell RNA sequencing, have begun to enable the systematic characterization of these events. However, the loss of tissue context because of tissue disassociations in the single-cell isolation protocols limits our ability to understand the regulation of spermatogenesis and how defects in spermatogenesis lead to infertility. The recent advancement of spatial transcriptomics technologies enables the studying of the molecular signatures of various cell types and their interactions in the native tissue context. In this review, we discuss how spatial transcriptomics has been leveraged to identify spatially variable genes, characterize cellular neighborhood, delineate cell‒cell communications, and detect molecular changes under pathological conditions in the mammalian testis. We believe that spatial transcriptomics, along with other emerging spatially resolved omics assays, can be utilized to further our understanding of the underlying causes of male infertility, and to facilitate the development of new treatment approaches.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"13 5","pages":"1181-1189"},"PeriodicalIF":3.2,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/andr.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between systemic immune inflammation index and serum testosterone and free testosterone in middle-aged and elderly men.","authors":"Liang Su, Si-Zheng Zhang, Hao-Yang Cheng, Zheng-Yang Zhou, Qi Zhang, Jie Wu, Yong-Zheng Jiao","doi":"10.1111/andr.70036","DOIUrl":"https://doi.org/10.1111/andr.70036","url":null,"abstract":"<p><strong>Background: </strong>Chronic inflammation is a pervasive feature of aging and may be associated with testosterone in middle-aged and older men. Systemic immune-inflammation index (SII) is a novel inflammatory biomarker. We aimed to assess the association between SII and serum testosterone and free testosterone (FT) in middle-aged and older men.</p><p><strong>Methods: </strong>Our study included males ≥ 40 years old in the 2011-2016 and 2021-2023 National Health and Nutrition Examination Survey. Multivariable regression analysis was used to explore the associations between SII and serum testosterone and FT in middle-aged and older men. Subgroup analysis was performed according to age.</p><p><strong>Results: </strong>About 5354 participants were included, of which 2450 contained FT data. Multivariable linear regression found that SII exhibited an inverse association with serum testosterone (β -0.05, 95% CI -0.07 to -0.03, P < 0.001) and FT (β -0.03, 95% CI -0.05 to -0.01, P = 0.032) in middle-aged and elderly men. After SII was grouped as quartiles, serum testosterone was significantly lower in SII quartile 4 than in SII quartile 1 (β -0.05, 95% CI -0.08 to -0.02, P < 0.001). However, FT was not significantly lower in SII quartile 4 than in SII quartile 1 (β -0.03, 95% CI -0.07 to 0.01, P = 0.135). In subgroup analysis, the serum testosterone results were consistent with the overall results. However, only in the ≥60 years group, SII exhibited an inverse association with FT (β -0.06, 95% CI -0.1 to -0.02, P = 0.002) and was significantly lower in SII quartile 4 than in SII quartile 1 (β -0.06, 95% CI -0.12 to -0.01, P = 0.049).</p><p><strong>Conclusions: </strong>Our study revealed an inverse association between SII and serum testosterone and FT in middle-aged and elderly men, particularly among men ≥ 60 years.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Standardized outcome measures for reporting results from male contraceptive efficacy trials.","authors":"John K Amory","doi":"10.1111/andr.70042","DOIUrl":"https://doi.org/10.1111/andr.70042","url":null,"abstract":"<p><strong>Background: </strong>Standardized methodology for reporting outcomes for male contraceptive trials has not been published. For male contraceptive studies that suppress spermatogenesis, contraceptive failures can occur during the sperm suppression phase or by sperm rebound or due to an unintended pregnancy during the efficacy phase. These three types of contraceptive failure differ from female contraceptives studies and necessitate a novel approach to reporting results from male contraceptive efficacy trials.</p><p><strong>Methods: </strong>A standardized approach to reporting contraceptive outcomes for male contraceptive efficacy trials is proposed highlighting the three types of contraceptive failure: suppression failure, sperm rebound, and unintended pregnancy. This approach is used to retrospectively analyze published male contraceptive efficacy studies. Data on adverse events and other dropouts from these trials and data from condom use are also presented to give an overall picture of the contraceptive effectiveness of these methods.</p><p><strong>Results: </strong>In 2217 men enrolled in the five male hormonal contraceptive efficacy studies included in the analysis, the suppression failure rate was 3.3% (95% CI: 2.6-4.2). The sperm rebound rate during efficacy was 1.4% (95% CI: 0.9%-1.9%), and the unintended pregnancy rate during efficacy was 1.1% (95% CI: 0.8%-1.7%). The combined contraceptive failure rate was 6.2% (95% CI: 5.2%-7.3%). In these trials, dropouts from adverse events occurred in 3.9% (95% CI: 3.1%-4.9%) of men, while discontinuations for other reasons occurred for 20% (95% CI: 18%-22%) of men. In total, 70% (95% CI: 68%-72%) of men experienced effective contraception.</p><p><strong>Conclusions: </strong>Contraceptive failure in male contraceptive trials may be described with a three-outcome approach. Combining contraceptive failure measures with adverse event and dropout rates results in a clearer understanding of contraceptive effectiveness for the method under study.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of age at first visit on glycolipid metabolism, bone metabolism, and fertility potential in patients with Klinefelter syndrome.","authors":"Giordana Ferraioli, Andrea Graziani, Noemi Sagone, Andrea Di Nisio, Massimo Iafrate, Fabrizio Dal Moro, Alberto Ferlin, Andrea Garolla","doi":"10.1111/andr.70033","DOIUrl":"https://doi.org/10.1111/andr.70033","url":null,"abstract":"<p><strong>Background: </strong>Classic Klinefelter syndrome (KS) is characterized by one extra X chromosome (47, XXY), leading to hypergonadotropic hypogonadism and higher risk of alterations in glycolipid homeostasis, cardiovascular diseases, and low bone mineral density. Most frequently, KS is diagnosed in adulthood because of infertility.</p><p><strong>Objectives: </strong>To investigate the potential association between the age at first visit and the presence of comorbidities in patients with KS.</p><p><strong>Materials and methods: </strong>In this cross-sectional retrospective study, we analyzed the data from 445 patients affected by non-mosaic 47, XXY KS and aged less than 50 years. Anthropometric measurements, biochemical and hormonal tests, semen analysis, scrotal echo-color Doppler, and dual energy X-ray absorptiometry (DXA) were performed on the patients. A subset of patients underwent testicular sperm extraction (TESE).</p><p><strong>Results: </strong>Age at first visit significantly correlated positively with waist circumference (WC), body mass index (BMI), blood glucose, glycated hemoglobin, total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides, and negatively with total testosterone (TT), calculated free testosterone (cFT), calcium, phosphorus, vitamin D, and lumbar Z-score. Age at the first visit >26 years was associated with higher frequency of increased WC, BMI, and hypercholesterolemia. Among the 199 patients who underwent testicular biopsy, the mean retrieval rate was 36.2% and was higher in the younger group (<26 years).</p><p><strong>Discussion and conclusion: </strong>Early diagnosis and management of KS is important for preventing or reducing comorbidities later in life. In particular, glycemic, lipid, and phospho-calcium metabolism worsen with advancing age at first visit. Furthermore, early management of the patient seems to be associated with a higher probability of recovering spermatozoa through TESE.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peyronie's disease in the United States: A real-world, 13-year nationwide analysis of demographics, clinical characteristics, and treatment trends.","authors":"Angelo Orsini, Eugenio Bologna, Gabriele Bignante, Francesco Lasorsa, Luca Lambertini, Arianna Biasatti, Giovanni Liguori, Michele Marchioni, Francesco Porpiglia, Giuseppe Lucarelli, Luigi Schips, Davide Arcaniolo, Marco De Sio, Edward E Cherullo, Riccardo Autorino, Celeste Manfredi","doi":"10.1111/andr.70029","DOIUrl":"https://doi.org/10.1111/andr.70029","url":null,"abstract":"<p><strong>Background: </strong>Real-world data on Peyronie's disease remains limited.</p><p><strong>Objectives: </strong>Describe the demographics, clinical characteristics, and therapeutic management of Peyronie's disease patients in the United States.</p><p><strong>Materials and methods: </strong>A retrospective analysis was conducted using the PearlDiver Mariner database (2010-2022). Male adults with Peyronie's disease were identified using the International Classification of Diseases codes. Data included demographics, clinical conditions, and treatments. Analysis was performed using R-based software.</p><p><strong>Results: </strong>Among 176,969 patients (mean age 58.9 years), hypertension (72.9%), diabetes (40.4%), and obesity (31.1%) were the most common comorbidities. Smoking was prevalent in 41.5%. Dupuytren's contracture affected 3.1%, penile trauma 0.2%, erectile dysfunction 28.2%, and depression 19%. Most patients were from the southern US (42.9%). Social determinants of health were noted in 30.9%. Treatment was received by only 13.2%. Intraplaque injections were the most frequent therapy (7.2%) and showed an increasing trend (p = 0.014). Surgical interventions (8.1%) included plication (35.1%), grafting (13%), prosthesis implantation (36.2%), and multiple techniques (15.7%). Grafting was linked to higher de novo erectile dysfunction risk.</p><p><strong>Discussion: </strong>Hypertension, diabetes, and smoking are frequent among Peyronie's disease patients. Erectile dysfunction and depression are common within a year of diagnosis. Despite multiple treatment options, only 15% of patients receive therapy. Injections are increasingly preferred, while surgery remains underutilized. Inflatable prostheses are the favored option for prosthetic management.</p><p><strong>Conclusion: </strong>Peyronie's disease patients often have significant comorbidities. Treatment rates are low, with injections as the most used therapy. Surgical interventions are less common, with stable trends over time.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mythological and archaeological perspectives on penectomy and orchiectomy: The case of Cybele and Attis.","authors":"Coskun Kaya","doi":"10.1111/andr.70040","DOIUrl":"https://doi.org/10.1111/andr.70040","url":null,"abstract":"<p><p>Castration has been a significant theme in mythology, religious traditions, and historical practices, often symbolizing transformation, sacrifice, and divine punishment. While the term is frequently associated with orchiectomy (removal of the testes), this study argues that penectomy (removal of the penis) must also be considered, particularly in myths where the symbolic weight of castration extends beyond mere fertility loss. The myth of Cybele and Attis serves as a compelling example, raising questions about the intended nature of Attis' self-mutilation and its implications.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRD9 inhibition as potential treatment option for testicular germ cell tumors.","authors":"Aylin Hansen, Christine Sanders, Florian Fronhoffs, Kai Funke, Glen Kristiansen, Hubert Schorle","doi":"10.1111/andr.70038","DOIUrl":"https://doi.org/10.1111/andr.70038","url":null,"abstract":"<p><strong>Background: </strong>Testicular germ cell tumors (TGCT) are the predominant tumor in younger males. Usually, 5-year survival rates are quite high, but 15-20% of patients with metastatic non-seminomas are resistant to standard cisplatin-based therapy. Interfering with the epigenetic landscape has already been shown to be effective in prostate cancer. BRD9 is an epigenetic reader that is part of a chromatin-remodeling complex involved in regulation of gene expression.</p><p><strong>Objectives: </strong>Alternative treatment options for therapy-resistant TGCT patients need to be investigated.</p><p><strong>Materials and methods: </strong>BRD9 expression was analyzed by meta-analysis of microarray data as well as by Western blot and immunohistochemistry of tissue microarrays in TGCT cell lines and TGCT tissues. Viability was assessed by performing XTT-assay to determine the effect of BRD9 inhibition in TGCT cell lines. FACS analysis was used to display changes in cell cycle distribution as well as apoptosis. The impact on transcriptome level of BRD9 inhibition was analyzed by 3'mRNA-sequencing.</p><p><strong>Results: </strong>BRD9 was heterogeneously expressed in TGCT cell lines and tissues. Nevertheless, inhibition of BRD9 led to a strong decrease in viability. I-BRD9 induced apoptosis as well as cell cycle arrest in G1-phase. On transcriptome level, prominent downregulation of pluripotency markers (NANOG, PRMD14, and KLF4) and upregulation of genes involved in epithelium development were detected.</p><p><strong>Discussion: </strong>I-BRD9 treatment of TGCT cell lines reduced viability, induced apoptosis and cell cycle arrest while control cells remain only slightly affected. Transcriptomic data indicate exit of pluripotency and differentiation toward the epithelial fate. In fact, loss of pluripotency and differentiation seems to be a common aspect of germ cell tumors (GCT) reacting to drug application.</p><p><strong>Conclusion: </strong>The data implicate I-BRD9 as a possible treatment alternative for TGCTs.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750739","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}