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Relaxin-2 improves type I diabetes mellitus-induced erectile dysfunction in rats by protecting cavernous endothelial and smooth muscle function, and inhibiting penile fibrosis and apoptosis. 松弛素-2能保护海绵体内皮和平滑肌功能,抑制阴茎纤维化和细胞凋亡,从而改善I型糖尿病诱发的大鼠勃起功能障碍。
IF 3.2 2区 医学 Q1 ANDROLOGY Pub Date : 2024-12-09 DOI: 10.1111/andr.13822
Bocheng Tu, Kang Liu, Bo Wen, Peng Hu, Taotao Sun, Beining Li, Manan Sulaiman, Shujun Jiang, Tao Wang, Jihong Liu, Yang Luan

Background: Diabetes mellitus-induced erectile dysfunction (DMED) responds poorly to first-line treatments, necessitating the development of new therapeutic strategies. Relaxin-2 (RLX-2) plays a crucial role in protecting vascular endothelium, vasodilatation, and antifibrosis in various diseases. However, its effects and mechanisms on DMED remain unclear.

Objectives: To investigate the effects and mechanisms of RLX-2 on DMED rats in vivo and vitro.

Methods: For in vivo research, 30 Sprague-Dawley rats were allocated into three groups: control, DMED, and DMED + RLX-2. The induction of DMED in the rats was achieved through intraperitoneal administration of streptozotocin, with confirmation of ED status being conducted via the apomorphine test. Rats in the DMED + RLX-2 group received continuous RLX-2 treatment by osmotic pump. Following a 4-week treatment period, assessment of erectile function was carried out using cavernous manometry, and samples of corpus cavernosum tissues were procured for subsequent analysis. For in vitro research, human cardiac microvascular endothelial cells (HCMECs) were allocated into three groups: control, high glucose (HG, 40 mM), and HG + RLX-2. HCMECs were cultured for 6 days and treated with RLX-2 for 48 h before collection for subsequent experiments.

Results: In DMED rats, RLX-2 treatment partially improved erectile function. We observed relatively normalized functions of endothelial and smooth muscle cells with decreased levels of apoptosis and fibrosis in the penis. In vitro experiments also demonstrated the antihyperglycemic effects of RLX-2.

Conclusions: RLX-2 can protect endothelial and smooth muscle function, and inhibit aberrant apoptosis and fibrosis in the corpus cavernosum, thereby improving erectile function in DMED rats. This may provide a novel treatment for DMED.

背景:糖尿病性勃起功能障碍(DMED)对一线治疗效果不佳,需要开发新的治疗策略。松弛素-2 (RLX-2)在多种疾病中起着保护血管内皮、血管舒张和抗纤维化的重要作用。然而,其对DMED的影响和机制尚不清楚。目的:探讨RLX-2对DMED大鼠体内外的作用及其机制。方法:将30只Sprague-Dawley大鼠分为对照组、DMED组和DMED + RLX-2组进行体内实验。通过腹腔注射链脲佐菌素诱导大鼠DMED,并通过阿波啡试验确认ED状态。DMED + RLX-2组大鼠连续给予渗透泵RLX-2治疗。在4周的治疗期后,使用海绵体测压法评估勃起功能,并获取海绵体组织样本进行后续分析。体外研究将人心脏微血管内皮细胞(HCMECs)分为对照组、高糖组(HG, 40 mM)和HG + RLX-2组。hcmec培养6 d, RLX-2处理48 h,收集后进行后续实验。结果:在DMED大鼠中,RLX-2治疗可部分改善勃起功能。我们观察到阴茎内皮细胞和平滑肌细胞的功能相对正常化,细胞凋亡和纤维化水平下降。体外实验也证实了RLX-2的降糖作用。结论:RLX-2可保护DMED大鼠内皮和平滑肌功能,抑制海绵体异常凋亡和纤维化,从而改善勃起功能。这可能为DMED提供一种新的治疗方法。
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引用次数: 0
G protein-coupled receptor-receptor interactions in gonadal physiology. 性腺生理中G蛋白偶联受体-受体相互作用。
IF 3.2 2区 医学 Q1 ANDROLOGY Pub Date : 2024-12-09 DOI: 10.1111/andr.13821
Clara Lazzaretti, Mohammed Akli Ayoub, Livio Casarini

Background: Gonadotropins are glycoprotein hormones fundamental in the endocrine regulation of reproduction. They act on structurally similar members of G protein-coupled receptors (GPCRs) expressed exclusively in the gonads and support gametogenesis, sex steroid synthesis, and pregnancy. While it is a common opinion that the gonadotropin receptors act as a single molecule entity (monomer), increasing evidence underlines the formation of molecular complexes involving multiple receptors.

Objectives: To review current knowledge of membrane receptor-receptor interactions in reproduction.

Results and discussion: Homo/heteromers of gonadotropin receptors may act as allosteric modulators, act as biased agonist and/or cooperate in sustaining intracellular signals fundamental to support reproduction. Technical limitations lead to in vitro data that require to be confirmed in vivo to figure out the physiological impact of gonadotropin receptor assemblies.

Conclusions: Gonadotropin receptor homo/heteromers provide a new field of research that deserves attention for possible clinical and therapeutic implications in physiology and pathophysiology.

背景:促性腺激素是在生殖内分泌调节中起重要作用的糖蛋白激素。它们作用于仅在性腺中表达的G蛋白偶联受体(gpcr)的结构相似的成员,并支持配子发生、性类固醇合成和怀孕。虽然人们普遍认为促性腺激素受体是一个单分子实体(单体),但越来越多的证据强调了涉及多个受体的分子复合物的形成。目的:综述生殖过程中膜受体-受体相互作用的最新研究进展。结果和讨论:促性腺激素受体的同性/异构体可能作为变构调节剂,作为偏向激动剂和/或合作维持细胞内信号,支持生殖的基础。技术限制导致体外数据需要在体内确认,以确定促性腺激素受体组装的生理影响。结论:促性腺激素受体同/异异体是一个值得关注的新研究领域,在生理和病理生理方面可能具有临床和治疗意义。
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引用次数: 0
The sitting men: A systematic review of spare and working time exposure to sedentariness in relation to semen parameters. 坐着的人:一项关于空闲时间和工作时间暴露于久坐与精液参数关系的系统综述。
IF 3.2 2区 医学 Q1 ANDROLOGY Pub Date : 2024-12-08 DOI: 10.1111/andr.13816
Vittoria Sterpi, Elena Ricci, Francesca Chiaffarino, Francesco Fedele, Giovanna Esposito, Fabio Parazzini, Paola Viganò, Sonia Cipriani

Background: Over the past few decades, several studies have found that semen quality parameters have steadily declined over time. Many hypotheses have been made to explain this finding, among which a sedentary lifestyle has been investigated. To synthesize the current evidence, we performed a systematic review of published papers reporting on the relationship between sedentary habits and semen parameters.

Methods: Embase and PubMed were systematically searched for papers published in English up to May 2023. We included all full-text observational papers that reported the relationship between sedentariness and semen parameters. Article selection adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.

Results: Sixteen observational studies were ultimately included, six in healthy men and ten in men from Fertility Clinics. They encompassed a total of 13,509 men, with 9877 being healthy men and 3632 presenting at Fertility Clinics for initial assessment. In terms of semen volume, no association emerged in the six studies involving healthy men: however, results in men referring to fertility clinics mainly showed no association, with one indicating a decline and one higher volume. Twelve studies did not report differences in sperm concentration, while one study in men from Fertility Clinics and two in healthy men observed a decline in this parameter with increasing time spent on TV watching or sedentary posture in spare time. Total sperm count was found to be similar across groups of inactivity, except for one study that showed a significant decrease when men from Fertility Clinics spent more time watching TV. No significant differences were reported in sperm motility across all studies, with only one study, among those addressing sperm morphology, indicating a lower percentage of normal forms in men watching TV more than 3 h per day. Finally, three studies conducted in men referring to Fertility Clinics analyzed the sperm DNA fragmentation index. Two of these studies found a higher DNA fragmentation index in men spending more time per day in a sitting posture.

Conclusions: This review suggests a weak association between time spent sitting during spare time and sperm concentration, but the findings are inconsistent, highlighting the need for further research.

背景:在过去的几十年里,一些研究发现精液质量参数随着时间的推移稳步下降。人们提出了许多假设来解释这一发现,其中包括久坐不动的生活方式。为了综合目前的证据,我们对已发表的关于久坐习惯与精液参数之间关系的论文进行了系统回顾。方法:系统检索Embase和PubMed截至2023年5月发表的英文论文。我们纳入了所有报道久坐与精液参数之间关系的全文观察性论文。文章选择遵循系统评价和荟萃分析(PRISMA)指南的首选报告项目。结果:最终纳入了16项观察性研究,其中6项针对健康男性,10项针对来自生育诊所的男性。他们共包括13,509名男性,其中9877名是健康男性,3632名在生育诊所进行初步评估。就精液量而言,涉及健康男性的六项研究中没有发现任何关联:然而,前往生育诊所的男性的结果主要显示没有关联,一项研究表明精液量下降,一项研究表明精液量增加。12项研究没有报告精子浓度的差异,而一项针对生育诊所的男性的研究和两项针对健康男性的研究发现,随着看电视时间的增加或业余时间久坐不动,精子浓度会下降。除了一项研究表明,当来自生育诊所的男性花更多时间看电视时,精子总数会显著减少外,其他不运动的人群的精子总数相似。在所有的研究中,精子活力没有明显的差异,只有一项研究表明,在那些研究精子形态的研究中,每天看电视超过3小时的男性正常精子的比例较低。最后,参考生育诊所在男性中进行的三项研究分析了精子DNA碎片指数。其中两项研究发现,每天久坐的男性DNA断裂指数更高。结论:这篇综述表明,业余时间坐着的时间与精子浓度之间存在微弱关联,但研究结果并不一致,需要进一步研究。
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引用次数: 0
Congenital absence of vas deferens: Anatomical and embryological inputs from a series of autopsies reported in Europe throughout the 18th and 19th century. 先天性输精管缺失:18世纪和19世纪欧洲一系列尸检报告的解剖学和胚胎学输入。
IF 3.2 2区 医学 Q1 ANDROLOGY Pub Date : 2024-12-08 DOI: 10.1111/andr.13815
Marion Bendayan, Florence Boitrelle, Safouane Maurens-Hamdi

Congenital absence of the vas deferens (CAVD) is a syndrome with a heterogeneous presentation: bilateral (CBAVD) or unilateral (CUAVD), complete or partial and associated or not with other anomalies of the male urogenital system. A turning point came in 1968 when CBAVD was associated with cystic fibrosis and its CFTR gene mutations. Genetic studies then revealed that a minority of CBAVD but a majority of CUAVD are CFTR-independent. In the literature, reference is classically made to two sources from the 18th and 19th century: Hunter and Reverdin. This scarcity prompted us to look for additional observations of CAVD. By a meticulous bibliographical search, we identified a corpus of 10 European observations (8 CUAVD and 2 CBAVD) some of them richly illustrated. They were collected between 1755 and 1876 throughout adult men autopsies. We also provided their primary and unambiguous sources. Analysis of the reported data revealed some interesting facts: both CBAVD cases were unlikely linked to cystic fibrosis and half of CUAVD cases were associated with an ipsilateral kidney absence, suggesting a CFTR-independent pathophysiology. Moreover, the anatomical details of the anomalies raise interesting embryological questions we have tried to address in the light of current data. This work made it possible to identify new historical sources dealing with male genital tract pathologies. It sheds light on the origins of andrology and opens up interesting prospects for research and education in the field.

先天性输精管缺失(CAVD)是一种表现多样的综合征:双侧(CBAVD)或单侧(CUAVD),完全或部分,与男性泌尿生殖系统的其他异常相关或不相关。转折点出现在1968年,当时cavd与囊性纤维化及其CFTR基因突变有关。遗传研究随后显示,少数cavd和大多数CUAVD与cftr无关。在文献中,经典地引用了18世纪和19世纪的两个来源:亨特和雷维丁。这种稀缺性促使我们寻找对CAVD的额外观察。通过细致的文献检索,我们确定了10个欧洲观测的语料库(8个CUAVD和2个cavd),其中一些插图丰富。它们是在1755年至1876年间从成年男性尸体解剖中收集的。我们还提供了他们的主要和明确的来源。对报告数据的分析揭示了一些有趣的事实:两例cavd病例都不太可能与囊性纤维化有关,一半的CUAVD病例与同侧肾脏缺失有关,提示cfr独立的病理生理。此外,这些异常的解剖细节提出了有趣的胚胎学问题,我们试图根据目前的数据来解决。这项工作使得有可能确定新的历史来源处理男性生殖道病理。它揭示了男科学的起源,并为该领域的研究和教育开辟了有趣的前景。
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引用次数: 0
Evaluation of dimethandrolone undecanoate in non-human primates as a candidate for long-acting injectable male contraceptive. 十一酸地美雄龙在非人灵长类动物中作为长效注射男性避孕药的候选物的评价。
IF 3.2 2区 医学 Q1 ANDROLOGY Pub Date : 2024-12-08 DOI: 10.1111/andr.13819
Deborah I Bunin, Kyuri Kim, Toufan Parman, Janet Gahagen, Mary B Zelinski, Tiffany Adevai, Christina Wang, Liang Tang, Lalitha Iyer, Aaron Endsley, Diana L Blithe, Min S Lee

Background: Dimethandrolone undecanoate (DMAU) is under development as a single agent hormonal male contraceptive. DMAU is a prodrug hydrolyzed by esterase(s) to the active metabolite dimethandrolone (DMA) which has dual androgenic and progestogenic actions. Phase 1 clinical trial results show DMAU to be well-tolerated as an oral contraceptive in healthy men; however, delivery of DMAU as a long-acting injectable rather than a daily oral formulation would provide user compliance benefits and address oral bioavailability concerns.

Objective: To assess the safety, pharmacokinetics (PK), and long-acting contraceptive potential of DMAU in male non-human primates (NHP) when delivered as an injectable or oral formulation.

Materials and methods: DMAU was administered to cynomolgus macaques orally for 9 months or as five weekly intramuscular (IM) injections and to rhesus macaques as a single IM injection. Evaluations of safety, fertility indicators, and serum levels of DMAU and DMA were followed > 2 years post-dose.

Results: Repeat dose oral and IM administrations were well-tolerated with no significant toxicological findings. Dramatic reductions in serum testosterone concentration occurred within days of administration followed by sustained suppression of additional fertility indicators (e.g., serum inhibin B, sperm count, and testicular spermatogenesis). Slight body weight increases and reductions in testes weight also occurred. Repeat DMAU injections resulted in DMA serum concentrations above the lower limit of quantification (1 ng/mL) for > 500 days. DMAU PK parameters increased with increasing IM dose, while dose dependence was not seen for serum DMA concentrations suggesting a depot effect with a reservoir of non-circulating prodrug remaining at the injection site which gets slowly hydrolyzed to DMA and absorbed into circulation. Testosterone levels and spermatogenesis returned by the end of the recovery period.

Conclusions: Nonclinical safety, PK, and pharmacodynamic data in male NHP demonstrate the safe, well-tolerated, long-acting, and reversible contraceptive potential of injectable DMAU.

背景:十一酸地美雄龙(DMAU)作为一种单药激素男性避孕药正在开发中。DMAU是一种由酯酶水解成活性代谢物二美雄酮(DMA)的前药,具有雄激素和孕激素双重作用。1期临床试验结果显示,DMAU作为口服避孕药在健康男性中耐受性良好;然而,将DMAU作为长效注射剂而不是日常口服制剂,将为用户提供依从性益处,并解决口服生物利用度问题。目的:评价DMAU作为注射或口服制剂在雄性非人灵长类动物(NHP)体内的安全性、药代动力学(PK)和长效避孕潜力。材料与方法:食蟹猕猴连续9个月口服DMAU或每5周肌肉注射DMAU,恒河猕猴单次注射DMAU。在给药后2年随访安全性、生育指标和血清DMAU和DMA水平。结果:口服和IM的重复剂量耐受良好,没有明显的毒理学发现。在给药后的几天内,血清睾酮浓度急剧下降,随后持续抑制其他生育指标(如血清抑制素B、精子数量和睾丸精子发生)。体重轻微增加,睾丸重量也会减少。重复注射DMAU导致DMA血清浓度超过定量下限(1 ng/mL),持续50 ~ 500天。DMAU PK参数随着IM剂量的增加而增加,而血清DMA浓度没有剂量依赖性,提示注射部位保留非循环前药库的储存效应,这些前药被缓慢水解成DMA并被吸收到循环中。睾酮水平和精子生成在恢复期结束时恢复。结论:男性NHP的非临床安全性、PK和药效学数据表明,注射DMAU具有安全、耐受性好、长效和可逆的避孕潜力。
{"title":"Evaluation of dimethandrolone undecanoate in non-human primates as a candidate for long-acting injectable male contraceptive.","authors":"Deborah I Bunin, Kyuri Kim, Toufan Parman, Janet Gahagen, Mary B Zelinski, Tiffany Adevai, Christina Wang, Liang Tang, Lalitha Iyer, Aaron Endsley, Diana L Blithe, Min S Lee","doi":"10.1111/andr.13819","DOIUrl":"10.1111/andr.13819","url":null,"abstract":"<p><strong>Background: </strong>Dimethandrolone undecanoate (DMAU) is under development as a single agent hormonal male contraceptive. DMAU is a prodrug hydrolyzed by esterase(s) to the active metabolite dimethandrolone (DMA) which has dual androgenic and progestogenic actions. Phase 1 clinical trial results show DMAU to be well-tolerated as an oral contraceptive in healthy men; however, delivery of DMAU as a long-acting injectable rather than a daily oral formulation would provide user compliance benefits and address oral bioavailability concerns.</p><p><strong>Objective: </strong>To assess the safety, pharmacokinetics (PK), and long-acting contraceptive potential of DMAU in male non-human primates (NHP) when delivered as an injectable or oral formulation.</p><p><strong>Materials and methods: </strong>DMAU was administered to cynomolgus macaques orally for 9 months or as five weekly intramuscular (IM) injections and to rhesus macaques as a single IM injection. Evaluations of safety, fertility indicators, and serum levels of DMAU and DMA were followed > 2 years post-dose.</p><p><strong>Results: </strong>Repeat dose oral and IM administrations were well-tolerated with no significant toxicological findings. Dramatic reductions in serum testosterone concentration occurred within days of administration followed by sustained suppression of additional fertility indicators (e.g., serum inhibin B, sperm count, and testicular spermatogenesis). Slight body weight increases and reductions in testes weight also occurred. Repeat DMAU injections resulted in DMA serum concentrations above the lower limit of quantification (1 ng/mL) for > 500 days. DMAU PK parameters increased with increasing IM dose, while dose dependence was not seen for serum DMA concentrations suggesting a depot effect with a reservoir of non-circulating prodrug remaining at the injection site which gets slowly hydrolyzed to DMA and absorbed into circulation. Testosterone levels and spermatogenesis returned by the end of the recovery period.</p><p><strong>Conclusions: </strong>Nonclinical safety, PK, and pharmacodynamic data in male NHP demonstrate the safe, well-tolerated, long-acting, and reversible contraceptive potential of injectable DMAU.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794323","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
Prevalence of HPV infection in the general population of young and adult males in Italy. 意大利青年和成年男性一般人群中HPV感染的流行情况。
IF 3.2 2区 医学 Q1 ANDROLOGY Pub Date : 2024-12-03 DOI: 10.1111/andr.13817
Giuseppe Grande, Andrea Graziani, Luca De Toni, Federica Finocchi, Adriano Presciutti, Sara Corrò, Alberto Ferlin, Andrea Garolla

Background: The most prevalent sexually transmitted disease in the world has the human papillomavirus (HPV) as its etiological agent.

Objectives: To evaluate the prevalence of previous and actual HPV infection and the clinical manifestations in unselected males.

Materials and methods: A total of 718 males participating to a surveillance program were asked to complete a study visit at our unit, including semen collection, balanopreputial sulcus swab, and blood collection for total anti-HPV immunoglobulin G (IgG). When HPV-DNA was detected, we performed HPV fluorescence in situ hybridization, oral and anal swab, and penoscopy. Because previous studies demonstrated a very high risk for HPV infection in subjects with history of HPV-induced lesions, with a partner with diagnosed HPV infection or reporting couple infertility or sexual promiscuity and an increase of the risk in males having sex with males, in subjects with unprotected sexual intercourses or in heavy smokers, patients were therefore stratified according to the presence of these known risk factors (RFs).

Results: Actual HPV infection was detected in 401/718 subjects (55.85%). Oral HPV-DNA was reported in 80 subjects and anal HPV infection in 52 subjects. Anti-HPV IgG antibodies have been detected in 288 subjects. The overall prevalence of HPV exposition, considering actual and/or previous infection was 77.99%. Among infected men, high-risk HPV genotypes were detected in 66.08%. A total of 514 subjects were considered as the RF population, while 150 were classified in the non-RF population. There was a significantly higher prevalence of condylomatosis (odds ratio [OR] 4.07) and of seminal infection (OR 6.22) in the RF group.

Discussion and conclusion: These data represent an alert for the healthcare system to perform informative and screening campaigns for HPV infection in males and to promote HPV vaccination both in young people and for adult males with RF for HPV infections.

背景:人类乳头瘤病毒(HPV)是世界上最流行的性传播疾病。目的:了解未入选男性人群HPV感染现状及临床表现。材料和方法:共有718名男性参与了一项监测计划,在我单位完成了一次研究访问,包括精液采集、生殖道沟拭子擦拭和血液采集总抗hpv免疫球蛋白G (IgG)。当检测到HPV- dna时,我们进行了HPV荧光原位杂交,口腔和肛门拭子和阴茎镜检查。由于先前的研究表明,有HPV诱发病变史的受试者、有被诊断为HPV感染的伴侣或报告夫妻不育或性乱交的受试者、男性与男性发生性行为的受试者、无保护性交的受试者或重度吸烟者感染HPV的风险非常高,因此根据这些已知风险因素(RFs)的存在对患者进行分层。结果:718例患者中有401例(55.85%)检出HPV感染。口腔HPV- dna感染80例,肛门HPV感染52例。在288名受试者中检测到抗hpv IgG抗体。考虑到实际感染和/或既往感染,HPV暴露的总体患病率为77.99%。在感染男性中,检测到高危型HPV的比例为66.08%。共有514名受试者被认为是射频人群,而150名受试者被归类为非射频人群。RF组尖锐湿疣病(比值比[OR] 4.07)和精液感染(比值比[OR] 6.22)的患病率显著高于对照组。讨论和结论:这些数据提醒卫生保健系统开展男性HPV感染的信息和筛查活动,并促进年轻人和RF成年男性HPV感染的HPV疫苗接种。
{"title":"Prevalence of HPV infection in the general population of young and adult males in Italy.","authors":"Giuseppe Grande, Andrea Graziani, Luca De Toni, Federica Finocchi, Adriano Presciutti, Sara Corrò, Alberto Ferlin, Andrea Garolla","doi":"10.1111/andr.13817","DOIUrl":"https://doi.org/10.1111/andr.13817","url":null,"abstract":"<p><strong>Background: </strong>The most prevalent sexually transmitted disease in the world has the human papillomavirus (HPV) as its etiological agent.</p><p><strong>Objectives: </strong>To evaluate the prevalence of previous and actual HPV infection and the clinical manifestations in unselected males.</p><p><strong>Materials and methods: </strong>A total of 718 males participating to a surveillance program were asked to complete a study visit at our unit, including semen collection, balanopreputial sulcus swab, and blood collection for total anti-HPV immunoglobulin G (IgG). When HPV-DNA was detected, we performed HPV fluorescence in situ hybridization, oral and anal swab, and penoscopy. Because previous studies demonstrated a very high risk for HPV infection in subjects with history of HPV-induced lesions, with a partner with diagnosed HPV infection or reporting couple infertility or sexual promiscuity and an increase of the risk in males having sex with males, in subjects with unprotected sexual intercourses or in heavy smokers, patients were therefore stratified according to the presence of these known risk factors (RFs).</p><p><strong>Results: </strong>Actual HPV infection was detected in 401/718 subjects (55.85%). Oral HPV-DNA was reported in 80 subjects and anal HPV infection in 52 subjects. Anti-HPV IgG antibodies have been detected in 288 subjects. The overall prevalence of HPV exposition, considering actual and/or previous infection was 77.99%. Among infected men, high-risk HPV genotypes were detected in 66.08%. A total of 514 subjects were considered as the RF population, while 150 were classified in the non-RF population. There was a significantly higher prevalence of condylomatosis (odds ratio [OR] 4.07) and of seminal infection (OR 6.22) in the RF group.</p><p><strong>Discussion and conclusion: </strong>These data represent an alert for the healthcare system to perform informative and screening campaigns for HPV infection in males and to promote HPV vaccination both in young people and for adult males with RF for HPV infections.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765579","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
Prostate cancer and genetic contributions. 前列腺癌与基因的关系。
IF 3.2 2区 医学 Q1 ANDROLOGY Pub Date : 2024-11-29 DOI: 10.1111/andr.13812
Wesley H Chou, Cameron Chalker, Alexandra O Sokolova, Sudhir Isharwal

Prostate cancer remains a lethal disease for many men. Knowledge of genetic contributions to this condition has increasingly been used in its management. In this narrative review, we summarize various genetic alterations and syndromes associated with prostate cancer, including hereditary breast and ovarian cancer syndrome, Lynch syndrome, and hereditary prostate cancer, among others. Indications for germline testing are reviewed, as well as incorporation of genetic data at different phases of management for prostate cancer, such as screening and monitoring, and treatment of localized and metastatic disease.

前列腺癌仍然是许多男性的致命疾病。遗传因素对该病的影响已越来越多地用于该病的管理。在这篇叙述性综述中,我们总结了与前列腺癌相关的各种遗传改变和综合征,包括遗传性乳腺癌和卵巢癌综合征,Lynch综合征和遗传性前列腺癌等。本文回顾了生殖系检测的适应症,并在前列腺癌管理的不同阶段纳入遗传数据,如筛查和监测,以及局部和转移性疾病的治疗。
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引用次数: 0
Semen cryopreservation and storage in liquid nitrogen: Impact on chromatin compaction. 精液低温保存和液氮储存:对染色质压实的影响。
IF 3.2 2区 医学 Q1 ANDROLOGY Pub Date : 2024-11-29 DOI: 10.1111/andr.13806
Lara Tamburrino, Giulia Traini, Maria Emanuela Ragosta, Sara Dabizzi, Sara Vezzani, Flavia Scarpa, Linda Vignozzi, Elisabetta Baldi, Sara Marchiani

Background: Sperm cryopreservation is a consolidate option for long-term male fertility preservation. The freezing/thawing procedure causes detrimental effects to spermatozoa, including damage to viability, motility, membrane composition, and DNA, whereas the effect on sperm chromatin compaction is less studied.

Objectives: The primary aim of this study was to investigate the impact of cryopreservation on sperm chromatin compaction. Furthermore, the effect of cryopreservation on sperm parameters (motility, viability, chromatin compaction, and DNA fragmentation) was also assessed in relation to the storage time in liquid nitrogen.

Materials and methods: Semen samples, collected from 126 (92 normozoospermic and 34 oligozoospermic) patients undergoing routine semen analysis in the Andrology Laboratory of Careggi University Hospital of Florence, were frozen by conventional fast vapor freezing method. Sperm motility, viability, kinematic parameters (by computer-aided sperm analysis [CASA]), chromatin compaction (by staining with both aniline blue [AB] and Chromomycin A3 [CMA3]), and sperm DNA fragmentation (sDF, by TUNEL/Propidium Iodide [PI]) were evaluated before freezing and after thawing at different timepoints.

Results: After 7 days of storage, a significant decline in sperm motility, viability, and kinematics parameters, as well as a significant increase in the percentage of sperm positivity to CMA3, AB, and sDF, were observed. It is noteworthy that while motility and viability decreased in almost all subjects, the increase in CMA3 and AB positivity was observed in 68.0% and 79.2% of samples, respectively. A progressive deterioration of sperm motility and viability, less evident for chromatin structure, was observed at longer times of storage (28 and 180 days).

Discussion: Our results indicate that freezing/thawing procedures can alter chromatin structure. A reduction in protamine content and/or a modification in chromatin assembly can be hypothesized. Furthermore, the length of storage in liquid nitrogen appears to progressively affect sperm parameters, although it should be confirmed in larger cohort of subjects.

Conclusion: Current sperm cryopreservation protocols need to be improved with new strategies and personalized procedures aimed to minimize the damage.

背景:精子冷冻保存是长期保存男性生育能力的巩固选择。冷冻/解冻过程会对精子造成有害影响,包括对活力、活力、膜组成和DNA的损害,而对精子染色质压实的影响研究较少。目的:本研究的主要目的是探讨冷冻保存对精子染色质压缩的影响。此外,还评估了冷冻保存对精子参数(活力、活力、染色质压实和DNA片段化)的影响与液氮储存时间的关系。材料与方法:选取佛罗伦萨Careggi大学医院男科实验室常规精液分析患者126例(正常精子92例,少精子34例),采用常规快速蒸汽冷冻法进行冷冻。在冷冻前和解冻后的不同时间点评估精子活力、活力、运动学参数(通过计算机辅助精子分析[CASA])、染色质压实(通过苯胺蓝[AB]和色霉素A3 [CMA3]染色)和精子DNA碎片化(sDF,通过TUNEL/碘化丙烯[PI])。结果:保存7天后,精子活力、活力和运动学参数显著下降,精子CMA3、AB和sDF阳性百分比显著增加。值得注意的是,虽然几乎所有受试者的运动性和活力都有所下降,但CMA3和AB阳性分别在68.0%和79.2%的样本中有所增加。在较长的储存时间(28天和180天)中,精子活力和活力逐渐下降,而染色质结构则不太明显。讨论:我们的研究结果表明,冷冻/解冻过程可以改变染色质结构。可以假设是鱼精蛋白含量的减少和/或染色质组装的修饰。此外,在液氮中储存的时间似乎逐渐影响精子参数,尽管这需要在更大的受试者队列中得到证实。结论:目前的精子冷冻保存方案需要改进新的策略和个性化的程序,以尽量减少损害。
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引用次数: 0
A WHO 2021-based comprehensive scheme outlining sperm parameters' associations with IVF outcomes in PGT-A cycles. 基于世卫组织2021年的综合方案概述了PGT-A周期中精子参数与体外受精结果的关系。
IF 3.2 2区 医学 Q1 ANDROLOGY Pub Date : 2024-11-28 DOI: 10.1111/andr.13811
Rossella Mazzilli, Danilo Cimadomo, Federica Innocenti, Marilena Taggi, Greta Chiara Cermisoni, Sara Ginesi, Lisa Dovere, Laura Albricci, Maurizio Guido, Maria Rosaria Campitiello, Susanna Ferrero, Antonio Capalbo, Alberto Vaiarelli, Filippo Maria Ubaldi, Alberto Ferlin, Laura Rienzi, Gianluca Gennarelli

Objective: To examine the association between semen parameters, assessed according to World Health Organization (WHO)-2021 criteria, and paternal body mass index (BMI) and age, with embryological and clinical outcomes in ICSI cycles involving preimplantation genetic testing for aneuploidy (PGT-A).

Design: Retrospective study at a private in vitro fertilization (IVF) clinic.

Subjects: 3101 couples undergoing 4013 intracytoplasmic sperm injection (ICSI) + PGT-A cycles with own-oocytes (years 2013-2021).

Intervention: We performed trophectoderm biopsy, and comprehensive chromosome testing to report uniform aneuploidies and vitrified-warmed euploid single-blastocyst-transfers. Regression analyses adjusted for relevant confounders were conducted to outline putative associations of semen analysis and characteristics and paternal BMI and age with all embryological/clinical outcomes.

Results: Maternal age was the only significant confounding variable affecting euploidy blastocyst rate (EBR) (primary embryological outcome). When categorized, motility < 5th-percentile (-2.5%, 95%CI -4.9 to -0.2%, p = 0.03), concentration plus morphology < 5th-percentile (-2.7%,95%CI -4.8 to -0.6%, p = 0.01), concentration plus morphology plus motility < 5th-percentile (-4.0%,95%CI -5.5 to -2.6%, p < 0.01), obstructive-azoospermia [OA] (-5.5%,95%CI -9 to -2%, p = 0.02) and non-obstructive azoospermia (NOA) (-5.8%,95%CI -10.9 to -0.6%, p = 0.03) showed significantly lower results compared to all parameters > 5th-percentile. Furthermore, after adjusting for maternal age and the number of metaphase-II-oocytes inseminated, the only significant confounding variable affecting the chance of obtaining ≥ 1 live birth among completed cycles (primary clinical outcome) was basal and post sperm processing motility. When categorized, concentration plus morphology plus motility < 5th-percentile (multivariable-OR: 0.73, 95%CI 0.58-0.93, p = 0.01) and OA (multivariable-OR: 0.47, 95%CI 0.24-0.92, p = 0.03) showed significantly lower chances compared to all parameters > 5th-percentile. Advanced paternal age (defined as > 44 years) was associated only with lower day 5-blastocyst and Gardner's AA-grade (i.e., top quality) blastocyst rates.

Conclusions: This comprehensive analysis provides IVF professionals with useful figures to counsel infertile couples about their chances of success, taking into account the impact of semen characteristics and paternal BMI and age. These estimates are valuable for personalized decision-making about the most effective reproductive strategies to adopt, especially not underestimating male factor, by improving sperm concentration and motility whenever possible before assisted reproductive technologies.

目的:研究根据世界卫生组织(WHO)-2021标准评估的精液参数与父亲体重指数(BMI)和年龄之间的关系,以及包括植入前非整倍体基因检测(PGT-A)的ICSI周期的胚胎学和临床结果。设计:回顾性研究在一个私人体外受精(IVF)诊所。研究对象:3101对夫妇(2013-2021年)接受4013次卵母细胞胞浆内单精子注射(ICSI) + PGT-A周期。干预:我们进行了滋养外胚层活检和全面的染色体检测,以报告均匀的非整倍体和玻璃化加热的整倍体单囊胚移植。进行了校正相关混杂因素的回归分析,以概述精液分析和特征、父亲BMI和年龄与所有胚胎学/临床结果的推定关联。结果:母亲年龄是影响整倍体囊胚率(EBR)(主要胚胎学结局)的唯一显著混杂变量。分类时,运动性th-百分位数(-2.5%,95%CI -4.9至-0.2%,p = 0.03),浓度加形态学th-百分位数(-2.7%,95%CI -4.8至-0.6%,p = 0.01),浓度加形态学加运动性th-百分位数(-4.0%,95%CI -5.5至-2.6%,p = 5百分位数)。此外,在调整了母亲年龄和受精中期ii期卵母细胞的数量后,影响完整周期中获得≥1个活产机会(主要临床结局)的唯一显著混淆变量是精子加工后的基础活力和精子加工后活力。在分类时,浓度+形态学+运动度第th百分位(多变量or: 0.73, 95%CI 0.58 ~ 0.93, p = 0.01)和OA(多变量or: 0.47, 95%CI 0.24 ~ 0.92, p = 0.03)与所有参数第50百分位相比,概率显著降低。父亲年龄大(定义为55 - 44岁)仅与较低的第5天囊胚率和Gardner aa级(即高质量)囊胚率相关。结论:考虑到精液特征、父亲BMI和年龄的影响,这项综合分析为试管婴儿专业人员提供了有用的数据,为不孕夫妇提供了成功的机会。这些估计对于采取最有效的生殖策略的个性化决策是有价值的,特别是不要低估男性因素,通过在辅助生殖技术之前尽可能提高精子浓度和活力。
{"title":"A WHO 2021-based comprehensive scheme outlining sperm parameters' associations with IVF outcomes in PGT-A cycles.","authors":"Rossella Mazzilli, Danilo Cimadomo, Federica Innocenti, Marilena Taggi, Greta Chiara Cermisoni, Sara Ginesi, Lisa Dovere, Laura Albricci, Maurizio Guido, Maria Rosaria Campitiello, Susanna Ferrero, Antonio Capalbo, Alberto Vaiarelli, Filippo Maria Ubaldi, Alberto Ferlin, Laura Rienzi, Gianluca Gennarelli","doi":"10.1111/andr.13811","DOIUrl":"https://doi.org/10.1111/andr.13811","url":null,"abstract":"<p><strong>Objective: </strong>To examine the association between semen parameters, assessed according to World Health Organization (WHO)-2021 criteria, and paternal body mass index (BMI) and age, with embryological and clinical outcomes in ICSI cycles involving preimplantation genetic testing for aneuploidy (PGT-A).</p><p><strong>Design: </strong>Retrospective study at a private in vitro fertilization (IVF) clinic.</p><p><strong>Subjects: </strong>3101 couples undergoing 4013 intracytoplasmic sperm injection (ICSI) + PGT-A cycles with own-oocytes (years 2013-2021).</p><p><strong>Intervention: </strong>We performed trophectoderm biopsy, and comprehensive chromosome testing to report uniform aneuploidies and vitrified-warmed euploid single-blastocyst-transfers. Regression analyses adjusted for relevant confounders were conducted to outline putative associations of semen analysis and characteristics and paternal BMI and age with all embryological/clinical outcomes.</p><p><strong>Results: </strong>Maternal age was the only significant confounding variable affecting euploidy blastocyst rate (EBR) (primary embryological outcome). When categorized, motility < 5<sup>th</sup>-percentile (-2.5%, 95%CI -4.9 to -0.2%, p = 0.03), concentration plus morphology < 5<sup>th</sup>-percentile (-2.7%,95%CI -4.8 to -0.6%, p = 0.01), concentration plus morphology plus motility < 5<sup>th</sup>-percentile (-4.0%,95%CI -5.5 to -2.6%, p < 0.01), obstructive-azoospermia [OA] (-5.5%,95%CI -9 to -2%, p = 0.02) and non-obstructive azoospermia (NOA) (-5.8%,95%CI -10.9 to -0.6%, p = 0.03) showed significantly lower results compared to all parameters > 5<sup>th</sup>-percentile. Furthermore, after adjusting for maternal age and the number of metaphase-II-oocytes inseminated, the only significant confounding variable affecting the chance of obtaining ≥ 1 live birth among completed cycles (primary clinical outcome) was basal and post sperm processing motility. When categorized, concentration plus morphology plus motility < 5<sup>th</sup>-percentile (multivariable-OR: 0.73, 95%CI 0.58-0.93, p = 0.01) and OA (multivariable-OR: 0.47, 95%CI 0.24-0.92, p = 0.03) showed significantly lower chances compared to all parameters > 5<sup>th</sup>-percentile. Advanced paternal age (defined as > 44 years) was associated only with lower day 5-blastocyst and Gardner's AA-grade (i.e., top quality) blastocyst rates.</p><p><strong>Conclusions: </strong>This comprehensive analysis provides IVF professionals with useful figures to counsel infertile couples about their chances of success, taking into account the impact of semen characteristics and paternal BMI and age. These estimates are valuable for personalized decision-making about the most effective reproductive strategies to adopt, especially not underestimating male factor, by improving sperm concentration and motility whenever possible before assisted reproductive technologies.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749571","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
Therapeutic potential of hesperidin in diabetes mellitus-induced erectile dysfunction through Nrf2-mediated ferroptosis and oxidative stress. 橙皮甙通过 Nrf2 介导的铁氧化作用和氧化应激对糖尿病诱发的勃起功能障碍的治疗潜力
IF 3.2 2区 医学 Q1 ANDROLOGY Pub Date : 2024-11-25 DOI: 10.1111/andr.13814
Sheng Xin, Wen Song, Jiaquan Mao, Peng Hu, Zhong Chen, Jihong Liu, Xiaodong Song, Qian Fang, Kai Cui

Background: Among erectile dysfunction (ED) caused by metabolic abnormalities, diabetes mellitus-induced ED (DMED) progresses rapidly, manifests with severe symptoms, and shows reduced responsiveness to conventional medications. Hyperglycemia in the corpus cavernosum has been linked to the induction of both ferroptosis and oxidative stress, which are mediated by nuclear factor E2 related factor 2 (Nrf2). Hesperidin (Hes), a flavonoid compound, has been revealed to activate Nrf2 in certain diabetic complications, yet the efficacy of Hes on DMED and the specific mechanism remain unclear.

Objectives: To elucidate the potential mechanism and efficacy of Hes in regulating Nrf2-mediated ferroptosis and oxidative stress in DMED.

Materials and methods: DMED rats were constructed through the intraperitoneal injection of streptozotocin (STZ), partially supplemented with Hes. In parallel, in vitro research utilized human umbilical vein endothelial cells (HUVECs), with glucose addition to simulating a high glucose (HG) environment, and induced with Hes or ML385 (an Nrf2 inhibitor). Penile tissues and HUVECs were harvested for subsequent analyses.

Results: The results of this study indicate that Hes partially reversed the impaired erectile function. The expression of Nrf2, glutathione peroxidase 4 (GPX4), and heme oxygenase-1 (HO-1) in the corpus cavernosum elevated after supplementing with Hes, resulted in an inhibition in ferroptosis and oxidative stress. Moreover, the quantity and function of erectile effector cells were restored, and cavernous fibrosis was ameliorated. In HG-induced HUVECs, Hes ameliorated Nrf2-mediated ferroptosis and oxidative stress, effects which ML385 partially reversed.

Conclusions: Hes exerts a therapeutic effect on DMED rats and a regulatory mechanism on the Nrf2-HO-1/GPX4 axis, concurrently revitalizing endothelial and smooth muscle cells, and diminishing fibrosis. Our study provides robust preclinical evidence for employing Hes in treating DMED.

背景:在代谢异常引起的勃起功能障碍(ED)中,糖尿病诱发的ED(DMED)进展迅速,症状严重,对常规药物的反应性降低。海绵体内的高血糖与诱导铁变态反应和氧化应激有关,而这两种反应都是由核因子 E2 相关因子 2(Nrf2)介导的。研究发现,黄酮类化合物橙皮甙(Hes)在某些糖尿病并发症中可激活 Nrf2,但橙皮甙对 DMED 的疗效和具体机制仍不清楚:阐明Hes在DMED中调节Nrf2介导的铁蛋白沉积和氧化应激的潜在机制和疗效:通过腹腔注射链脲佐菌素(STZ)构建DMED大鼠,部分补充Hes。同时,体外研究利用人体脐静脉内皮细胞(HUVECs),添加葡萄糖模拟高糖(HG)环境,并用 Hes 或 ML385(一种 Nrf2 抑制剂)诱导。收获阴茎组织和 HUVECs 进行后续分析:研究结果表明,Hes 可部分逆转受损的勃起功能。补充 Hes 后,阴茎海绵体中 Nrf2、谷胱甘肽过氧化物酶 4(GPX4)和血红素加氧酶-1(HO-1)的表达升高,从而抑制了铁变态反应和氧化应激。此外,勃起效应细胞的数量和功能得到恢复,海绵体纤维化也得到改善。在 HG 诱导的 HUVECs 中,Hes 可改善 Nrf2 介导的铁变态反应和氧化应激,而 ML385 可部分逆转这些效应:Hes对DMED大鼠有治疗作用,并对Nrf2-HO-1/GPX4轴有调节机制,同时可活化内皮细胞和平滑肌细胞,减轻纤维化。我们的研究为使用 Hes 治疗 DMED 提供了可靠的临床前证据。
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引用次数: 0
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Andrology
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