Andrology最新文献

{"title":"Unveiling SMAD family member 6 as a novel biomarker for prognosis and immunotherapy response in testicular germ cell tumors.","authors":"Huawei Lin, Xiaowen Lin, Peisheng Huang, Xiaoxue Yu, Jianming Liu, Liangliang Huang, Yanni Wei, Jiahong Chen, Zhouda Cai, Le Zhang, Junhong Deng, Zhuoyuan Lin, Yu Zheng, Jianming Lu","doi":"10.1111/andr.70015","DOIUrl":"https://doi.org/10.1111/andr.70015","url":null,"abstract":"<p><strong>Background and objectives: </strong>Despite its rarity, testicular germ cell tumor (TGCT) is commonly diagnosed in young males aged 20-40. In recent years, the global prevalence of TGCT has gradually increased, with 12-30% of patients experiencing relapse and metastasis. However, there are currently no reliable biomarkers for accurately predicting the prognosis of TGCT patients. Therefore, identifying novel biomarkers for risk stratification in TGCT is an immediate priority.</p><p><strong>Materials and methods: </strong>Using TGCT samples from multiple centers, we identified a novel prognostic biomarker (SMAD family member 6 [SMAD6]) through differential expression analysis, Cox regression, and survival analysis. Immunohistochemistry (IHC) was then employed to evaluate SMAD6 expression levels in normal testicular tissues and TGCT samples. Finally, we examined the relationship between SMAD6 and its biological characteristics, mutation landscape, immune cell infiltration, and response to immunotherapy.</p><p><strong>Results: </strong>Our study identified SMAD6 as a risk factor for TGCT prognosis. IHC revealed significant expression of SMAD6 in TGCT tissues. Functional enrichment analysis indicated that SMAD6 may contribute to the activation of tumor progression-related pathways and suppression of immune-related pathways. Additionally, high SMAD6 expression was correlated with reduced CD8⁺ T cell infiltration, while patients with low SMAD6 expression benefited more from immunotherapy.</p><p><strong>Discussion and conclusions: </strong>This study highlights the potential of SMAD6 may be useful for TGCT prognosis and immunotherapy response prediction, offering a promising target for personalized medicine strategies.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490520","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":"Opioid-induced androgen deficiency in men: Prevalence, pathophysiology, and efficacy of testosterone therapy.","authors":"Hussein Kafel, Milena Braga-Basaria, Shehzad Basaria","doi":"10.1111/andr.70013","DOIUrl":"https://doi.org/10.1111/andr.70013","url":null,"abstract":"<p><strong>Background: </strong>Opioid analgesics are frequently prescribed for the treatment of chronic pain and are a common cause of male androgen deficiency. Despite its high prevalence, this adverse effect of chronic opioid use remains underappreciated by clinicians. As a result, androgen deficiency remains underdiagnosed and likely undertreated. This focused review discusses the expanding literature on opioid-induced androgen deficiency and the efficacy of testosterone therapy, with a particular focus on its anti-nociceptive effects.</p><p><strong>Methods: </strong>Original and review articles on opioid-induced male androgen deficiency published from 1950 through June 2024 were retrieved from PubMed using the key terms \"opioids,\" \"hypogonadism,\" \"low testosterone,\" and \"testosterone therapy.\" References within the retrieved publications were also researched.</p><p><strong>Results: </strong>Opioids suppress the gonadal axis mainly by inhibiting GnRH synthesis and secretion. The prevalence of opioid-induced androgen deficiency in men varies between 20% and 80% and is influenced by the type of opioid used, duration of exposure, age of the cohort, and how low testosterone was defined. Limited data from clinical trials suggest that testosterone therapy improves libido, body composition, and certain domains of quality of life. Early evidence also suggests that testosterone has anti-nociceptive properties, confirming findings from preclinical and population studies.</p><p><strong>Conclusion: </strong>Chronic opioid use is a common but underappreciated cause of androgen deficiency in men. There is a need to raise awareness among clinicians regarding this adverse effect of opioid use. Testosterone therapy could be considered in men with unequivocal androgen deficiency after a thorough clinical evaluation. Ongoing clinical trials will shed further light on the efficacy of testosterone therapy, particularly regarding its anti-nociceptive effects.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466794","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":"Loss of lncRNAs 1700101O22Rik and 1700027A15Rik causes sperm malformation and subfertility.","authors":"Shijue Dong, Ziyi Cai, Jingyan Yu, Min Liang, Yang Zhou, Mengqian Ding, Xuhui Zeng, Xiaoning Zhang","doi":"10.1111/andr.70011","DOIUrl":"https://doi.org/10.1111/andr.70011","url":null,"abstract":"<p><strong>Background: </strong>The testis is a key reservoir of long non-coding RNAs, yet their physiological roles in male reproduction remain debated. Notably, long non-coding RNAs 1700101O22Rik (22Rik) and 1700027A15Rik (15Rik) are uniquely expressed in the mouse testis. Previous research indicates that both 22Rik and 15Rik play roles in male reproductive processes; however, it is still unclear whether their effects on fertility are cumulative or compensatory.</p><p><strong>Objectives: </strong>To investigate the influence of simultaneous deletion of 22Rik and 15Rik on male reproduction and whether there are additive effects.</p><p><strong>Materials and methods: </strong>22Rik and 15Rik knockout mice were generated using CRISPR-Cas9, and double knockout mice were obtained through co-caging. To investigate reproductive phenotypes, we utilized computer-aided sperm analysis, acrosome reaction assessments, in vitro fertilization techniques, and sperm morphology analysis. Additionally, RNA sequencing and RNA binding protein immunoprecipitation were employed to explore the regulatory mechanisms of 22Rik and 15Rik.</p><p><strong>Results: </strong>The simultaneous deletion of 22Rik and 15Rik led to abnormal sperm morphology, impaired acrosome reaction, and reduced in vitro fertilization. Sperm count and fertility were also decreased in double knockout male mice. Compared to the knockout of long non-coding RNA 22Rik, reproductive abnormalities were somewhat exacerbated but largely similar to those observed with 15Rik knockout alone because of shared targeted genes, particularly Y chromosome-linked genes. Additionally, these abnormal phenotypes may be linked to reduced expression of transition protein 1 and dysfunction of the HSF2‒Rik22‒Rik15 complex in double knockout mice.</p><p><strong>Discussion and conclusion: </strong>Our study demonstrates for the first time that simultaneous knockout of these two long non-coding RNAs adversely affects sperm morphology and function by disrupting the HSF2‒Rik22‒Rik15 complex. Moreover, many overlapping regulated genes suggest that 22Rik and 15Rik may share similar regulatory mechanisms at the molecular level. This research sheds light on the causes and mechanisms behind sperm malformation and impaired male fertility.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412986","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":"First application of three-dimensional light sheet fluorescence microscopy to human testicular tumors: New perspectives in histopathology.","authors":"Diana Pinkert-Leetsch, Ahmad Kareem, Simon F Merz, Marc Teckentrup, Alexander Fichtner, Felix Bremmer, Jeannine Missbach-Guentner","doi":"10.1111/andr.70009","DOIUrl":"https://doi.org/10.1111/andr.70009","url":null,"abstract":"<p><strong>Background: </strong>Testicular tumors are among the most frequently diagnosed cancers in young men. The consequences of this diagnosis are orchiectomies, severely restricting fertility. For these young patients, a comprehensive diagnostics would be desirable, achieving a refined diagnosis and improved therapeutic patient stratification.</p><p><strong>Objective: </strong>The aim of this study was to use three-dimensional (3D) light sheet fluorescence microscopy (LSFM) to analyze a complete testicular tumor punch at subcellular resolution-allowing a detailed diagnostic assessment of the entire punch.</p><p><strong>Materials and methods: </strong>Tissue punches (3  and 5 mm diameter) were taken from paraffin blocks of four miscellaneous testicular tumors. After deparaffinization and clearing using benzoic acid/benzyl benzoate, a label-free LSFM autofluorescence imaging was performed. In addition, TO-PRO-3 nuclear stain was applied to several punches. After the scan, the samples were embedded in paraffin again and physically sectioned for conventional planar histology.</p><p><strong>Results: </strong>Based on the specific autofluorescence, not only the general morphology of the tumor tissue was identified in LSFM datasets, but also diagnostic features like infiltrations, papillary and pagetoid tumor cell formations, germ cell neoplasia in situ and azoospermia. Subcellular characteristics such as vacuolated cytoplasm and pleomorphic nuclei could be detected at maximum magnification. After nuclear staining, virtual H&E sections were reconstructed from the LSFM data and tomographically visualized across the entire punch. Subsequent histology and immunohistochemistry after LSFM analyses is possible.</p><p><strong>Discussion: </strong>LSFM analysis of testicular tumors enables the detailed 2D/3D analysis of an entire tumor punch for assessment of relevant tumor characteristics due to its intrinsic fluorescence or with specific nuclear staining.</p><p><strong>Conclusion: </strong>LSFM provides the technical basis for the analyses of complete testicular tumor biopsies, thus maximizing the spatial morphological and anatomical information. The subcellular 3D imaging of the tumor has the potential to identify new cancer imaging biomarkers that have additional diagnostic and prognostic value for patients.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397982","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":"Comprehensive diagnostic and therapeutic approach to male factor infertility aimed at natural fertility: A multicentric retrospective cohort study.","authors":"Giuseppe Grande, Andrea Garolla, Andrea Graziani, Anna Laura Astorri, Maria Vittoria Cammarota, Annamaria Merola, Maria Pia Polidori, Emanuela Lulli, Enrico Busato, Francesco Pesce, Giuseppina Pompa, Alfredo Pontecorvi, Domenico Milardi, Alberto Ferlin","doi":"10.1111/andr.70006","DOIUrl":"https://doi.org/10.1111/andr.70006","url":null,"abstract":"<p><strong>Background: </strong>In infertile couples whose male partner has alterations in semen parameters frequently, a comprehensive andrological approach is lacking and approximately 30-50% are classified as idiopathic infertility. These couples are often directly addressed to assisted reproduction techniques (ARTs). However, several clinical conditions may benefit from medical treatment. By acting on etiology and/or risk factors, this aims at improving seminal parameters and restoring natural fertility.</p><p><strong>Objectives: </strong>To verify the impact of a comprehensive andrological assessment on the management of infertility (in particular, in couples with isolated male factor infertility) using as the primary outcome the natural pregnancy rate.</p><p><strong>Materials and methods: </strong>A multicenter retrospective study was conducted between 2015 and 2022 in 1014 couples with primary infertility seeking natural conception (including 266 couples with previous ART failure). Each couple underwent a multidisciplinary evaluation. This involved: a gynecologist and an andrologist both with expertise in infertility, a psychologist when requested, and a fertility awareness practitioner according to a unique diagnostic and therapeutic multidisciplinary protocol.</p><p><strong>Results: </strong>An isolated male factor was found in 23% of couples. In 45%, it was associated with female factors also. The comprehensive diagnostic approach reduced the proportion of idiopathic infertility to 8% of the couples. Targeted treatment, based on diagnostic categories, was associated with spontaneous pregnancy in 40.9% of the couples. In the 233 cases without female factors, normal semen parameters were observed only in 13% of patients. Male genital tract inflammation was observed in 48.8% of the patients, genital tract infection in 43.1%, and hypospermatogenesis in 16.7%. Patients with infections were treated with antibiotics and probiotics. If further inflammation was documented, this was followed by low-dose corticosteroids and antioxidants. Follicle stimulating hormone (FSH) treatment was used in patients with hypospermatogenesis, and varicocele repair surgery was performed in four patients.</p><p><strong>Discussion and conclusions: </strong>Our data underline the efficacy of a comprehensive approach to the diagnostic process of male factor infertility, both in reducing the percentage of idiopathic infertility and in restoring natural fertility based on a targeted treatment.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389737","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 association of hypertension and antihypertensive medications on semen parameters among men presenting for fertility evaluation.","authors":"Daniel R Greenberg, Luis C Gago, Sai Kaushik S R Kumar, Evan J Panken, Kian Asanad, Zequn Sun, Robert E Brannigan, Joshua A Halpern","doi":"10.1111/andr.70010","DOIUrl":"https://doi.org/10.1111/andr.70010","url":null,"abstract":"<p><strong>Background: </strong>Hypertension is a common medical condition and its prevalence increases with age. Therefore, more prospective fathers will present for fertility evaluation with this diagnosis.</p><p><strong>Objective: </strong>To determine if hypertension and antihypertensive medication use are associated with impaired semen parameters.</p><p><strong>Methods: </strong>We retrospectively reviewed men with and without hypertension at the time of their index semen analysis (SA) between 2002 and 2023. Demographics, medical comorbidities, and semen parameters were evaluated between cohorts. Univariable and multivariable regression analyses were also used to determine the association of hypertension, and number and class of antihypertensive medications, and abnormal total motile sperm count (TMSC < 20 million).</p><p><strong>Results: </strong>Among 14,009 men, 10.1% (n = 1410) had a diagnosis of hypertension. Hypertensive men had significantly lower ejaculate volume (2.8 mL [interquartile range {IQR} 1.8-3.8] vs. 2.9 mL [IQR 2.0-4.0], p < 0.001) and sperm motility (58% [IQR 50-66] vs. 60% [52-68], p < 0.001). Hypertension was also independently associated with abnormal TMSC (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.05-1.40, p = 0.008) on multivariable analysis. Among patients with hypertension, men with an active antihypertensive medication prescription at the time of index SA were older and had lower sperm motility (57% [IQR 47-64] vs. 59% [IQR 52-67], p = 0.006), sperm morphology (5% [IQR 2-7] vs. 6% [3-12], p < 0.001) and TMSC (48.9 M  [IQR 16.1-94.9] vs. 68.4 M  [25.0-124.9], p < 0.001) compared to patients with no prior antihypertensive medication exposure. Multivariable analysis demonstrated no significant increased risk of abnormal TMSC between unexposed patients and those taking an antihypertensive medication.</p><p><strong>Discussion: </strong>More than one in 10 men presenting for initial fertility evaluation had a diagnosis of hypertension. This diagnosis, as well as antihypertensive medication exposure, were associated with impaired semen parameters.</p><p><strong>Conclusion: </strong>Patients interested in future fertility should be counseled regarding lifestyle modifications to appropriately treat hypertension. Further studies are required to determine the impact of antihypertensive medications and adequate control of hypertension on semen quality.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254242","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 use of deidentified organ donor testes for research.","authors":"Marina V Pryzhkova, Marnie W Skinner, Juliana I Candelaria, Stephen R Wellard, Philip W Jordan","doi":"10.1111/andr.70008","DOIUrl":"https://doi.org/10.1111/andr.70008","url":null,"abstract":"<p><p>Our knowledge of testis development and function mainly comes from research using mammalian model organisms, primarily the mouse. However, there are integral differences between men and other mammalian species regarding cellular composition and expression profiles during fetal and post-natal testis development and in the mature testis. Therefore, to specifically learn more about human testis development and function, there is a need to use human testis tissue for research. Human testicular tissues that have been donated for research have allowed extensive molecular and cytological assessments, as well as single-cell transcriptome and epigenome analyses. These tissues have also been used for the development of cell technologies and in vitro models that aim to improve infertility treatments and diagnostics. Biopsied material taken from patients and designated for research is usually very small in size and is unsuitable for comprehensive studies. On the other hand, research using whole testes obtained from deceased, deidentified donors has become a valuable resource to assess conservation between humans and other organisms and identify human-specific phenomena. This review discusses the acquisition of donated deidentified human testes and their use for basic science research.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254195","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":"Human chorionic gonadotropin-based clinical treatments for infertile men with non-obstructive azoospermia.","authors":"Sandro C Esteves, Marina C Viana, Arnold P P Achermann, Daniele Santi","doi":"10.1111/andr.70003","DOIUrl":"https://doi.org/10.1111/andr.70003","url":null,"abstract":"<p><p>Spermatogenesis is primarily controlled by follicle-stimulating hormone and luteinizing hormone-driven testosterone. Luteinizing hormone acts on the Leydig cells, stimulating steroid production, predominantly testosterone, and activating critical inter-related spermatogenesis regulatory pathways. Despite evidence that exogenous gonadotropins containing luteinizing hormone activity, particularly human chorionic gonadotropin, can effectively restore spermatogenesis in azoospermic males with hypogonadotropic hypogonadism, the use of these drugs to treat other forms of non-obstructive azoospermia is the subject of an ongoing debate. In this review, we delve into the molecular properties and functions of human chorionic gonadotropin in spermatogenesis regulation and explore available preparations for therapeutic use. We examine the evidence regarding the effectiveness of human chorionic gonadotropin in treating infertility in men with pre-testicular or testicular non-obstructive azoospermia and, additionally, identify the main areas for future research. Our review highlights the critical role of luteinizing hormone activity in spermatogenesis and emphasizes the potential of human chorionic gonadotropin in treating male infertility. The variation in the characteristics of patients with non-obstructive azoospermia underscores the importance of assessing hormonal profiles when contemplating hormonal treatment for these patients. A novel stratification of male infertility patients, the APHRODITE criteria, which considers clinical and laboratory indicators, may assist in identifying individuals who could benefit from human chorionic gonadotropin therapy. While accumulating evidence suggests promising venues for pharmacological treatment in male infertility, including non-obstructive azoospermia, further research is required to completely elucidate the mechanisms underlying the effects of exogenous gonadotropins with luteinizing hormone activity on sperm production and to establish the most effective dosages and treatment durations.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121716","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":"Motile cilia: Key developmental and functional roles in reproductive systems.","authors":"Shiyu Yang, Xiaoli Wang, Huihui Gao, Shuiqiao Yuan","doi":"10.1111/andr.70007","DOIUrl":"https://doi.org/10.1111/andr.70007","url":null,"abstract":"<p><strong>Background: </strong>Cilia are specialized microtubule-based organelles that extend from the cell surface and are classified into non-motile and motile types. The assembly and function of cilia are regulated by a complex molecular network that enables motile cilia to generate fluid flow across epithelial surfaces through coordinated beating. These motile cilia are found in the respiratory, nervous, and reproductive systems. In males, motile cilia are found in the efferent ducts and facilitate the transport of sperm from the testis to the epididymis. In females, they are mainly found in the oviducts, where they help to transport, nourish and fertilize eggs, and are also present in the endometrial epithelium.</p><p><strong>Material-methods: </strong>This review compares the common factors that affect motile cilia in both male and female reproductive tracts, discusses the origin and development of multiciliated cell and cilia within the efferent ducts and oviducts, and enumerates the infertility or related reproductive diseases that may arise due to motile cilia defects.</p><p><strong>Results-discussion: </strong>In males, motile cilia in the efferent ducts create turbulence through their beating, which keeps semen suspended and prevents ductal obstruction. In females, motile cilia are distributed on the epithelia of the oviducts and the endometrium. Specifically, motile cilia in the infundibulum of the oviduct aid in capturing oocytes, while cilia in the isthmus region have been found to bind to sperm heads, facilitating the formation of the sperm reservoir. Several common factors, such as miR-34b/c and miR-449, TAp73, Gemc1, and estrogen, etc., have been shown to play crucial regulatory roles in motile cilia within the efferent ducts and oviducts, thereby further influencing fertility outcomes.</p><p><strong>Conclusions: </strong>Pathogenic mutations that disrupt ciliary function can impair ciliogenesis or alter the structure of sperm flagella, potentially resulting in infertility. Consequently, motile cilia in both the male and female reproductive tracts are crucial for fertility. There are still numerous unresolved mysteries surrounding these cilia that merit further investigation by researchers, as they hold great significance for the clinical diagnosis and treatment of infertility and related reproductive disorders.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078461","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":"Role of Kctd13 in modulating AR and SOX9 expression in different penile cell populations.","authors":"Carolina J Jorgez, Ahmed Chahdi, Hunter Flores, Marisol O'Neill, Abhishek Seth","doi":"10.1111/andr.70005","DOIUrl":"10.1111/andr.70005","url":null,"abstract":"<p><strong>Objective: </strong>Micropenis is a condition with significant physical and psychological implications caused mainly by decreased androgen action in penile development. Kctd13-knockout (Kctd13-KO) mice have micropenis, cryptorchidism, and fertility defects because of reduced levels of androgen receptor (AR) and SOX9. We hypothesized that normalizing the levels of AR and SOX9 in the Kctd13-KO penis could help us to understand the mechanism of action of these signaling pathways on penile development.</p><p><strong>Methods: </strong>We generated transgenic mice lacking Kctd13 and conditionally expressing AR in the urethral mesenchyme after Cre activation with Twist2^cre (Kctd13-KO; AR-CMV; Twist2^cre; herein called AR+), and Sox9 in the urethral epithelium after Cre activation with Shh^cre (Kctd13-KO; Sox9-CAG; Shh^cre; herein called SOX9+). Mice penile morphology, fertility, and the effect of KCTD13 on AR and SOX9 ubiquitination were evaluated.</p><p><strong>Results and discussion: </strong>Kctd13-KO micropenis phenotype was rescued after increasing levels of penile AR or SOX9 as transgenic AR+ and SOX9+ mice have longer penile lengths than Kctd13-KO mice and are comparable to WT mice. In addition, male-urogenital-mating-protuberance and the baculum were significantly shorter and narrower in Kctd13-KO mice compared with transgenic AR+ and SOX9+ mice. The position of the urethral meatus was similar and orthotopic in location in Kctd13-KO, AR+, SOX9+, and WT penises indicating that none of these mice had hypospadias. The subfertility of AR+ and SOX9+ mice was improved. The ectopic expression of KCTD13 in HEK293 cells strongly reduced AR ubiquitination which is abolished when the proteasome pathway is inhibited and this process is mediated by the ubiquitin ligase, STUB1. The effect of KCTD13 on SOX9 ubiquitination is minimal.</p><p><strong>Conclusion: </strong>KCTD13 regulates AR ubiquitination by modulating STUB1 binding to AR. Penile restoration of AR and SOX9 improved penile development in Kctd13-KO mice allowing us to discern the contribution from individual signaling pathways and cell types in penile development.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063371","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}