Male Infertility is a prevalent condition worldwide, and a substantial fraction of cases are thought to have a genetic basis. Investigations into the responsible genes is limited experimentally, so mice have been used extensively to identify genes required for fertility and to understand their functions.
{"title":"Relevance, strategies, and added value of mouse models in androgenetics","authors":"Vertika Singh, John C. Schimenti","doi":"10.1111/andr.13761","DOIUrl":"https://doi.org/10.1111/andr.13761","url":null,"abstract":"Male Infertility is a prevalent condition worldwide, and a substantial fraction of cases are thought to have a genetic basis. Investigations into the responsible genes is limited experimentally, so mice have been used extensively to identify genes required for fertility and to understand their functions.","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"15 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252706","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}
Primary spermatogenic disorders represent a severe form of male infertility whereby sperm production is impaired due to testicular dysfunction, leading to reduced quality or quantity of spermatozoa. Gene-centered research has certainly demonstrated the importance of the genetic factor in the etiology of both poor sperm morphology or motility and reduced sperm count. In the last decade, next-generation sequencing has expanded the research to whole exome which has transformed our understanding of male infertility genetics, but uncertainty persists in its diagnostic yield, especially in large unrelated populations.
{"title":"Utility of exome sequencing in primary spermatogenic disorders: From research to diagnostics","authors":"Antoni Riera-Escamilla, Liina Nagirnaja","doi":"10.1111/andr.13753","DOIUrl":"https://doi.org/10.1111/andr.13753","url":null,"abstract":"Primary spermatogenic disorders represent a severe form of male infertility whereby sperm production is impaired due to testicular dysfunction, leading to reduced quality or quantity of spermatozoa. Gene-centered research has certainly demonstrated the importance of the genetic factor in the etiology of both poor sperm morphology or motility and reduced sperm count. In the last decade, next-generation sequencing has expanded the research to whole exome which has transformed our understanding of male infertility genetics, but uncertainty persists in its diagnostic yield, especially in large unrelated populations.","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"209 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252705","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}
Recent advances in single‐cell transcriptomic data have greatly expanded our understanding of both spermatogenesis and the molecular mechanisms of male infertility. However, this growing wealth of data could also shed light on a seemingly unrelated biological problem: the genetic basis of mammalian brain size expansion throughout evolution. It is now increasingly recognized that the testis and brain share many cellular and molecular similarities including pivotal roles for the RAS/MAPK and PI3K/AKT/mTOR pathways, mutations in which are known to have a pronounced impact on cell proliferation. Most notably, in the stem cell lineages of both organs, new mutations have been shown to increase cellular output over time. These include ‘selfish’ mutations in spermatogonial stem cells, which disproportionately increase the proportion of mutant sperm, and—to draw a parallel—human‐specific mutations in neural stem cells which, by increasing the number of neurons, have been implicated in neocortical expansion. Here we speculate that the origin for many ‘expansion’‐associated mutations is the male germline and that as such, a deeper understanding of the mechanisms controlling testicular turnover may yield fresh insight into the biology and evolution of the brain.
{"title":"Can the male germline offer insight into mammalian brain size expansion?","authors":"Stephen J. Bush, Anne Goriely","doi":"10.1111/andr.13766","DOIUrl":"https://doi.org/10.1111/andr.13766","url":null,"abstract":"<jats:label/>Recent advances in single‐cell transcriptomic data have greatly expanded our understanding of both spermatogenesis and the molecular mechanisms of male infertility. However, this growing wealth of data could also shed light on a seemingly unrelated biological problem: the genetic basis of mammalian brain size expansion throughout evolution. It is now increasingly recognized that the testis and brain share many cellular and molecular similarities including pivotal roles for the RAS/MAPK and PI3K/AKT/mTOR pathways, mutations in which are known to have a pronounced impact on cell proliferation. Most notably, in the stem cell lineages of both organs, new mutations have been shown to increase cellular output over time. These include ‘selfish’ mutations in spermatogonial stem cells, which disproportionately increase the proportion of mutant sperm, and—to draw a parallel—human‐specific mutations in neural stem cells which, by increasing the number of neurons, have been implicated in neocortical expansion. Here we speculate that the origin for many ‘expansion’‐associated mutations is the male germline and that as such, a deeper understanding of the mechanisms controlling testicular turnover may yield fresh insight into the biology and evolution of the brain.","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"20 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268780","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}
BackgroundFrom October 7, 2023, until August 28, 2024, 187 posthumous sperm retrieval (PSR) procedures have been conducted on deceased men, 171 of whom are soldiers. PSR was predominantly initiated by parents to cope with their profound loss. However, the attitudes of Israeli men toward this procedure are unknown.ObjectiveThis study aims to investigate the attitudes of Israeli men toward prior consent to PSR and posthumous‐assisted reproduction (PAR) initiated by partner or parents.MethodsA cross‐sectional study of 600 Israeli men aged 18–49 years who were questioned in February–April 2024 amid the ongoing armed conflict. The questionnaire included demographic details, role in the conflict, and attitudes toward PSR/PAR. Multivariable logistic regression analysis was used to assess agreement for PSR/PAR after adjustment for possible confounders.ResultsThe average age of participants was 32 years, with 52% married or in a committed relationship and 6.5% self‐identified as having same‐sex relationships. The majority were secular (63%), 21% were traditional (21%), and 16% were religious. In terms of involvement in the ongoing conflict, 35% served in combat, 21% in non‐combat roles, and 44% did not participate. Most men (71%) prefer pre‐documenting their PSR preferences, with 70% advocating for consent during recruitment for regular military service and 78% before reserve service. Regarding PAR, 37% opposed it at their partner's request, while 47% opposed it at their parents’ request. In a multivariable model, the odds of approval of PAR following parental request were four‐ and three‐fold higher among traditional and secular versus religious men (odds ratio, OR = 4.1, 95% CI: 2.0–8.1 and OR = 3.3, 95% CI: 1.8–6.2, respectively) and following the request of a partner, twice higher among traditional and secular versus religious (OR = 2.0, 95% CI: 1.1–4.2 and OR = 2.0, 95% CI: 1.1–3.6, respectively).ConclusionWhile it is understandable that grieving parents seek solace through PSR, consent should be obtained from the men themselves, as a considerable proportion do not support the process as it is currently performed.
背景从2023年10月7日到2024年8月28日，已经对187名男性死者进行了遗体取精（PSR）手术，其中171人是军人。PSR主要是由父母发起的，以应对他们的巨大损失。本研究旨在调查以色列男性对事先同意由伴侣或父母发起的 PSR 和死后辅助生殖（PAR）的态度。方法对 600 名年龄在 18-49 岁之间的以色列男性进行了横断面研究，这些男性于 2024 年 2-4 月在持续的武装冲突中接受了问卷调查。问卷内容包括人口统计学细节、在冲突中的角色以及对 PSR/PAR 的态度。结果参与者的平均年龄为 32 岁，52% 已婚或有固定关系，6.5% 自认有同性关系。大多数人是世俗的（63%），21%是传统的（21%），16%是宗教的。在参与当前冲突方面，35% 的人参加过战斗，21% 的人担任过非战斗性角色，44% 的人没有参与。大多数男性（71%）倾向于事先记录他们的 PSR 偏好，70% 的人主张在正规军招募时征得同意，78% 的人主张在预备役服役前征得同意。关于 PAR，37% 的人应伴侣的要求反对，47% 的人应父母的要求反对。在多变量模型中，应父母要求同意 PAR 的几率在传统男性和世俗男性中分别是宗教男性的四倍和三倍（几率比，OR = 4.1，95% CI：2.0-8.1 和 OR = 3.3，95% CI：1.8-6.2），应伴侣要求同意 PAR 的几率在传统男性和世俗男性中是宗教男性的两倍（OR = 2.结论虽然悲伤的父母通过 PSR 寻求慰藉是可以理解的，但应征得男性本人的同意，因为相当一部分人并不支持目前的做法。
{"title":"Israeli men's attitudes toward posthumous reproduction and prior consent amid ongoing armed conflict","authors":"Bella Savitsky, Talia Eldar‐Geva, Rachel Shvartsur","doi":"10.1111/andr.13757","DOIUrl":"https://doi.org/10.1111/andr.13757","url":null,"abstract":"BackgroundFrom October 7, 2023, until August 28, 2024, 187 posthumous sperm retrieval (PSR) procedures have been conducted on deceased men, 171 of whom are soldiers. PSR was predominantly initiated by parents to cope with their profound loss. However, the attitudes of Israeli men toward this procedure are unknown.ObjectiveThis study aims to investigate the attitudes of Israeli men toward prior consent to PSR and posthumous‐assisted reproduction (PAR) initiated by partner or parents.MethodsA cross‐sectional study of 600 Israeli men aged 18–49 years who were questioned in February–April 2024 amid the ongoing armed conflict. The questionnaire included demographic details, role in the conflict, and attitudes toward PSR/PAR. Multivariable logistic regression analysis was used to assess agreement for PSR/PAR after adjustment for possible confounders.ResultsThe average age of participants was 32 years, with 52% married or in a committed relationship and 6.5% self‐identified as having same‐sex relationships. The majority were secular (63%), 21% were traditional (21%), and 16% were religious. In terms of involvement in the ongoing conflict, 35% served in combat, 21% in non‐combat roles, and 44% did not participate. Most men (71%) prefer pre‐documenting their PSR preferences, with 70% advocating for consent during recruitment for regular military service and 78% before reserve service. Regarding PAR, 37% opposed it at their partner's request, while 47% opposed it at their parents’ request. In a multivariable model, the odds of approval of PAR following parental request were four‐ and three‐fold higher among traditional and secular versus religious men (odds ratio, OR = 4.1, 95% CI: 2.0–8.1 and OR = 3.3, 95% CI: 1.8–6.2, respectively) and following the request of a partner, twice higher among traditional and secular versus religious (OR = 2.0, 95% CI: 1.1–4.2 and OR = 2.0, 95% CI: 1.1–3.6, respectively).ConclusionWhile it is understandable that grieving parents seek solace through PSR, consent should be obtained from the men themselves, as a considerable proportion do not support the process as it is currently performed.","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"14 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252711","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}
Cem Aksoy, Sascha Wellenbrock, Philipp Reimold, Philipp Karschuck, Mahmut Ozturk, Tobias Hirsch, Michael Sohn, Nicole Eisenmenger, Sabine Kliesch, Saskia Morgenstern, Aristeidis Zacharis, Johannes Huber, Luka Flegar
PurposeTo delineate the current trends regarding gender‐affirming surgeries (GAS) in Germany.MethodsAnalysis of German hospital quality reports from 2006 to 2022 was conducted using the reimbursement.info tool. The German procedure classification (OPS) codes 5‐646.0 for masculinizing‐ and 5‐646.1 for feminizing surgery were assessed to identify GAS. Linear regression models were utilized for the analysis and depiction of current trends.ResultsA total of 19,632 gender‐affirming procedures were performed during the study period with an exponential increase over the years. Masculinizing surgeries increased from 246 in 2006 to 1291 cases in 2022 (increase by 424%; p < 0.001). The highest annual increase of 37.2% in numbers was from 2018 to 2019 (from 1235 to 1694 cases). Feminizing surgeries increased from 180 cases in 2006 to 799 procedures in 2022 (increase by 343%; p < 0.001). The cases increased most between 2015 and 2016 from 277 to 502 cases (81.2%). The number of hospitals offering these surgeries expanded from 24 in 2006 to 29 in 2022 (21% increase; p < 0.001).ConclusionThis study demonstrates an exponential growth in numbers feminizing and masculinizing of GAS performed each year in Germany. Furthermore, a discernible trend emerges with a propensity for concentration of procedures within selected high‐caseload centers across Germany.
{"title":"Genital gender‐affirming surgery trends in Germany: Total population data with 19,600 cases from 2006 to 2022","authors":"Cem Aksoy, Sascha Wellenbrock, Philipp Reimold, Philipp Karschuck, Mahmut Ozturk, Tobias Hirsch, Michael Sohn, Nicole Eisenmenger, Sabine Kliesch, Saskia Morgenstern, Aristeidis Zacharis, Johannes Huber, Luka Flegar","doi":"10.1111/andr.13762","DOIUrl":"https://doi.org/10.1111/andr.13762","url":null,"abstract":"PurposeTo delineate the current trends regarding gender‐affirming surgeries (GAS) in Germany.MethodsAnalysis of German hospital quality reports from 2006 to 2022 was conducted using the reimbursement.info tool. The German procedure classification (OPS) codes 5‐646.0 for masculinizing‐ and 5‐646.1 for feminizing surgery were assessed to identify GAS. Linear regression models were utilized for the analysis and depiction of current trends.ResultsA total of 19,632 gender‐affirming procedures were performed during the study period with an exponential increase over the years. Masculinizing surgeries increased from 246 in 2006 to 1291 cases in 2022 (increase by 424%; <jats:italic>p</jats:italic> < 0.001). The highest annual increase of 37.2% in numbers was from 2018 to 2019 (from 1235 to 1694 cases). Feminizing surgeries increased from 180 cases in 2006 to 799 procedures in 2022 (increase by 343%; <jats:italic>p</jats:italic> < 0.001). The cases increased most between 2015 and 2016 from 277 to 502 cases (81.2%). The number of hospitals offering these surgeries expanded from 24 in 2006 to 29 in 2022 (21% increase; <jats:italic>p</jats:italic> < 0.001).ConclusionThis study demonstrates an exponential growth in numbers feminizing and masculinizing of GAS performed each year in Germany. Furthermore, a discernible trend emerges with a propensity for concentration of procedures within selected high‐caseload centers across Germany.","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"106 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268781","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}
Alexandra Keller, McKenna Maus, Emma Keller, Karl Kerns
BackgroundBoar semen quality emphasizes three major criteria: sperm concentration, motility, and morphology. Methods to analyze concentration and motility quickly and objectively readily exist, but few exist for analyzing morphology outside of subjective manual counting. Other vital factors for fertilization, like acrosome health, lack efficient detection methods due to limitations in detection by the human eye and costly biomarker analysis, which is rarely used in semen diagnostics.ObjectiveTo overcome these challenges, we propose a novel approach integrating deep‐learning technology with high‐throughput image‐based flow cytometry (IBFC) for objective and accurate analysis of both morphology and label‐free acrosome health of thousands of individual spermatozoa at once, as opposed to manually counting on a microscope slide.Materials and methodsImages of 10,000 spermatozoa were captured using an IBFC and manually annotated based on the primary morphological defect or acrosome health status for the training of the convolutional neural network (CNN). The CNN used these images to train and then applied that training to unannotated images to predict the model accuracy.ResultsUsing the CNNs, high F1 scores of 96.73%, 98.55%, and 99.31% for 20x, 40x, and 60x magnifications, respectively, for morphological classification were attained. Additionally, the model demonstrates an F1 score of 99.8% in detecting subtle acrosome health variations at the 60x magnification.Discussion and conclusionsWe have established an integrated approach to rapidly collect and classify morphological defects and acrosome health status, without the use of manual counting or biomarker labeling. Our study underscores the potential of artificial intelligence in semen diagnostics, reducing technician variability, streamlining assays, and facilitating the development of additional label‐free detection methods. This innovative approach addresses the barriers hindering biomarker adoption in semen analysis, offering a promising avenue for enhancing reproductive health assessments.
背景公猪精液质量强调三个主要标准：精子浓度、活力和形态。目前已有快速客观地分析精子浓度和活力的方法，但除了主观的人工计数外，很少有分析形态的方法。为了克服这些挑战，我们提出了一种将深度学习技术与高通量图像流式细胞术（IBFC）相结合的新方法，可一次性客观准确地分析数千个精子的形态和无标记顶体健康状况，而无需在显微镜载玻片上手动计数。材料与方法使用 IBFC 采集 10,000 个精子的图像，并根据主要形态缺陷或顶体健康状况进行人工标注，用于训练卷积神经网络（CNN）。结果使用卷积神经网络，在 20 倍、40 倍和 60 倍放大率下，形态分类的 F1 分数分别达到 96.73%、98.55% 和 99.31%。此外，该模型在 60x 放大倍率下检测细微顶体健康变化的 F1 得分为 99.8%。讨论与结论我们建立了一种综合方法，可快速收集形态缺陷和顶体健康状况并进行分类，而无需使用人工计数或生物标记标记。我们的研究强调了人工智能在精液诊断中的潜力，它可以减少技术人员的变异性，简化检测过程，促进更多无标记检测方法的开发。这种创新方法解决了精液分析中采用生物标记物的障碍，为加强生殖健康评估提供了一条前景广阔的途径。
{"title":"Deep learning classification method for boar sperm morphology analysis","authors":"Alexandra Keller, McKenna Maus, Emma Keller, Karl Kerns","doi":"10.1111/andr.13758","DOIUrl":"https://doi.org/10.1111/andr.13758","url":null,"abstract":"BackgroundBoar semen quality emphasizes three major criteria: sperm concentration, motility, and morphology. Methods to analyze concentration and motility quickly and objectively readily exist, but few exist for analyzing morphology outside of subjective manual counting. Other vital factors for fertilization, like acrosome health, lack efficient detection methods due to limitations in detection by the human eye and costly biomarker analysis, which is rarely used in semen diagnostics.ObjectiveTo overcome these challenges, we propose a novel approach integrating deep‐learning technology with high‐throughput image‐based flow cytometry (IBFC) for objective and accurate analysis of both morphology and label‐free acrosome health of thousands of individual spermatozoa at once, as opposed to manually counting on a microscope slide.Materials and methodsImages of 10,000 spermatozoa were captured using an IBFC and manually annotated based on the primary morphological defect or acrosome health status for the training of the convolutional neural network (CNN). The CNN used these images to train and then applied that training to unannotated images to predict the model accuracy.ResultsUsing the CNNs, high F1 scores of 96.73%, 98.55%, and 99.31% for 20x, 40x, and 60x magnifications, respectively, for morphological classification were attained. Additionally, the model demonstrates an F1 score of 99.8% in detecting subtle acrosome health variations at the 60x magnification.Discussion and conclusionsWe have established an integrated approach to rapidly collect and classify morphological defects and acrosome health status, without the use of manual counting or biomarker labeling. Our study underscores the potential of artificial intelligence in semen diagnostics, reducing technician variability, streamlining assays, and facilitating the development of additional label‐free detection methods. This innovative approach addresses the barriers hindering biomarker adoption in semen analysis, offering a promising avenue for enhancing reproductive health assessments.","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"37 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252709","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}
BackgroundChronic periodontitis may induce erectile dysfunction (ED), however, the specific mechanism involved is unclear. The endothelial glycocalyx (eGlx) is a structure that can regulate endothelial nitric oxide synthase (eNOS) phosphorylation on the cavity surface of vessels.AimTo investigate whether chronic periodontitis leads to ED by affecting the eGlx.MethodsTwenty‐four 4‐week‐old male Sprague‒Dawley rats were randomly divided into four groups (n = 6): the control group, chronic periodontitis group, chronic periodontitis + heparin group (subcutaneous heparin 200 U/kg/day, 7 days), and control + heparin group. Four weeks after the induction of periodontitis in the rats, the maximum intra‐cavernous pressure/mean arterial pressure (ICPmax/MAP), serum C‐reactive protein (CRP), tumor necrosis factor alpha (TNF‐α), interleukin‐6 (IL‐6), nitric oxide (NO), heparin sulfate (HS), syndecan‐1 (SDC‐1), heparanase (HPSE), eNOS, and phosphor‐eNOS (p‐eNOS) concentration were measured, and the eGlx of the penile corpus cavernosum was observed by transmission electron microscopy (TEM).OutcomesChronic periodontitis can degrade eGlx on the rat penile corpus cavernosum by increasing serum CRP, TNF‐α, and IL‐6 levels, reducing the p‐eNOS/eNOS ratio and the NO concentration in the penile corpus cavernosum, and resulting in the inhibition of the erectile function.ResultsSerum CRP, TNF‐α, and IL‐6 levels and HPSE expression in penile cavernous tissue were significantly greater in the chronic periodontitis group than in the control group and the chronic periodontitis + heparin group (P < 0.05). The average thickness of the eGlx muscle in the penile corpus cavernosum in the chronic periodontitis group was significantly lower than those in the control group and chronic periodontitis + heparin group (P < 0.05). The HS concentration, SDC‐1 expression, p‐eNOS/eNOS, NO concentration, and ICPmax/MAP in the chronic periodontitis group were significantly lower than those in the control group and chronic periodontitis+ heparin group (P < 0.01).Clinical implicationsThe eGlx on penile cavernosum vessels may be a new therapeutic target for the treatment of ED.Strengths and limitationsThis study revealed that chronic periodontitis promotes the decomposition of vascular eGlx in the rat penile corpus cavernosum, however, it is not clear whether chronic periodontitis inhibits the synthesis of eGlx.ConclusionChronic periodontitis can degrade eGlx on the rat penile corpus cavernosum by increasing serum CRP, TNF‐α, and IL‐6 levels, reducing the p‐eNOS/eNOS ratio and the NO concentration in penile cavernous tissue, and resulting in the inhibition of the erectile function. Heparin inhibited eGlx decomposition and improved erectile function in rats with chronic periodontitis.
{"title":"Effect of chronic periodontitis on the endothelial glycocalyx of rat penile corpus cavernosum","authors":"Yuanhang Xia, Yang Zeng, Rui Jiang","doi":"10.1111/andr.13765","DOIUrl":"https://doi.org/10.1111/andr.13765","url":null,"abstract":"BackgroundChronic periodontitis may induce erectile dysfunction (ED), however, the specific mechanism involved is unclear. The endothelial glycocalyx (eGlx) is a structure that can regulate endothelial nitric oxide synthase (eNOS) phosphorylation on the cavity surface of vessels.AimTo investigate whether chronic periodontitis leads to ED by affecting the eGlx.MethodsTwenty‐four 4‐week‐old male Sprague‒Dawley rats were randomly divided into four groups (<jats:italic>n</jats:italic> = 6): the control group, chronic periodontitis group, chronic periodontitis + heparin group (subcutaneous heparin 200 U/kg/day, 7 days), and control + heparin group. Four weeks after the induction of periodontitis in the rats, the maximum intra‐cavernous pressure/mean arterial pressure (ICPmax/MAP), serum C‐reactive protein (CRP), tumor necrosis factor alpha (TNF‐α), interleukin‐6 (IL‐6), nitric oxide (NO), heparin sulfate (HS), syndecan‐1 (SDC‐1), heparanase (HPSE), eNOS, and phosphor‐eNOS (p‐eNOS) concentration were measured, and the eGlx of the penile corpus cavernosum was observed by transmission electron microscopy (TEM).OutcomesChronic periodontitis can degrade eGlx on the rat penile corpus cavernosum by increasing serum CRP, TNF‐α, and IL‐6 levels, reducing the p‐eNOS/eNOS ratio and the NO concentration in the penile corpus cavernosum, and resulting in the inhibition of the erectile function.ResultsSerum CRP, TNF‐α, and IL‐6 levels and HPSE expression in penile cavernous tissue were significantly greater in the chronic periodontitis group than in the control group and the chronic periodontitis + heparin group (<jats:italic>P</jats:italic> < 0.05). The average thickness of the eGlx muscle in the penile corpus cavernosum in the chronic periodontitis group was significantly lower than those in the control group and chronic periodontitis + heparin group (<jats:italic>P</jats:italic> < 0.05). The HS concentration, SDC‐1 expression, p‐eNOS/eNOS, NO concentration, and ICPmax/MAP in the chronic periodontitis group were significantly lower than those in the control group and chronic periodontitis+ heparin group (<jats:italic>P</jats:italic> < 0.01).Clinical implicationsThe eGlx on penile cavernosum vessels may be a new therapeutic target for the treatment of ED.Strengths and limitationsThis study revealed that chronic periodontitis promotes the decomposition of vascular eGlx in the rat penile corpus cavernosum, however, it is not clear whether chronic periodontitis inhibits the synthesis of eGlx.ConclusionChronic periodontitis can degrade eGlx on the rat penile corpus cavernosum by increasing serum CRP, TNF‐α, and IL‐6 levels, reducing the p‐eNOS/eNOS ratio and the NO concentration in penile cavernous tissue, and resulting in the inhibition of the erectile function. Heparin inhibited eGlx decomposition and improved erectile function in rats with chronic periodontitis.","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"42 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252708","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}
Juan Yang, Xiangying Ou, Huihong Zeng, Lijian Shao
BackgroundPrevious studies have shown that the activation of p38MAPK signaling plays a crucial role in regulating gonadal cell fate decisions in both mouse and human. Excessive activation of p38MAPK by radiation significantly causes testicular damage and negatively affects the male reproductive function. Therefore, fine‐tuned regulation of p38MAPK signaling is critical in both physiological and pathological conditions.ResultThis review summarizes the impact of p38MAPK signaling on testicular germ cells and microenvironment under normal condition. The relationship between radiation, reactive oxygen species (ROS), and p38MAPK is summarized. In conclusion, radiation exposure triggers the overactivation of p38MAPK, which is regulated by ROS, resulting in testicular damage. Various p38MAPK‐targeting agents are discussed, providing guidance for developing new strategies.
{"title":"A comprehensive review on p38MAPK signaling as a potent radioprotector in testis","authors":"Juan Yang, Xiangying Ou, Huihong Zeng, Lijian Shao","doi":"10.1111/andr.13760","DOIUrl":"https://doi.org/10.1111/andr.13760","url":null,"abstract":"BackgroundPrevious studies have shown that the activation of p38MAPK signaling plays a crucial role in regulating gonadal cell fate decisions in both mouse and human. Excessive activation of p38MAPK by radiation significantly causes testicular damage and negatively affects the male reproductive function. Therefore, fine‐tuned regulation of p38MAPK signaling is critical in both physiological and pathological conditions.ResultThis review summarizes the impact of p38MAPK signaling on testicular germ cells and microenvironment under normal condition. The relationship between radiation, reactive oxygen species (ROS), and p38MAPK is summarized. In conclusion, radiation exposure triggers the overactivation of p38MAPK, which is regulated by ROS, resulting in testicular damage. Various p38MAPK‐targeting agents are discussed, providing guidance for developing new strategies.","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"1 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252710","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}
BackgroundTesticular germ cell tumors (TGCTs), derived from primordial germ cells, are rare malignancies with high curative potential. However, the emergence of new evidence indicating that 15% of patients experience tumor progression, leading to death, underscores the need for innovative therapeutics.ObjectivesThis review aimed to explore the immune status in maintaining testicular health and the immune‐related aspects of malignancy. Furthermore, it presents an overview of current data on the use of immunotherapy for TGCT patients.Results DiscussionRecent advances in immunology have opened a promising avenue for studying diseases and highlighted its role in treating diseases. While the immunopathological facets of TGCTs are not fully understood, investigations suggest a complex interplay among testis‐resident immune cells, testis‐specific cells (i.e., Sertoli cells (SCs) and Leydig cells (LCs)), and immune‐regulating mediators (e.g., sex hormones) in the normal testicle that foster the testicular immune privilege (TIP). Although TIP plays a crucial role in sperm production, it also makes testis vulnerable to tumor development. In the context of cancer‐related inflammation, disruption of TIP leads to an imbalanced immune response, resulting in chronic inflammation that can contribute to testicular tissue dysfunction or loss, potentially aiding in cancer invasion and progression.ConclusionComparing the immune profiles of normal and malignant testes is valuable and may provide insights into different aspects of testicular immunity and immune‐based treatment approaches. For patients resistant to chemotherapy and with a poor prognosis, immunotherapy has shown promising results. However, its effectiveness in treating resistant TGCTs or preventing tumor recurrence is still uncertain.
背景睾丸生殖细胞瘤（TGCT）源自原始生殖细胞，是一种罕见的恶性肿瘤，具有很高的治愈潜力。本综述旨在探讨维持睾丸健康的免疫状态以及恶性肿瘤的免疫相关方面。结果 讨论免疫学的最新进展为研究疾病开辟了一条前景广阔的途径，并凸显了其在治疗疾病中的作用。尽管TGCT的免疫病理机制尚未完全明了，但研究表明，睾丸驻留的免疫细胞、睾丸特异性细胞（即Sertoli细胞（SC）和Leydig细胞（LC））以及正常睾丸中的免疫调节介质（如性激素）之间存在着复杂的相互作用，从而形成了睾丸免疫特权（TIP）。尽管 TIP 在精子生成过程中发挥着至关重要的作用，但它也使睾丸易受肿瘤发展的影响。在与癌症相关的炎症背景下，TIP 的破坏会导致免疫反应失衡，造成慢性炎症，从而导致睾丸组织功能障碍或丧失，并有可能助长癌症的侵袭和发展。对于化疗耐药且预后不良的患者，免疫疗法已显示出良好的效果。然而，免疫疗法在治疗耐药的TGCT或预防肿瘤复发方面的有效性仍不确定。
{"title":"Unwrapping the immunological alterations in testicular germ cell tumors: From immune homeostasis to malignancy and emerging immunotherapies","authors":"Hadiseh Farahani, Reza Darvishvand, Aida Khademolhosseini, Nasrollah Erfani","doi":"10.1111/andr.13751","DOIUrl":"https://doi.org/10.1111/andr.13751","url":null,"abstract":"BackgroundTesticular germ cell tumors (TGCTs), derived from primordial germ cells, are rare malignancies with high curative potential. However, the emergence of new evidence indicating that 15% of patients experience tumor progression, leading to death, underscores the need for innovative therapeutics.ObjectivesThis review aimed to explore the immune status in maintaining testicular health and the immune‐related aspects of malignancy. Furthermore, it presents an overview of current data on the use of immunotherapy for TGCT patients.Results DiscussionRecent advances in immunology have opened a promising avenue for studying diseases and highlighted its role in treating diseases. While the immunopathological facets of TGCTs are not fully understood, investigations suggest a complex interplay among testis‐resident immune cells, testis‐specific cells (i.e., Sertoli cells (SCs) and Leydig cells (LCs)), and immune‐regulating mediators (e.g., sex hormones) in the normal testicle that foster the testicular immune privilege (TIP). Although TIP plays a crucial role in sperm production, it also makes testis vulnerable to tumor development. In the context of cancer‐related inflammation, disruption of TIP leads to an imbalanced immune response, resulting in chronic inflammation that can contribute to testicular tissue dysfunction or loss, potentially aiding in cancer invasion and progression.ConclusionComparing the immune profiles of normal and malignant testes is valuable and may provide insights into different aspects of testicular immunity and immune‐based treatment approaches. For patients resistant to chemotherapy and with a poor prognosis, immunotherapy has shown promising results. However, its effectiveness in treating resistant TGCTs or preventing tumor recurrence is still uncertain.","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"24 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142185808","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}
BackgroundTesticular torsion/detorsion can cause testis loss and infertility. Aloperine is a major active alkaloid extracted from Sophora alopecuroides Linn. It has been shown to have organ‐protective effects. However, the effects of aloperine on the testis and its underlying mechanisms remain unclear.ObjectivesThis study investigated the effect of aloperine on testicular torsion/detorsion injury in rats.Materials and MethodsMale Sprague‐Dawley rats were randomized to the sham‐operated (sham), testicular I/R (TI/R), or aloperine preconditioning (ALOPre) or postconditioning (ALOPost) groups. All rats except for the sham‐operated rats were subjected to 3 h of right spermatic cord torsion (720°, clockwise), followed by 3 h of detorsion. Aloperine (10 mg/kg) was intravenously administered before testicular torsion (ALOPre) or at the onset of testicular detorsion (ALOPost). The therapeutic efficacy of aloperine was evaluated by histological analysis, oxidative stress evaluation, inflammatory response examination, apoptosis analysis, protein analysis, and immunohistological assessment.ResultsCompared with TI/R, aloperine protected both the ipsilateral and contralateral testes against unilateral testicular I/R, as evidenced by a reduced testicular weight to body weight (TW/BW) ratio (ALOPre: p = 0.0037; ALOPost: p = 0.0021) and volume (ALOPre: p = 0.0020; ALOPost: p = 0.0009), less structural damage with better Johnsen (ALOPre: p = 0.0013; ALOPost: p = 0.0021), and Cosentino scores (ALOPre: p < 0.0001; ALOPost: p < 0.0001), increased mean seminiferous tubule diameter and mean seminiferous tubule epithelial height, decreased testicular apoptosis, and less oxidative stress and inflammatory response. In addition, aloperine significantly stimulated the phosphorylation of signal transducer and activator of transcription (STAT)‐3 in the ipsilateral testes following detorsion. Administration of Ag490 suppressed STAT‐3 phosphorylation, thereby abrogating the protective effects exerted by aloperine on the ipsilateral testis.Discussion and ConclusionAloperine has a strong testicular protective effect on the ipsilateral and contralateral testes after testicular torsion/detorsion. This aloperine‐induced ipsilateral testicular protection is mediated via the STAT‐3 signaling pathway.
{"title":"Aloperine protects the testis against testicular ischemia/reperfusion injury in rats","authors":"Shichao Wei, Junshen Xiao, Feng Ju, Zhaoyang Hu","doi":"10.1111/andr.13750","DOIUrl":"https://doi.org/10.1111/andr.13750","url":null,"abstract":"BackgroundTesticular torsion/detorsion can cause testis loss and infertility. Aloperine is a major active alkaloid extracted from <jats:italic>Sophora alopecuroides</jats:italic> Linn. It has been shown to have organ‐protective effects. However, the effects of aloperine on the testis and its underlying mechanisms remain unclear.ObjectivesThis study investigated the effect of aloperine on testicular torsion/detorsion injury in rats.Materials and MethodsMale Sprague‐Dawley rats were randomized to the sham‐operated (sham), testicular I/R (TI/R), or aloperine preconditioning (ALOPre) or postconditioning (ALOPost) groups. All rats except for the sham‐operated rats were subjected to 3 h of right spermatic cord torsion (720°, clockwise), followed by 3 h of detorsion. Aloperine (10 mg/kg) was intravenously administered before testicular torsion (ALOPre) or at the onset of testicular detorsion (ALOPost). The therapeutic efficacy of aloperine was evaluated by histological analysis, oxidative stress evaluation, inflammatory response examination, apoptosis analysis, protein analysis, and immunohistological assessment.ResultsCompared with TI/R, aloperine protected both the ipsilateral and contralateral testes against unilateral testicular I/R, as evidenced by a reduced testicular weight to body weight (TW/BW) ratio (ALOPre: <jats:italic>p </jats:italic>= 0.0037; ALOPost: <jats:italic>p </jats:italic>= 0.0021) and volume (ALOPre: <jats:italic>p </jats:italic>= 0.0020; ALOPost: <jats:italic>p </jats:italic>= 0.0009), less structural damage with better Johnsen (ALOPre: <jats:italic>p </jats:italic>= 0.0013; ALOPost: <jats:italic>p </jats:italic>= 0.0021), and Cosentino scores (ALOPre: <jats:italic>p </jats:italic>< 0.0001; ALOPost: <jats:italic>p </jats:italic>< 0.0001), increased mean seminiferous tubule diameter and mean seminiferous tubule epithelial height, decreased testicular apoptosis, and less oxidative stress and inflammatory response. In addition, aloperine significantly stimulated the phosphorylation of signal transducer and activator of transcription (STAT)‐3 in the ipsilateral testes following detorsion. Administration of Ag490 suppressed STAT‐3 phosphorylation, thereby abrogating the protective effects exerted by aloperine on the ipsilateral testis.Discussion and ConclusionAloperine has a strong testicular protective effect on the ipsilateral and contralateral testes after testicular torsion/detorsion. This aloperine‐induced ipsilateral testicular protection is mediated via the STAT‐3 signaling pathway.","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"9 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142224414","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}
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