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The effects of kidney transplantation on sex hormones, sperm parameters, and fertility rate in males: A systematic review. 肾移植对男性性激素、精子参数和生育率的影响:系统综述。
IF 3.2 2区 医学 Q1 ANDROLOGY Pub Date : 2025-07-11 DOI: 10.1111/andr.70097
Berk Hazir, Hakan Bahadir Haberal, Meylis Artykov, Muhammet Irfan Donmez, Alicia López-Abad, Alessio Pecoraro, Beatriz Bañuelos Marco, Thomas Prudhomme, Alberto Piana, Daniar Osmonov, Murat Gul, Angelo Territo

Background: End-stage renal disease (ESRD) is reported to be associated with the impairment of sex hormones, including decreased testosterone levels and increased follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin levels. Additionally, patients with ESRD often experience impaired spermatogenesis, leading to infertility. However, variations in study methodologies and reported outcomes make it challenging to draw definitive conclusions. Therefore, this study aims to evaluate the effects of kidney transplantation (KT) on these issues, which can be useful in counseling male patients with ESRD.

Methods: A systematic search was conducted in Web of Science, Medline (via PubMed), and Embase (via Scopus) to identify peer-reviewed studies evaluating the impact of KT on sex hormones and reproductive parameters. A systematic review (SR) was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This review included English-language articles published between January 1975 and December 2024. Excluded from this search were reviews, editorials, book chapters, conference abstracts, case reports, and case series with up to four patients were excluded.

Results: A total of 2939 publications were initially identified, and 23 studies met the inclusion criteria, comprising 738 patients for analysis. Most studies reported a significant increase in testosterone levels 3, 6, and 12 months post-KT. LH and prolactin levels exhibited a trend parallel to that of testosterone. A statistically significant decrease in LH levels was observed at both 1 and 12 months post-KT, while prolactin levels showed a significant reduction at all evaluated time points from 1 to 12 months. In contrast, FSH levels fluctuated over time and did not demonstrate statistical significance at any assessment point. Additionally, KT led to improvements in testis biopsy findings, and all categories of sperm parameters.

Conclusion: This SR demonstrates that KT improves sex hormone levels, sperm parameters, and sexual function in male kidney recipients. However, to gain a more comprehensive understanding of the sexual health of male kidney recipients, the establishment of an international database with prospectively collected data is warranted.

背景:据报道,终末期肾病(ESRD)与性激素的损害有关,包括睾酮水平降低、促卵泡激素(FSH)、促黄体生成素(LH)和催乳素水平升高。此外,ESRD患者经常经历精子发生受损,导致不孕。然而,研究方法和报告结果的差异使得得出明确的结论具有挑战性。因此,本研究旨在评估肾移植(KT)对这些问题的影响,为男性ESRD患者提供咨询。方法:系统检索Web of Science、Medline(通过PubMed)和Embase(通过Scopus),以确定评估KT对性激素和生殖参数影响的同行评审研究。按照系统评价和荟萃分析(PRISMA)指南的首选报告项目进行系统评价(SR)。该综述包括1975年1月至2024年12月期间发表的英文文章。本检索排除了综述、社论、书籍章节、会议摘要、病例报告和最多4例患者的病例系列。结果:最初共纳入2939篇文献,23篇研究符合纳入标准,共纳入738例患者。大多数研究报告在kt后3、6和12个月睾酮水平显著增加。LH和催乳素水平表现出与睾酮水平平行的趋势。在kt后1个月和12个月,LH水平均有统计学意义上的显著下降,而催乳素水平在1 - 12个月的所有评估时间点均有显著下降。相比之下,FSH水平随时间波动,在任何评估点都没有统计学意义。此外,KT改善了睾丸活检结果和所有类别的精子参数。结论:本研究表明,KT可改善男性肾受体的性激素水平、精子参数和性功能。然而,为了更全面地了解男性肾受体的性健康,有必要建立一个具有前瞻性收集数据的国际数据库。
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引用次数: 0
Gonadotropin storage and trafficking. 促性腺激素的储存和贩运。
IF 3.2 2区 医学 Q1 ANDROLOGY Pub Date : 2025-07-11 DOI: 10.1111/andr.70094
Asia Ingram, T Rajendra Kumar

Background: Gonadotropins are synthesized in gonadotropes of the anterior pituitary, and they orchestrate reproductive function in vertebrates. LH and FSH share a common α-subunit that is non-covalently associated with a hormone - and receptor-specific β-subunit. Despite synthesized in the same cell, i.e., gonadotrope the trafficking and secretion patterns of LH and FSH are distinct. FSH is mostly constitutively secreted, whereas LH is stored in dense core granules and is released as a bolus via the regulated pathway in response to gonadotropin-releasing hormone.

Objective: To comparatively review the storage and secretion patterns of gonadotropins in vertebrates.

Materials and methods: Gonadotropin storage patterns are comparatively analyzed in vertebrates starting from primitive fish all the way up to higher mammals. The published work on gonadotropin trafficking/secretion patterns using in vitro and in vivo approaches is critically discussed.

Results: Primitive fish (lampreys and hagfish) express a single gonadotropic hormone. From these early vertebrates, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) have evolved as two distinct hormones. In several species, including teleost fish, monohormonal gonadotropes are present that express either LH or FSH. In higher vertebrates, the majority of the gonadotropes (>90%) are bihormonal and contain both LH and FSH. Both in vitro (cell transfection and expression) and in vivo (transgenic mouse) studies identified that the LHβ caroboxy terminus heptapeptide is a gonadotrope-specific regulated pathway sorting determinant.

Discussion: When FSH is genetically rerouted from the constitutive trafficking mode and is engineered (LHβ heptapeptide fused to FSHβ subunit) to exit via the regulated pathway in gonadotropes of transgenic mice, it resulted in enhanced ovulations due to suppression of atresia and apoptosis and increased pro-survival pathways in ovaries. However, rerouted FSH expressing male mice did not demonstrate any gain of function phenotypes.

Conclusion: Understanding the basic molecular mechanisms of gonadotropin storage/trafficking and secretion may eventually lead to clinical benefits of enhancing female reproductive function and reproductive lifespan.

背景:促性腺激素是在垂体前叶的促性腺中合成的,它们协调着脊椎动物的生殖功能。LH和FSH有一个共同的α-亚基,该亚基与激素和受体特异性β-亚基非共价相关。促性腺激素虽然在同一细胞中合成,但LH和FSH的运输和分泌模式不同。FSH主要是组成性分泌,而LH则储存在致密的核心颗粒中,并通过受促性腺激素释放激素调节的途径作为丸剂释放。目的:比较研究脊椎动物促性腺激素的储存和分泌规律。材料和方法:比较分析了从原始鱼类到高等哺乳动物的脊椎动物的促性腺激素储存模式。已发表的关于促性腺激素贩运/分泌模式使用体外和体内方法的工作进行了批判性讨论。结果:原始鱼类(七鳃鳗和盲鳗)表达单一促性腺激素。从这些早期的脊椎动物,黄体生成素(LH)和卵泡刺激素(FSH)已经进化成两种不同的激素。在包括硬骨鱼在内的一些鱼类中,存在表达LH或FSH的单激素促性腺激素。在高等脊椎动物中,大多数促性腺激素(约90%)是双激素,同时含有LH和FSH。体外(细胞转染和表达)和体内(转基因小鼠)研究均发现,LHβ羧基末端七肽是促性腺激素特异性调控通路分选的决定因素。讨论:在促性腺激素转基因小鼠中,当FSH从组成运输模式中被遗传改变并被改造(LHβ七肽融合到FSHβ亚基)通过受调节的途径排出时,由于抑制卵巢闭锁和细胞凋亡以及增加促存活途径,导致排卵增强。然而,重定向表达FSH的雄性小鼠没有表现出任何功能表型的增加。结论:了解促性腺激素储存、转运和分泌的基本分子机制,有助于提高女性生殖功能和延长生殖寿命。
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引用次数: 0
Adjuvant-induced arthritis induces epithelial proliferation and differential expression of SVS2 and SVS3 in the seminal vesicles 佐剂性关节炎诱导精囊上皮细胞增殖和SVS2和SVS3的差异表达。
IF 3.4 2区 医学 Q1 ANDROLOGY Pub Date : 2025-07-07 DOI: 10.1111/andr.70085
Thamires Miyako Ito Sigole, Camila Reis Santos, Isabela Fiorentino Souza Nascimento, Erick J. R. Silva, Agnaldo Bruno Chies, Maria Angélica Spadella
<div> <section> <h3> Background</h3> <p>Rheumatoid arthritis (RA) is an inflammatory disease triggered by chronic and systemic activation of the immune system, with consequences for male fertility. However, the influence of RA on sexual accessory glands remains poorly investigated.</p> </section> <section> <h3> Objectives</h3> <p>This study evaluated the late impact of adjuvant-induced arthritis (AIA) on the morphophysiology of the seminal vesicles and verified whether these effects can be influenced by androgen deprivation.</p> </section> <section> <h3> Materials and methods</h3> <p>Adult male Wistar rats were allocated into four experimental groups and subjected to induction of AIA (via injection of <i>Mycobacterium tuberculosis</i> in the right hind paw), orchiectomy (ORX), both procedures (ORX/AIA), or neither (SHAM). Forty days after AIA induction, the seminal vesicles were processed for histopathological and morphometric-stereological analysis. Collagen deposition was measured, and immunostaining was conducted to determine PCNA, SVS2, and SVS3 expression. Serum testosterone was determined at 15 and 40 days after AIA induction.</p> </section> <section> <h3> Results</h3> <p>Body mass and wet weight of the seminal vesicles decreased in the AIA-induced and orchiectomized groups, and testosterone levels decreased in the AIA group. Collagen deposition in the seminal vesicle stroma increased in the orchiectomized rats, but not in the AIA rats. Induction of AIA promoted cellular proliferation in the distal region of the seminal vesicles in both intact and orchiectomized rats, and levels of two significant secretory proteins in the vesicle also changed with AIA: SVS2 increased, while SVS3 decreased. Conversely, orchiectomy decreased the expression of both SVS2 and SVS3.</p> </section> <section> <h3> Discussion</h3> <p>The late impact of AIA on seminal vesicle parameters appears to be compensated by an increase in epithelial cell proliferation and changes in secretory activity, in an androgen-dependent manner.</p> </section> <section> <h3> Conclusion</h3> <p>The data suggest that transient arthritic hypoandrogenism and the direct action of joint inflammatory mediators may influence the seminal vesicle activity. Further research is required to better address the repercussions of arthritis on male fertility.</p> </section> </di
背景:类风湿关节炎(RA)是一种由免疫系统慢性和全身性激活引发的炎症性疾病,对男性生育能力有影响。然而,类风湿关节炎对性腺的影响尚不清楚。目的:本研究评估了佐剂诱导的关节炎(AIA)对精囊形态生理的晚期影响,并验证了这些影响是否会受到雄激素剥夺的影响。材料与方法:将成年雄性Wistar大鼠分为4个实验组,分别进行AIA诱导(右后爪注射结核分枝杆菌)、睾丸切除术(ORX)、两种手术(ORX/AIA)或两种手术均不进行(SHAM)。AIA诱导后40天,对精囊进行组织病理学和形态计量学-体视学分析。测定胶原沉积,免疫染色检测PCNA、SVS2和SVS3的表达。在AIA诱导后15天和40天测定血清睾酮水平。结果:AIA诱导组和去睾丸组精囊体质量和湿重下降,AIA组睾酮水平下降。去睾丸大鼠精囊间质胶原沉积增加,而AIA大鼠无。AIA的诱导促进了完整和切除睾丸大鼠精囊远端区域的细胞增殖,并且精囊中两种重要分泌蛋白的水平也随着AIA的变化而变化:SVS2升高,SVS3降低。相反,睾丸切除术降低了SVS2和SVS3的表达。讨论:AIA对精囊参数的晚期影响似乎通过上皮细胞增殖的增加和分泌活性的改变来补偿,以雄激素依赖的方式。结论:一过性关节炎雄激素低下和关节炎症介质的直接作用可能影响精囊活性。需要进一步的研究来更好地解决关节炎对男性生育能力的影响。
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引用次数: 0
Pharmacokinetics, pharmacodynamics, and safety interaction study of tunodafil hydrochloride and alcohol: A randomized, blinded, placebo-controlled, three-cycle crossover study in Chinese healthy men 盐酸妥达非和酒精的药代动力学、药效学和安全性相互作用研究:一项随机、盲法、安慰剂对照、三周期交叉研究。
IF 3.4 2区 医学 Q1 ANDROLOGY Pub Date : 2025-07-07 DOI: 10.1111/andr.70083
Dingyuan Hu, Suping Niu, Fan Huang, Lu Jin, Qun Gu, Yanting Li, Chongyou Lee, Zhenwei Xie, Xiangxing Liu, Fang Men, Wenyan Zhao, Shuang Li, Yian Liu, Qian Wang, Huaying Fan, Jiaojiao Zhang, Shuangshuang Lin, Liming Chen, Yi Fang

Objectives

This study aimed to evaluate the pharmacodynamic effects of administering tunodafil hydrochloride with alcohol on blood pressure and heart rate in healthy Chinese males, and to investigate the mutual pharmacokinetic interactions and safety of the combination.

Methods

The trial was a randomized, blinded, placebo-controlled, three-cycle crossover design, with one administration in each cycle and a 7-day washout interval between cycles. Eighteen healthy men were randomized to receive tunodafil hydrochloride with an alcoholic beverage, placebo with an alcoholic beverage, or tunodafil hydrochloride with a placebo beverage in each cycle. The primary endpoints included plasma concentrations of tunodafil, metabolite M459, and alcohol, as well as supine blood pressure and heart rate measurements. The secondary endpoint was the incidence of adverse events.

Results

Pharmacokinetic results demonstrated that the combined drug and alcohol group did not affect plasma alcohol concentration compared to alcohol alone. However, co-administration led to increased systemic exposure of tunodafil and its metabolite M459: AUC0-∞ rose by 42.89% and 28.75%, while Cmax increased by 74.46% and 39.32%, respectively, compared to the drug alone group. Pharmacodynamic analysis indicated that the reduction in blood pressure was primarily driven by alcohol consumption, with no significant additional effect from tunodafil co-administration. In contrast, heart rate elevation was notably amplified when both drug and alcohol were given together, exceeding the effects of either substance alone. Safety results reported 149 grade-one adverse events.

Conclusion

The study concluded that tunodafil hydrochloride, when taken with alcohol, does not interfere with alcohol metabolism but moderately enhances the tunodafil and metabolite exposure. Alcohol remained the dominant factor in lowering blood pressure, while tunodafil contributed to an additive increase in heart rate. The combination does not significantly increase adverse events.

目的:本研究旨在评价盐酸妥诺他非与酒精联合用药对中国健康男性血压和心率的药效学影响,并探讨两者的相互药动学相互作用和联合用药的安全性。方法:该试验采用随机、盲法、安慰剂对照、三周期交叉设计,每个周期一次给药,两个周期之间有7天的洗脱期。在每个周期中,18名健康男性随机接受盐酸妥诺他非与酒精饮料,安慰剂与酒精饮料,或盐酸妥诺他非与安慰剂饮料。主要终点包括妥诺非、代谢物M459和酒精的血浆浓度,以及仰卧位血压和心率测量。次要终点是不良事件的发生率。结果:药代动力学结果表明,与单独使用酒精相比,药物和酒精联合使用组对血浆酒精浓度没有影响。然而,与单独给药组相比,联合给药导致全身暴露量增加,tunnodafil及其代谢物M459: AUC0-∞分别增加42.89%和28.75%,Cmax分别增加74.46%和39.32%。药效学分析表明,血压的降低主要是由饮酒引起的,与妥诺他非同时服用没有显著的额外效果。相比之下,当药物和酒精同时服用时,心率升高明显增强,超过单独服用任何一种物质的效果。安全性结果报告了149例一级不良事件。结论:本研究结论盐酸妥诺他非与酒精一起服用时不会干扰酒精代谢,但会适度增加妥诺他非及其代谢物的暴露。酒精仍然是降低血压的主要因素,而妥诺非有助于增加心率。联合用药不会显著增加不良事件。
{"title":"Pharmacokinetics, pharmacodynamics, and safety interaction study of tunodafil hydrochloride and alcohol: A randomized, blinded, placebo-controlled, three-cycle crossover study in Chinese healthy men","authors":"Dingyuan Hu,&nbsp;Suping Niu,&nbsp;Fan Huang,&nbsp;Lu Jin,&nbsp;Qun Gu,&nbsp;Yanting Li,&nbsp;Chongyou Lee,&nbsp;Zhenwei Xie,&nbsp;Xiangxing Liu,&nbsp;Fang Men,&nbsp;Wenyan Zhao,&nbsp;Shuang Li,&nbsp;Yian Liu,&nbsp;Qian Wang,&nbsp;Huaying Fan,&nbsp;Jiaojiao Zhang,&nbsp;Shuangshuang Lin,&nbsp;Liming Chen,&nbsp;Yi Fang","doi":"10.1111/andr.70083","DOIUrl":"10.1111/andr.70083","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study aimed to evaluate the pharmacodynamic effects of administering tunodafil hydrochloride with alcohol on blood pressure and heart rate in healthy Chinese males, and to investigate the mutual pharmacokinetic interactions and safety of the combination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The trial was a randomized, blinded, placebo-controlled, three-cycle crossover design, with one administration in each cycle and a 7-day washout interval between cycles. Eighteen healthy men were randomized to receive tunodafil hydrochloride with an alcoholic beverage, placebo with an alcoholic beverage, or tunodafil hydrochloride with a placebo beverage in each cycle. The primary endpoints included plasma concentrations of tunodafil, metabolite M459, and alcohol, as well as supine blood pressure and heart rate measurements. The secondary endpoint was the incidence of adverse events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Pharmacokinetic results demonstrated that the combined drug and alcohol group did not affect plasma alcohol concentration compared to alcohol alone. However, co-administration led to increased systemic exposure of tunodafil and its metabolite M459: AUC<sub>0-∞</sub> rose by 42.89% and 28.75%, while <i>C</i><sub>max</sub> increased by 74.46% and 39.32%, respectively, compared to the drug alone group. Pharmacodynamic analysis indicated that the reduction in blood pressure was primarily driven by alcohol consumption, with no significant additional effect from tunodafil co-administration. In contrast, heart rate elevation was notably amplified when both drug and alcohol were given together, exceeding the effects of either substance alone. Safety results reported 149 grade-one adverse events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study concluded that tunodafil hydrochloride, when taken with alcohol, does not interfere with alcohol metabolism but moderately enhances the tunodafil and metabolite exposure. Alcohol remained the dominant factor in lowering blood pressure, while tunodafil contributed to an additive increase in heart rate. The combination does not significantly increase adverse events.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"14 2","pages":"466-479"},"PeriodicalIF":3.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/andr.70083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574683","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}
引用次数: 0
New three-dimensional nuclear morphometry tool quantifies impact of slow freezing on sperm hypercondensed chromatin. 新的三维核形态测量工具量化慢冷冻对精子高凝聚染色质的影响。
IF 3.2 2区 医学 Q1 ANDROLOGY Pub Date : 2025-07-04 DOI: 10.1111/andr.70096
Oriana Carcy, Sophie Desset, Tristan Dubos, Chloé Puceat, Maïssa Andrieux, Marine Compagnon, Gilles Sireta, Bruno Pereira, Florent Cachin, Aline V Probst, Christophe Tatout, Florence Brugnon, Hanae Pons-Rejraji

Background: Perm freezing compromises nuclear integrity. Standardized tools to assess three-dimensional (3D) chromatin alterations are lacking.

Objectives: This study aimed to present a novel protocol for 3D nuclear morphometric analysis of human spermatozoa to measure slow freezing and thawing-induced alterations.

Materials and methods: Human sperm cells were examined before and after freezing using a consistent 3D nuclear morphometric analysis protocol that distinguishes between live and dead spermatozoa. Morphometric assessments were performed by microscopy and image analysis with the NucleusJ2.0/NODeJ software, without introducing denaturing agents. The analysis included measurements of nuclear volume, elongation, flatness, and the volume of hypercondensed chromatin (Hc) regions, along with the relative fluorescence intensity of these zones (RHF intensity). Additional parameters evaluated comprised sperm vitality, motility, DNA fragmentation, and chromatin decondensation.

Results: A quantitative analysis of 4919 sperm nuclei from 10 patients demonstrated significant modifications in the hypercondensed chromatin (Hc) zones, with a marked decrease in sperm vitality and motility (p  <  0.001) and a significant increase in DNA fragmentation (p  <  0.05). At the chromatin level, slow freezing induced a higher number of Hc zones per nucleus (p  <  0.01), a reduction in the average volume of these zones (p  <  0.0001), and a reduced relative fluorescence intensity (p  <  0.01). Notably, these chromatin alterations were most pronounced in viable spermatozoa.

Discussion and conclusion: This study is the first to provide standardized 3D nuclear morphometry measurements for human sperm, offering a novel biomarker to assess male fertility and cryopreservation susceptibility, with potential clinical applications for improving patient care. Slow freeze-thaw cycle induced significant alterations in sperm chromatin, disrupting nuclear organization and forming several smaller, less compacted hypercondensed chromatin zones.

背景:烫发冷冻损害核的完整性。目前还缺乏评估三维(3D)染色质改变的标准化工具。目的:本研究旨在提出一种新的方案,用于人类精子的三维核形态分析,以测量缓慢冷冻和解冻引起的变化。材料和方法:在冷冻前后使用一致的3D核形态分析方案检查人类精子细胞,以区分活精子和死精子。形态学评估采用显微镜和NucleusJ2.0/NODeJ软件进行图像分析,未引入变性剂。分析包括核体积、伸长、平整度和高凝聚染色质(Hc)区域的体积,以及这些区域的相对荧光强度(RHF强度)的测量。评估的其他参数包括精子活力、活力、DNA片段和染色质去浓缩。结果:对来自10名患者的4919个精子核的定量分析显示,高凝聚染色质(Hc)区域发生了显著变化,精子活力和运动能力明显下降(p)。讨论和结论:这项研究首次为人类精子提供了标准化的3D核形态测量,为评估男性生育能力和低温保存敏感性提供了一种新的生物标志物,具有改善患者护理的潜在临床应用价值。缓慢的冻融循环诱导了精子染色质的显著改变,破坏了核组织,形成了几个更小、更不紧密的高浓缩染色质区。
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引用次数: 0
Proteomic profiling of porcine seminal extracellular vesicles reveals potential in vivo fertility biomarkers 猪精胞外囊泡的蛋白质组学分析揭示了潜在的体内生育生物标志物。
IF 3.4 2区 医学 Q1 ANDROLOGY Pub Date : 2025-07-04 DOI: 10.1111/andr.70089
Isabel Barranco, Pablo Martínez-Díaz, Ana Parra, María José Martínez-Alborcia, Xiomara Lucas, Heriberto Rodríguez-Martínez, Jordi Roca

Background

Predicting male fertility in farm animals remains a challenge. Seminal plasma (SP) contains a high amount of heterogeneous seminal extracellular vesicles (sEVs), believed involved in reproductive processes and maybe key to understanding male fertility.

Aims

To identify the sEV proteins that are differentially expressed between more and less fertile boars and that could be candidates for fertility biomarkers in boars used in artificial insemination (AI) programs.

Materials and methods

Small (S) and large (L) sEV subsets from SP samples of AI boars with differences in fertility: high (H) or low (L) farrowing rate (FR) and large (L) or small (S) litter size (LS). The S- and L-sEV subsets were isolated by size exclusion chromatography and characterized according to the Minimal Information for Studies of Extracellular Vesicles (MISEV2023) guidelines. Proteomic analyses (three biological replicates per fertility group and sEV subset) were performed using a Bruker timsTOF fleX™ instrument with data-independent acquisition parallel accumulation-serial fragmentation (diaPASEF) technology.

Results

A total of 470 and 726 proteins were quantified in S-sEVs and 1801 and 1834 proteins in L-sEVs from FR and LS boars, respectively. Differentially expressed sEV proteins (log2fold change ≥±1, p ≤ 0.05 and effect size d of Cohen >2.0) were found between the fertility groups: seven in S-sEVs and 52 in L-sEVs between H-FR and L-FR boars, and 47 in S-sEVs and 52 in L-sEVs between L-LS and S-LS boars. Many of these differentially expressed sEV proteins are involved in reproductive processes, particularly in sperm function and sperm-zona pellucida binding, but also in embryo development and implantation.

Conclusions

The sEV proteome differs between more and less fertile boars, with many of the differentially expressed proteins known as involved in reproductive processes. This would suggest that sEVs may be involved in male fertility and that some of the differentially expressed sEV proteins could be potential fertility markers for AI boars.

背景:预测农场动物的雄性生育能力仍然是一个挑战。精浆(SP)中含有大量异质性的精胞外囊泡(sev),被认为与生殖过程有关,可能是理解男性生育能力的关键。目的:鉴定高育性公猪和低育性公猪之间差异表达的sEV蛋白,并将其作为人工授精(AI)计划中公猪育性生物标志物的候选物。材料和方法:从育性不同的AI公猪SP样本中提取小(S)和大(L) sEV亚群:高(H)或低(L)产仔率(FR)和大(L)或小(S)产仔数(LS)。S-和L-sEV亚群通过大小排斥色谱分离,并根据细胞外囊泡研究的最小信息(MISEV2023)指南进行表征。蛋白质组学分析(每个生育组和sEV亚组三个生物重复)使用Bruker timsTOF fleX™仪器进行,该仪器具有数据独立采集并行积累-序列碎片化(diaPASEF)技术。结果:从FR和LS公猪的s - sev中分别定量到470和726个蛋白,从l - sev中分别定量到1801和1834个蛋白。sEV蛋白差异表达(log2倍变化≥±1,p≤0.05,Cohen bbb2.0效应值d): H-FR和L-FR公猪s -sEV中有7个,l -sEV中有52个;L-LS和S-LS公猪s -sEV中有47个,l -sEV中有52个。许多这些差异表达的sEV蛋白参与生殖过程,特别是精子功能和精子-透明带结合,但也参与胚胎发育和着床。结论:sEV蛋白质组在可育性较高和较低的公猪之间存在差异,其中许多差异表达的蛋白质被认为与生殖过程有关。这表明sEV可能与雄性繁殖有关,一些差异表达的sEV蛋白可能是AI公猪潜在的生育标记。
{"title":"Proteomic profiling of porcine seminal extracellular vesicles reveals potential in vivo fertility biomarkers","authors":"Isabel Barranco,&nbsp;Pablo Martínez-Díaz,&nbsp;Ana Parra,&nbsp;María José Martínez-Alborcia,&nbsp;Xiomara Lucas,&nbsp;Heriberto Rodríguez-Martínez,&nbsp;Jordi Roca","doi":"10.1111/andr.70089","DOIUrl":"10.1111/andr.70089","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Predicting male fertility in farm animals remains a challenge. Seminal plasma (SP) contains a high amount of heterogeneous seminal extracellular vesicles (sEVs), believed involved in reproductive processes and maybe key to understanding male fertility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To identify the sEV proteins that are differentially expressed between more and less fertile boars and that could be candidates for fertility biomarkers in boars used in artificial insemination (AI) programs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and methods</h3>\u0000 \u0000 <p>Small (S) and large (L) sEV subsets from SP samples of AI boars with differences in fertility: high (H) or low (L) farrowing rate (FR) and large (L) or small (S) litter size (LS). The S- and L-sEV subsets were isolated by size exclusion chromatography and characterized according to the Minimal Information for Studies of Extracellular Vesicles (MISEV2023) guidelines. Proteomic analyses (three biological replicates per fertility group and sEV subset) were performed using a Bruker timsTOF fleX™ instrument with data-independent acquisition parallel accumulation-serial fragmentation (diaPASEF) technology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 470 and 726 proteins were quantified in S-sEVs and 1801 and 1834 proteins in L-sEVs from FR and LS boars, respectively. Differentially expressed sEV proteins (log<sub>2</sub>fold change ≥±1, <i>p</i> ≤ 0.05 and effect size <i>d</i> of Cohen &gt;2.0) were found between the fertility groups: seven in S-sEVs and 52 in L-sEVs between H-FR and L-FR boars, and 47 in S-sEVs and 52 in L-sEVs between L-LS and S-LS boars. Many of these differentially expressed sEV proteins are involved in reproductive processes, particularly in sperm function and sperm-zona pellucida binding, but also in embryo development and implantation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The sEV proteome differs between more and less fertile boars, with many of the differentially expressed proteins known as involved in reproductive processes. This would suggest that sEVs may be involved in male fertility and that some of the differentially expressed sEV proteins could be potential fertility markers for AI boars.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"14 2","pages":"555-570"},"PeriodicalIF":3.4,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/andr.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558873","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}
引用次数: 0
The educational level impact on treatment adherence in PDE5i-naïve men with erectile dysfunction: A real-life cross-sectional study. 教育水平对PDE5i-naïve男性勃起功能障碍患者治疗依从性的影响:一项真实横断面研究。
IF 3.2 2区 医学 Q1 ANDROLOGY Pub Date : 2025-07-02 DOI: 10.1111/andr.70092
Gabriele Birolini, Alessandro Bertini, Edoardo Pozzi, Massimiliano Raffo, Fausto Negri, Christian Corsini, Federico Belladelli, Alessia d'Arma, Luca Boeri, Francesco Montorsi, Andrea Salonia

Introduction: The impact of the educational level on the adherence to phosphodiesterase type 5 inhibitors (PDE5i) among men with erectile dysfunction (ED) remains understudied. We aimed to investigate how the educational level influences patient's compliance to newly prescribed PDE5i in men with ED who had never previously used this class of drugs.

Materials and methods: Complete data from 1264 consecutive PDE5i naive men presenting with new onset ED were retrospectively analyzed. Patients were grouped according to their educational level into low (elementary and/or secondary school education), mid (high school), and high (university degrees) educational levels. Baseline health significant comorbidities were scored with the Charlson comorbidity index (CCI). All patients completed the International Index of Erectile Function (IIEF) and the Beck depression inventory questionnaires at baseline. PDE5i were prescribed to all patients. Kaplan-Meier (KM) curves estimated the discontinuation free-survival (DFS) after stratification according to the educational level. Multivariable (MVA) Cox regression addressed the association between the educational level and PDE5is' discontinuation.

Results: Of all, 160 (13%), 573 (45%), and 531 (42%) individuals depicted low, mid, and high educational level, respectively. Median (IQR) age and follow-up time were 51 (39-61) and 8.5 (5.9-11.3) years, respectively. Patients with higher educational level were more likely to be younger (49 vs. 56 years, p < 0.001), reporting lower BMI values (25 vs. 26.3 kg/m2, p < 0.001) and lower rates of CCI ≥ 1 (17% vs. 27%, p = 0.009), compared to their lower educational level counterparts. No significant differences were found in terms of duration of PDE5is assumption and IIEF-erectile function (IIEF-EF) across the groups. Kaplan-Meier survival analyses, stratified by the educational level, revealed significantly different patterns of PDE5i discontinuation-free survival across educational levels (log-rank test, p = 0.028). At multivariable Cox regression analysis, higher educational levels were significantly associated with PDE5i discontinuation, even after adjusting for age at presentation, IIEF-EF score, and relationship status simultaneously.

Conclusions: Current findings demonstrated that the higher the educational level, the greater the PDE5is discontinuation rate in men with ED. These results highlight a particular aspect of patients' compliance with PDE5is, enabling improvements in real-life pharmacological management for ED.

导读:教育水平对勃起功能障碍(ED)男性坚持使用磷酸二酯酶5型抑制剂(PDE5i)的影响仍未得到充分研究。我们的目的是研究教育水平如何影响以前从未使用过这类药物的ED患者对新处方PDE5i的依从性。材料和方法:回顾性分析1264例PDE5i新发ED的男性患者的完整资料。患者根据受教育程度分为低(小学和/或中学)、中(高中)和高(大学)教育程度。基线健康显著合并症用Charlson合并症指数(CCI)评分。所有患者在基线时完成国际勃起功能指数(IIEF)和贝克抑郁量表问卷。所有患者均使用PDE5i。Kaplan-Meier (KM)曲线根据受教育程度估计分层后的终止自由生存(DFS)。多变量(MVA) Cox回归分析了教育水平与PDE5is停药之间的关系。结果:160人(13%)、573人(45%)和531人(42%)分别表现为低、中、高等教育水平。中位(IQR)年龄为51(39-61)岁,随访时间为8.5(5.9-11.3)岁。结论:目前的研究结果表明,受教育程度越高,ED男性患者PDE5is停药率越高。这些结果突出了患者对PDE5is依从性的一个特定方面,从而改善了ED的现实药理管理。
{"title":"The educational level impact on treatment adherence in PDE5i-naïve men with erectile dysfunction: A real-life cross-sectional study.","authors":"Gabriele Birolini, Alessandro Bertini, Edoardo Pozzi, Massimiliano Raffo, Fausto Negri, Christian Corsini, Federico Belladelli, Alessia d'Arma, Luca Boeri, Francesco Montorsi, Andrea Salonia","doi":"10.1111/andr.70092","DOIUrl":"https://doi.org/10.1111/andr.70092","url":null,"abstract":"<p><strong>Introduction: </strong>The impact of the educational level on the adherence to phosphodiesterase type 5 inhibitors (PDE5i) among men with erectile dysfunction (ED) remains understudied. We aimed to investigate how the educational level influences patient's compliance to newly prescribed PDE5i in men with ED who had never previously used this class of drugs.</p><p><strong>Materials and methods: </strong>Complete data from 1264 consecutive PDE5i naive men presenting with new onset ED were retrospectively analyzed. Patients were grouped according to their educational level into low (elementary and/or secondary school education), mid (high school), and high (university degrees) educational levels. Baseline health significant comorbidities were scored with the Charlson comorbidity index (CCI). All patients completed the International Index of Erectile Function (IIEF) and the Beck depression inventory questionnaires at baseline. PDE5i were prescribed to all patients. Kaplan-Meier (KM) curves estimated the discontinuation free-survival (DFS) after stratification according to the educational level. Multivariable (MVA) Cox regression addressed the association between the educational level and PDE5is' discontinuation.</p><p><strong>Results: </strong>Of all, 160 (13%), 573 (45%), and 531 (42%) individuals depicted low, mid, and high educational level, respectively. Median (IQR) age and follow-up time were 51 (39-61) and 8.5 (5.9-11.3) years, respectively. Patients with higher educational level were more likely to be younger (49 vs. 56 years, p < 0.001), reporting lower BMI values (25 vs. 26.3 kg/m<sup>2</sup>, p < 0.001) and lower rates of CCI ≥ 1 (17% vs. 27%, p = 0.009), compared to their lower educational level counterparts. No significant differences were found in terms of duration of PDE5is assumption and IIEF-erectile function (IIEF-EF) across the groups. Kaplan-Meier survival analyses, stratified by the educational level, revealed significantly different patterns of PDE5i discontinuation-free survival across educational levels (log-rank test, p = 0.028). At multivariable Cox regression analysis, higher educational levels were significantly associated with PDE5i discontinuation, even after adjusting for age at presentation, IIEF-EF score, and relationship status simultaneously.</p><p><strong>Conclusions: </strong>Current findings demonstrated that the higher the educational level, the greater the PDE5is discontinuation rate in men with ED. These results highlight a particular aspect of patients' compliance with PDE5is, enabling improvements in real-life pharmacological management for ED.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537808","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}
引用次数: 0
Ubiquitin-mediated immunoglobulin-binding protein 1 degradation promotes autophagy and sperm capacitation in vitro 泛素介导的免疫球蛋白结合蛋白1降解促进体外自噬和精子获能。
IF 3.4 2区 医学 Q1 ANDROLOGY Pub Date : 2025-07-02 DOI: 10.1111/andr.70093
Xinglin Qu, Yanqiu Lv, Yuyang Zhang, Lipeng Cao, Junzheng Zhang, Xuan Chen, Yi Jin

Background

During sperm capacitation, post-translational modifications such as SUMOylation are crucial for maintaining protein homeostasis. Macroautophagy (autophagy) is essential for cellular and energy homeostasis, aiding in the survival of reproductive cells and protecting against ovarian aging. However, the role of autophagy in capacitated sperm remains unclear.

Objectives

This study aimed to explore the relationship between small ubiquitin-like modifier 1 (SUMO1)-modified proteins and autophagy during sperm capacitation, focusing on the involvement of immunoglobulin-binding protein 1 (IGBP1) in the autophagy pathway.

Materials and methods

Tandem mass spectrometry was employed to identify SUMO1-modified proteins in boar sperm before and after capacitation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted to investigate the involvement of these proteins in autophagy, specifically examining the modification and degradation of IGBP1 via the ubiquitin-proteasome pathway (UPP). The regulatory role of the PKA-mTOR signaling axis on autophagy during capacitation was also examined.

Results

A total of 229 SUMO1-modified proteins were identified in the non-capacitated group and 197 in the capacitated group, with 77 proteins unique to the non-capacitated state and 45 unique to the capacitated state. IGBP1 was found to be involved in the autophagy pathway, and its SUMO1 modification level significantly decreased after sperm capacitation, leading to its degradation via UPP. This degradation promoted autophagy and increased mTOR activity. The autophagy process involving IGBP1 was regulated by the upstream PKA-mTOR signaling axis. Additionally, a negative correlation between autophagy and apoptosis was observed during sperm capacitation, where the activation of autophagy enhanced capacitation and improved sperm–egg binding and embryonic development.

Conclusion

The degradation of de-SUMOylated IGBP1 via UPP promotes sperm autophagy and enhances in vitro capacitation, providing new insights into the molecular mechanisms of sperm capacitation.

背景:在精子获能过程中,翻译后修饰如SUMOylation对维持蛋白质稳态至关重要。巨噬(自噬)对细胞和能量稳态至关重要,有助于生殖细胞的存活和防止卵巢衰老。然而,自噬在失能精子中的作用尚不清楚。目的:本研究旨在探讨精子获能过程中小泛素样修饰物1 (SUMO1)修饰蛋白与自噬的关系,重点研究免疫球蛋白结合蛋白1 (IGBP1)在自噬通路中的作用。材料与方法:采用串联质谱法对猪精子获能前后的sumo1修饰蛋白进行鉴定。京都基因与基因组百科(KEGG)通路分析研究了这些蛋白在自噬中的作用,特别是通过泛素-蛋白酶体通路(UPP)检测了IGBP1的修饰和降解。我们还研究了PKA-mTOR信号轴在获能过程中对自噬的调节作用。结果:在失能组和失能组共鉴定出229个sumo1修饰蛋白,其中77个蛋白为非失能状态所特有,45个为失能状态所特有。IGBP1参与自噬途径,其SUMO1修饰水平在精子获能后显著降低,导致其通过UPP降解。这种降解促进了自噬并增加了mTOR活性。IGBP1参与的自噬过程受上游PKA-mTOR信号轴调控。此外,在精子获能过程中观察到自噬和凋亡之间的负相关,其中自噬的激活增强了获能并改善了精子-卵子结合和胚胎发育。结论:通过UPP降解去sumoylated IGBP1可促进精子自噬并增强体外获能,为精子获能的分子机制提供了新的认识。
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引用次数: 0
Maternal, childhood and adolescent influences on Leydig cell functional capacity and circulating INSL3 concentration in young adults: Importance of childhood infections and body mass index. 母亲、儿童和青少年对青少年间质细胞功能能力和循环INSL3浓度的影响:儿童感染和体重指数的重要性
IF 3.2 2区 医学 Q1 ANDROLOGY Pub Date : 2025-07-02 DOI: 10.1111/andr.70091
Richard Ivell, Bilal Tilumcu, Waleed Alhujaili, Ravinder Anand-Ivell

Background: The constitutive Leydig cell hormone insulin-like peptide 3 (INSL3) is considered a good estimate of the adult Leydig cell functional capacity and appears to remain relatively consistent throughout adult male life, only gradually declining into old age. Importantly, in younger men it appears to predict hypogonadism and hence later health and morbidity.

Objectives: Here, we have used the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort of boys and young men to assess those factors during pregnancy, infancy, childhood, and adolescence, when the adult-type Leydig cell population is being established, which by association might influence the final circulating INSL3 concentration in young adulthood.

Methods: A wide range of clinical, anthropometric and lifestyle parameters were assessed from up to 2000 boys and young men based on direct medical measurement and/or by targeted questionnaires. Scalar variables used bivariate correlation analysis, whereas comparative statistics, such as t-tests, were applied to categorical variables.

Results: Maternal parameters, such as maternal smoking, gestational age, or being small for gestational age (SGA) appeared to have no association with adult INSL3 levels. Of all the parameters assessed, those with greatest impact on young adult Leydig cell status appeared to be childhood and adolescent body mass index (BMI) and early childhood infectious disease. Particularly, chickenpox in infancy had a marked and significant negative association with INSL3 (reduced by 10%-14%) at both 17 and 24 years. Being overweight (> 85th percentile) at 13 years was associated with a 20% reduction in young adult INSL3. In contrast, childhood and adolescent inflammatory factors and cigarette exposure appeared to have no long-lasting impact on adult Leydig cell status.

Limitations: This retrospective cohort study is limited by relatively small numbers and by its correlative analysis. The hypotheses generated will need to be validated in more extensive, in-depth studies.

Lay summary: The testis hormone INSL3 is considered a good estimate of the gonadal capacity to make testosterone. It is relatively constant throughout adult male life, only gradually declining into old age. Importantly, in younger men reduced INSL3 appears to predict hypogonadism and hence later health and morbidity. Whilst showing low within-individual variation, between individuals INSL3 can vary more than 10- up to 100-fold. The source of this variance is unknown but is believed to have its origin during childhood and adolescence. Analysis of data from the ALSPAC cohort implies that of various parameters assessed, only childhood and adolescent BMI as well as early infectious disease, in particular chickenpox, have any influence on young adult INSL3 concentration, respectively reducing circulating levels each by

背景:构成间质细胞激素胰岛素样肽3 (INSL3)被认为是对成年间质细胞功能能力的一个很好的估计,并且在成年男性的一生中似乎保持相对一致,只是在老年时逐渐下降。重要的是,在年轻男性中,它似乎可以预测性腺功能减退,从而预测以后的健康和发病率。目的:在这里,我们使用了雅芳父母和儿童纵向研究(ALSPAC)的男孩和年轻男性队列来评估怀孕、婴儿期、儿童期和青春期的这些因素,当成人型间质细胞群正在建立时,这些因素可能会影响青年期最终的循环INSL3浓度。方法:根据直接医学测量和/或有针对性的问卷调查,对多达2000名男孩和年轻男性进行了广泛的临床、人体测量和生活方式参数评估。标量变量使用双变量相关分析,而比较统计,如t检验,应用于分类变量。结果:母体参数,如母体吸烟、胎龄或小于胎龄(SGA)似乎与成人INSL3水平无关。在所有评估的参数中,对青少年间质细胞状态影响最大的似乎是儿童和青少年体重指数(BMI)和儿童早期传染病。特别是,婴儿期水痘与17岁和24岁时的INSL3有显著的负相关(减少10%-14%)。13岁时超重(bbb85百分位数)与年轻人INSL3减少20%相关。相比之下,儿童和青少年的炎症因子和吸烟暴露似乎对成年间质细胞状态没有长期影响。局限性:本回顾性队列研究数量较少,且相关分析存在局限性。所产生的假设需要在更广泛、更深入的研究中得到验证。摘要:睾丸激素INSL3被认为是对性腺分泌睾酮能力的一个很好的估计。在成年男性的一生中,它是相对恒定的,只是在老年时逐渐下降。重要的是,在年轻男性中,INSL3的降低似乎预示着性腺功能减退,从而预示着后期的健康和发病率。虽然在个体内表现出较低的差异,但在个体之间,INSL3的差异可以超过10倍至100倍。这种差异的来源尚不清楚,但据信它起源于童年和青春期。对ALSPAC队列数据的分析表明,在评估的各种参数中,只有儿童和青少年BMI以及早期传染病,特别是水痘,对年轻人的INSL3浓度有任何影响,分别使循环水平降低10%-20%。需要更多的研究来了解这些因素如何影响睾丸功能的机制,可以采取哪些缓解措施,以及可能涉及哪些其他因素。
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引用次数: 0
Epidemiology of hypospadias in China: A nationwide surveillance-based study, 2010-2020. 2010-2020年中国尿道下裂流行病学研究
IF 3.2 2区 医学 Q1 ANDROLOGY Pub Date : 2025-06-28 DOI: 10.1111/andr.70090
Chen Zhiyu, Gao Yuyang, Xu Wenli, Li Wenyan, Liu Zhen, Zhou Jiayuan, Zhu Jun, Dai Li

Background: The prevalence of hypospadias varied internationally. However, epidemiological data on hypospadias in contemporary China remain limited.

Objectives: We aim to examine the epidemiological characteristics of hypospadias in Chinese population.

Materials and methods: We performed a prevalence analysis using data from the Chinese Birth Defects Monitoring Network from 2010 to 2020. We analyzed the prevalence of overall, isolated, and associated hypospadias by birth year, maternal age, maternal residence, and geographic region. We used Poisson regression with adjusted prevalence rate ratios for assessing the impact of demographic characteristics and Joinpoint regression for analyzing temporal trends.

Results: A total of 11,782 hypospadias cases were identified among 11,575,036 male births with a prevalence of 10.18 per 10,000 male births. Of these, 9700 (82.3%) were isolated and 2082 (17.7%) were associated hypospadias. Of these cases, 639 (5.4%) were classified as anterior hypospadias, 1052 (8.9%) as middle hypospadias, 413 (3.5%) as proximal hypospadias, and 9678 (82.1%) as unspecified hypospadias, based on their severity. The prevalence of overall, isolated, and associated hypospadias increased significantly over the study period. Prevalence also varied significantly by maternal residence, maternal age, and geographical region. Infants with associated hypospadias experienced a significant higher risk of perinatal death. The most frequent associated anomalies involved the cardiovascular, genitourinary, and musculoskeletal systems.

Discussion and conclusion: This study provides contemporary national data on the epidemiology of hypospadias in China. The observed increasing prevalence and variations by severity underscore the need for further etiological, epidemiological, and clinical research.

背景:尿道下裂的患病率在国际上各不相同。然而,当代中国尿道下裂的流行病学资料仍然有限。目的:探讨中国人群尿道下裂的流行病学特征。材料和方法:我们使用2010年至2020年中国出生缺陷监测网络的数据进行了患病率分析。我们根据出生年份、母亲年龄、母亲居住地和地理区域分析了整体、孤立和相关尿道下裂的患病率。我们使用泊松回归与调整患病率比率来评估人口统计学特征的影响,并使用连接点回归来分析时间趋势。结果:在11,575,036例男婴中,共发现11,782例尿道下裂病例,患病率为10.18 / 10,000。其中9700例(82.3%)为孤立性,2082例(17.7%)为伴尿道下裂。在这些病例中,根据严重程度,639例(5.4%)为前尿道下裂,1052例(8.9%)为中尿道下裂,413例(3.5%)为近端尿道下裂,9678例(82.1%)为未明确的尿道下裂。总体、孤立性和相关尿道下裂的患病率在研究期间显著增加。患病率也因产妇居住地、产妇年龄和地理区域而有显著差异。伴有尿道下裂的婴儿围产期死亡风险显著增高。最常见的相关异常包括心血管、泌尿生殖系统和肌肉骨骼系统。讨论与结论:本研究提供了中国尿道下裂流行病学的当代国家数据。观察到的患病率增加和严重程度的变化强调了进一步进行病因学、流行病学和临床研究的必要性。
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