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Neurotrophic effect of bone marrow mesenchymal stem cells for erectile dysfunction in diabetic rats 骨髓间充质干细胞对糖尿病大鼠勃起功能障碍的神经营养作用
Pub Date : 2012-03-19 DOI: 10.1111/j.1365-2605.2012.01250.x
C. Sun, H. Lin, W. Yu, X. Li, Y. Chen, X. Qiu, R. Wang, Y. Dai

It has been demonstrated that intracavernous injection of bone marrow-derived mesenchymal stem cells (BM-MSCs) had beneficial effects on improving erectile function in type-1 diabetic rats. This study was designed to investigate the neurotrophic effect of BM-MSCs for type-1 diabetic rats. Streptozocin-induced type-1 diabetic rats were randomly divided into three groups: diabetic group, BM-MSCs-treated group and BM-MSCs-conditioned medium-treated group. At the 3d, 1 and 2w time points after BM-MSCs injection, three randomly selected rats in MSCs group were sacrificed and penile samples were harvested to detect BM-MSCs in penile tissue. Four weeks after intracavernous injection of BM-MSCs or BM-MSCs-conditioned medium, intracavernous pressure (ICP) was assessed to evaluate the erectile function. Immunohistochemistry was used to track labelled BM-MSCs in penile tissue and to detect neuronal nitric oxide synthase (nNOS) and neurofilament (NF) positive fibres in penile dorsal nerve. Enzyme lined immunosorbent assay (ELISA) was used to measure the concentrations of vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in BM-MSCs-conditioned medium. BM- MSCs secreted detectable levels of VEGF, BDNF and NGF. Intracavernous injection of BM-MSCs improved erectile function in diabetic rats. The functional improvement was accompanied by promoted nNOS and NF positive nerve fibres within penile dorsal nerve in type-1 diabetic rats. Histological data revealed a time-dependent decrease in the number of BM-MSCs in the corpus cavernosum following injection. Furthermore, the beneficial effect of BM-MSCs was partially repeated by BM-MSCs-conditioned medium. Intracavernous injection of BM-MSCs is effective in improving nerve regeneration in diabetic rats. Paracrine effects of BM-MSCs are probably involved in the improvement.

海绵体内注射骨髓间充质干细胞(BM-MSCs)对改善1型糖尿病大鼠勃起功能有有益作用。本研究旨在探讨脑基质间充质干细胞对1型糖尿病大鼠的神经营养作用。将链脲佐菌素诱导的1型糖尿病大鼠随机分为3组:糖尿病组、脑基质间充质干细胞处理组和脑基质间充质干细胞条件中等处理组。在注射骨髓间充质干细胞后3d、1、2w时间点,随机选取MSCs组大鼠3只,处死,取阴茎标本,检测阴茎组织中的骨髓间充质干细胞。在海绵内注射脑髓间充质干细胞或脑髓间充质干细胞培养基4周后,评估海绵内压力(ICP)以评估勃起功能。采用免疫组化方法对阴茎组织中标记的BM-MSCs进行跟踪,检测阴茎背神经中神经元型一氧化氮合酶(nNOS)和神经丝(NF)阳性纤维。采用酶联免疫吸附法(ELISA)测定脑-间充质干细胞条件培养基中血管内皮生长因子(VEGF)、神经生长因子(NGF)和脑源性神经营养因子(BDNF)的浓度。骨髓间充质干细胞分泌可检测水平的VEGF、BDNF和NGF。海绵内注射脑基质干细胞可改善糖尿病大鼠勃起功能。1型糖尿病大鼠阴茎背神经内nNOS和NF阳性神经纤维增加,功能改善。组织学数据显示,注射后海绵体中BM-MSCs的数量呈时间依赖性减少。此外,BM-MSCs的有益作用在BM-MSCs条件培养基中部分重复。海绵体内注射脑基质间充质干细胞对糖尿病大鼠神经再生有促进作用。骨髓间充质干细胞的旁分泌作用可能参与了这种改善。
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引用次数: 63
Effects of inducible nitric oxide synthase (iNOS) deficiency in mice on Sertoli cell proliferation and perinatal testis development 诱导型一氧化氮合酶(iNOS)缺乏对小鼠支持细胞增殖和围产期睾丸发育的影响
Pub Date : 2012-03-15 DOI: 10.1111/j.1365-2605.2012.01264.x
S. A. Auharek, N. L. M. Lara, G. F. Avelar, R. M. Sharpe, L. R. França

Nitric oxide (NO) plays crucial roles in several physiological and pathological conditions. The iNOS isoform produces high levels of NO independent of intracellular calcium and, in the testis, which is expressed in Sertoli (SC), Leydig (LC) and germ cells. The testicular roles of NO are unclear, but it can inhibit LC testosterone production. Our aim was to evaluate the effects of iNOS deficiency on testis development in mice from late fetal life through early puberty. Therefore, testes from wild type (C57BCL/6) and iNOS−/− mice (B6.129P2- Nos2tm1Lau/J) were sampled at various ages between e18.5 and Pnd20 and evaluated by histological and stereological analyses; proliferating cells were labelled with 3H-thymidine. At all ages, testis weight and anogenital index, a measure of fetal androgen exposure, were greater in iNOS-deficient mice than in wild type mice. At all ages after birth, iNOS-deficient mice exhibited increased (p < 0.05) SC number per testis, and this was accounted for by a higher SC proliferation index (p < 0.05) in iNOS-deficient mice, especially on Pnd1 and Pnd5. Similarly, LC number per testis was higher (p < 0.05) in iNOS−/− mice than in wild type at all post-natal ages. Highly positive and significant correlations were observed between the proliferation index for SC, LC and peritubular myoid cells on e18.5 and post-natally. Although lumen formation was slightly advanced in iNOS−/− mice, no obvious other effects on pubertal testis development were observed. These results imply that NO may normally constrain testis somatic cell development, especially SC, perhaps by limiting testosterone production. Removal of this constraint results in normal, but larger, testes with greater sperm production. Our data pinpoint the window of iNOS (NO) action on SC proliferation and raise the possibility that experimental manipulation of NO in early post-natal life could be used to enhance SC proliferation if this was deficient for any reason.

一氧化氮(NO)在许多生理和病理条件中起着至关重要的作用。iNOS异构体产生高水平的NO,不依赖于细胞内钙,在睾丸中,在支持细胞(SC)、间质细胞(LC)和生殖细胞中表达。NO在睾丸中的作用尚不清楚,但它可以抑制LC睾酮的产生。我们的目的是评估iNOS缺乏对小鼠从胎儿晚期到青春期早期睾丸发育的影响。因此,从野生型(C57BCL/6)和iNOS - / -小鼠(B6.129P2- Nos2tm1Lau/J)的e18.5和Pnd20之间的不同年龄取样睾丸,并进行组织学和体力学分析;增殖细胞用3h -胸腺嘧啶标记。在所有年龄段,inos缺陷小鼠的睾丸重量和肛门生殖指数(胎儿雄激素暴露的一种衡量指标)都高于野生型小鼠。在出生后的所有年龄段,inos缺陷小鼠的每睾丸SC数均增加(p < 0.05),这是由于inos缺陷小鼠的SC增殖指数较高(p < 0.05),尤其是Pnd1和Pnd5。同样,iNOS - / -小鼠的每个睾丸LC数在所有出生后年龄均高于野生型(p < 0.05)。SC、LC和小管周围肌样细胞的增殖指数在18 ~ 5岁及出生后呈极显著正相关。虽然iNOS - / -小鼠的管腔形成稍微提前,但对青春期睾丸发育没有明显的其他影响。这些结果表明,NO可能通过限制睾丸激素的产生来限制睾丸体细胞的发育,尤其是SC。消除这种限制会导致正常但更大的睾丸和更多的精子生产。我们的数据确定了iNOS (NO)对SC增殖作用的窗口,并提出了在出生后早期生命中实验操作NO可用于增强SC增殖的可能性,如果这种能力因任何原因不足的话。
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引用次数: 28
Relationship between conventional sperm parameters and motile sperm organelle morphology examination (MSOME) 精子常规参数与活动精子细胞器形态学检查的关系
Pub Date : 2012-03-15 DOI: 10.1111/j.1365-2605.2012.01249.x
A. Perdrix, R. Saïdi, J. F. Ménard, E. Gruel, J. P. Milazzo, B. Macé, N. Rives

With the motile sperm organelle morphology examination (MSOME), spermatozoa morphology may be assessed directly on motile spermatozoa at high magnification (up to 6600×). This procedure describes more precisely spermatozoa abnormalities, especially head vacuoles. However, no consensus has been established concerning normal or abnormal MSOME criteria. The aim of our study was to define MSOME vacuole criteria assessed objectively with a digital imaging system software to establish a potential relationship between conventional semen parameters. A total of 440 semen samples were obtained from males consulting in Rouen University Hospital Reproductive Biology Laboratory. Conventional semen analysis (volume, sperm concentration, progressive motility, vitality and morphology) and MSOME assessment {sperm head length, width and area as well as vacuole number, vacuole area and relative vacuole area to sperm head [RVA (%) = [vacuole area (μm2)/head area (μm2)] × 100)]} were performed for each semen sample. Among our 440 males, 109 presented normal conventional semen parameters and 331 abnormal ones. Sperm head vacuoles were significantly larger in abnormal semen samples (p < 0.0001). RVA was the most discriminative MSOME criterion between normal and abnormal semen samples according to ROC curves analysis, and was negatively correlated with poor sperm morphology (r = −0.53, p < 0.0001). We concluded to (i) the normal occurrence of vacuoles in sperm head whatever the normality or abnormality of semen parameters, (ii) the discriminative function of the RVA to distinguish semen samples with normal and abnormal parameters, and (iii) the strong correlation between high RVA and poor sperm morphology.

通过运动精子细胞器形态学检查(MSOME),可以在高倍率(高达6600倍)下直接在运动精子上评估精子形态。这种方法更准确地描述了精子异常,特别是头部空泡。然而,关于正常或异常的MSOME标准尚未达成共识。我们的研究目的是定义MSOME液泡标准,用数字成像系统软件客观评估,以建立常规精液参数之间的潜在关系。在鲁昂大学医院生殖生物学实验室咨询的男性共获得440份精液样本。对每个精液样本进行常规精液分析(体积、精子浓度、进动、活力和形态)和MSOME评估{精子头长、宽度和面积以及液泡数、液泡面积和相对于精子头的液泡面积[RVA(%) =[液泡面积(μm2)/头面积(μm2)] × 100]}。440例男性精液常规参数正常109例,异常331例。异常精液样本的精子头空泡明显较大(p < 0.0001)。ROC曲线分析显示,RVA是正常与异常精液样本最具判别性的MSOME标准,与精子形态不良呈负相关(r = - 0.53, p < 0.0001)。我们得出的结论是:(1)无论精液参数是否正常,精子头部都会出现液泡;(2)RVA在区分精液样本的正常和异常参数方面具有区分功能;(3)高RVA与差精子形态之间存在很强的相关性。
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引用次数: 56
Differences in the clinical characteristics between young and elderly men with varicocoele 青年和老年男性精索静脉曲张临床特征的差异
Pub Date : 2012-03-15 DOI: 10.1111/j.1365-2605.2012.01257.x
S.-S. Chen

Information concerning the clinical characteristics in elderly men with varicocoele is relatively limited. This study was assessed to evaluate the differences in clinical characteristics between young and elderly patients with varicocoele by retrospective chart review. Between June 2003 and February 2011, 169 young (18–30 years) men and 156 elderly (45–55 years) men with varicocoele, and 30 age-matched men without varicocoele were recruited for this study. All the patients were divided into six groups. Thirty-one infertile patients were assigned to Group 1, 138 fertile patients to Group 2, 35 infertile patients to Group 3 and 121 fertile patients to Group 4. Group 5 (15 young) and 6 (15 elderly) were control groups. The parameters for comparison included body mass index (BMI), semen quality (sperm motility, morphology and density) and pH value, serum concentration of follicle-stimulating hormone (FSH), luteinizing hormones (LH), testosterone, testicular volume, grade of varicocoele and peak retrograde flow (PRF) and maximal vein diameter (MVD) by colour Doppler ultrasound (CDS). Elderly men with varicocoele had a higher incidence of bilateral varicocoele (25.5% vs. 14.8%), but a lower incidence of unilateral right varicocoele (2.6% vs. 7.7%) than young patients with varicocoele. In addition, patients with varicocoele had lower BMI than those without, and infertile young patients with varicocoele had the lowest levels of BMI. Furthermore, infertile patients (Groups 1 and 3) with varicocoele had significantly lower testicular volume and semen pH, lower levels of testosterone, higher levels of FSH and LH and higher PRF than fertile men with varicocoele (Groups 2 and 4). In conclusion, infertile elderly patients with varicocoele had significantly lower levels of testosterone and higher levels of FSH and LH than infertile young men with varicocoele. In addition, infertile elderly patients with bilateral varicocoele (Group 3, n = 8) had the lowest levels of testosterone.

老年男性精索静脉曲张的临床特征资料相对有限。本研究通过回顾性的图表回顾来评估年轻和老年精索静脉曲张患者临床特征的差异。在2003年6月至2011年2月期间,169名患有精索静脉曲张的年轻男性(18-30岁)和156名患有精索静脉曲张的老年男性(45-55岁),以及30名没有精索静脉曲张的年龄匹配的男性被招募入本研究。所有患者分为6组。31例不孕症患者分为第1组,138例可育患者分为第2组,35例可育患者分为第3组,121例可育患者分为第4组。第5组(青少年15例)和第6组(老年人15例)为对照组。比较的参数包括身体质量指数(BMI)、精液质量(精子活力、形态和密度)和pH值、血清促卵泡激素(FSH)、促黄体生成素(LH)、睾酮、睾丸体积、精索静脉曲张程度、逆行血流峰值(PRF)和最大静脉直径(MVD)。老年男性精索静脉曲张的双侧发生率较高(25.5%比14.8%),但单侧右侧精索静脉曲张的发生率较低(2.6%比7.7%)。此外,有精索静脉曲张的患者BMI低于无精索静脉曲张的患者,而有精索静脉曲张的不孕青年患者BMI最低。此外,不育的精索静脉曲张患者(1组和3组)睾丸体积和精液pH值明显低于有生育能力的精索静脉曲张男性(2组和4组),睾酮水平较低,FSH和LH水平较高,PRF水平较高。综上所述,老年不育的精索静脉曲张患者睾酮水平明显低于有生育能力的青年精索静脉曲张男性,FSH和LH水平明显高于有生育能力的青年精索静脉曲张男性。此外,伴有双侧静脉曲张的老年不育患者(第3组,n = 8)睾酮水平最低。
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引用次数: 10
Retracted: Effects of exposure to a mobile phone on testicular function and structure in adult rabbit 撤下:接触手机对成年家兔睾丸功能和结构的影响
Pub Date : 2012-03-14 DOI: 10.1111/j.1365-2605.2012.01271.x
Nader Salama, Tomoteru Kishimoto, Hiro-omi Kanayama

The following article from the International Journal of Andrology 33: 88–94, 2010, ‘Effects of exposure to a mobile phone on testicular function and structure in adult rabbit’ by Nader Salama, Tomoteru Kishimoto and Hiro-omi Kanayama, published online on 9 December 2008 in Wiley Online Library (http://www.wileyonlinelibrary.com), has been withdrawn at the request of the author and agreed with the journal’s current and past Editors-in-Chief, Ewa Rajpert-De Meyts and Jorma Toppari, and Blackwell Publishing Ltd. The retraction has been agreed due to lack of approval of the article by co-authors, lack of evidence to justify the accuracy of the data presented in the article and overlap of data and figures between this article and two others, Systems Biology in Reproductive Medicine, 55:181–187, 2009 ‘The Mobile Phone Decreases Fructose but not Citrate in Rabbit Semen’ by Nader Salama, Tomoteru Kishimoto, Hiro-omi Kanayama, and Susumu Kagawa and International Journal of Impotence Research 22: 127–33, 2010, ‘Effects of exposure to a mobile phone on sexual behavior in adult male rabbit: an observational study’ by Salama N, Kishimoto T, Kanayama HO, Kagawa S.

Ewa Rajpert-De Meyts

Editor-in-Chief

International Journal of Andrology

以下文章摘自《国际男科杂志》第33期:2010年第88-94期,Nader Salama, Tomoteru Kishimoto和hiroomi Kanayama发表的“接触手机对成年兔子睾丸功能和结构的影响”,2008年12月9日在线发表在Wiley在线图书馆(http://www.wileyonlinelibrary.com),应作者的要求,该期刊现任和前任主编Ewa Rajpert-De Meyts和Jorma Toppari以及Blackwell出版有限公司已同意撤回。由于缺乏共同作者对文章的认可,缺乏证据来证明文章中数据的准确性,以及这篇文章与另外两篇文章之间的数据和数字重叠,《生殖医学系统生物学》,55:181-187,2009年,Nader Salama, Tomoteru Kishimoto, hiroomi Kanayama和Susumu Kagawa在《国际阳痿研究杂志》上发表的“手机减少了兔子精液中的果糖而不是柠檬酸盐”。2010年,“接触手机对成年雄性兔子性行为的影响:一项观察性研究”,作者:Salama N, Kishimoto T, Kanayama HO, Kagawa S.Ewa Rajpert-De meytsetor -in- the international Journal of Andrology
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引用次数: 5
‘ANDROLOGY’– The New Journal of the American Society of Andrology and the European Academy of Andrology “男科学”——美国男科学会和欧洲男科学会的新期刊
Pub Date : 2012-03-13 DOI: 10.1111/j.1365-2605.2012.01261.x
M. L. Meistrich, I. T. Huhtaniemi

Andrology is the study of health issues specific to men, with a focus on basic aspects of their reproductive system (gonads, endocrine and accessory organs), and diagnosis and treatment of medical problems associated with infertility, sexual dysfunction and urological problems. In medicine, the development of Andrology as a specific specialty is rather recent; it had often been considered a subspecialty of urology or endocrinology. The field of Andrology, emerging over the last 40 years, has produced several specialty journals covering both the basic scientific and clinical areas. The International Journal of Andrology (IJA) began publication in 1978 and became the official journal of the European Academy of Andrology (EAA) in 1992. The American Society of Andrology (ASA) launched the Journal of Andrology (JA) in 1980. These two Journals have been the leading journals in the field of Andrology with current impact factors of 3.6 (IJA) and 3.1 (JA).

Andrology remains a small and specialized field, and the size of both journals has been modest, each publishing about 600 pages per year. With the goal of increasing the visibility, impact and prominence of both journals, and to better promote the field of Andrology the EAA and ASA have decided jointly to create a single, even more prominent journal, Andrology. The international spirit of cooperation between the two societies and the enhanced availability of worldwide electronic communication has made it possible to jointly publish this new journal. The two societies will share equally in the management and editorial decisions of Andrology and in profits and losses from journal revenues and expenses.

The two original journals will actively continue to publish throughout 2012, with the last issues being published as November/December 2012 issues. New papers submitted to these journals will be accepted for review through the 31 March 2012. We encourage members of the two societies to continue to send their best work to JA or IJA so that we can keep the journals strong as we go into the merger. It is possible that some papers submitted to the original journals that need to be sent back to authors for significant revisions might not be accepted in time. If they are accepted later, they will appear in Andrology. Starting in late 2012, the back issues of both JA and IJA will be hosted on-line at the Wiley Online Library.

The EAA and ASA are pleased to announce that a contract has been signed with Wiley-Blackwell, publisher of the IJA, for publication of Andrology. The Journal will be published both in print and on-line, bimonthly, with accepted articles published on-line shortly after acceptance. We believe that there will be cost savings to both societies by eliminating duplications of effort in publishing and that the merged journal will result in increased profitability and income for the benefit of both societies. Ewa Rajpert-De Meyts M.D., Ph.D. of the Rig

男科是专门研究男性健康问题的学科,重点是男性生殖系统(性腺、内分泌和辅助器官)的基本方面,以及与不育症、性功能障碍和泌尿系统问题有关的医学问题的诊断和治疗。在医学上,男科作为一个特殊的专业是最近才发展起来的;它经常被认为是泌尿科或内分泌科的一个亚专科。男科领域,在过去的40年里兴起,已经产生了一些涵盖基础科学和临床领域的专业期刊。国际男科杂志(IJA)于1978年创刊,1992年成为欧洲男科学会(EAA)的官方期刊。美国男科学会(ASA)于1980年创办了《男科杂志》(JA)。这两本期刊目前的影响因子分别为3.6 (IJA)和3.1 (JA),在男科领域处于领先地位。男科仍然是一个小而专业的领域,两家期刊的规模都不大,每年出版约600页。为了提高两家期刊的知名度、影响力和知名度,并更好地促进男科学领域的发展,EAA和ASA决定共同创办一本更知名的期刊《男科学》。两个学会之间的国际合作精神和全球电子通信的增强使联合出版这本新杂志成为可能。这两个协会将平等分享《男科学》的管理和编辑决策,以及期刊收入和支出的盈亏。这两本原始期刊将在2012年积极地继续出版,最后一期将在2012年11月/ 12月出版。在2012年3月31日之前,这些期刊将接受新论文的评审。我们鼓励两个协会的成员继续向JA或IJA提交他们最好的作品,这样我们就可以在合并时保持期刊的强大。一些提交到原期刊的论文可能需要发回给作者进行重大修改,可能无法及时被接受。如果他们后来被接受,他们将出现在男科。从2012年底开始,《JA》和《IJA》的过期刊都将在Wiley在线图书馆上线。EAA和ASA高兴地宣布与IJA的出版商Wiley-Blackwell签订了一份关于出版《男科学》的合同。《期刊》将以印刷版和网络版两种形式出版,双月刊,接受的文章在接受后不久就在网上发表。我们相信,通过消除出版工作的重复,将为两个学会节省成本,合并后的期刊将增加两个学会的盈利能力和收入。哥本哈根大学Rigshospitalet的Ewa Rajpert-De Meyts医学博士和犹他大学医学院的Douglas Carrell博士被选为联合主编。ASA会员(包括学员)和监管局会员可在网上订阅《男科学》杂志,并可额外收取适量的印刷版订阅费用。新期刊的更大发行量将有利于作者;此外,协会成员现在可以访问原本在单独期刊上的内容。我们相信,这个更大的合并期刊可以更有效地与其他期刊竞争,并吸引更好的文章。这本更著名的杂志应该会提高男科学科的声望。《男科》将继续发表男科的基础、转化、临床和流行病学研究,并将包括两本原始期刊中强调的所有主题。这些领域包括荷尔蒙调节、精子发生、生殖道、附属性器官和外生殖器、精子功能和质量、前列腺疾病(包括癌症)和男性性生理。将考虑使用哺乳动物和非哺乳动物模型系统以及分子和细胞研究来了解人类和重要动物物种的男性生殖健康和功能。此外,临床男科和男科实验室科学指南以及ASA和EAA协会信息将出现在《男科》杂志上。期刊影响因子每年(每年6月)由科学信息研究所(ISI)在《汤森路透期刊引用报告》中公布。虽然男科学需要几年的时间才能完全建立自己的影响因子,但IJA、JA和男科学的综合影响因子可以计算得到一个影响因子,作者可以用它来记录他们发表的期刊的影响。 2014年6月ISI影响因子报告将分别列出IJA和JA,并表示2013年对2011年和2012年期刊文章的引用数除以这两年的文章发表数;分子和分母可以很容易地结合起来计算对两个原始期刊的总体影响。2015年ISI影响因子将列出IJA、JAndrol和Andrology。IJA和JAndrol的数字是2014年对2012年发表的文章的引用数除以2012年发表的文章数;对于男科学,影响因子是2014年对2013年发表的文章的引用数除以2013年发表的文章数。总体影响因子可以通过结合所有三个分子和分母来计算。因此,在转换过程中可以获得原始和合并期刊的有效影响因子。从2016年起,ISI数据库中只会出现新期刊《Andrology》的影响因子。基于我们对合并期刊的目标,ASA和EAA对合并的大力支持,以及优秀的编辑和出版团队,我们预计最终的影响因子将超过JA和IJA。第一期《男科学》将于2013年1月出版。一个使用Scholar One手稿在线提交和同行评审系统的提交网站于2012年4月初开放,用于提交男科学原创研究的新手稿。编辑将征集可能优秀的评审文章,有评审建议的个人应联系总编辑之一。我们鼓励ASA和EAA成员通过提交他们最好的论文来支持《男科学》的发行,特别是在杂志最重要的头几年。
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引用次数: 4
Expression of the vitamin D metabolizing enzyme CYP24A1 at the annulus of human spermatozoa may serve as a novel marker of semen quality 人精子环上维生素D代谢酶CYP24A1的表达可能作为一种新的精液质量标志
Pub Date : 2012-03-09 DOI: 10.1111/j.1365-2605.2012.01256.x
M. Blomberg Jensen, A. Jørgensen, J. E. Nielsen, P. J. Bjerrum, M. Skalkam, J. H. Petersen, D. L. Egeberg, S. Bangsbøll, A. N. Andersen, N. E. Skakkebæk, A. Juul, E. Rajpert-De Meyts, S. Dissing, H. Leffers, N. Jørgensen

Vitamin D (VD) is important for male reproduction in mammals and the VD receptor (VDR) and VD-metabolizing enzymes are expressed in human spermatozoa. The VD-inactivating enzyme CYP24A1 titrates the cellular responsiveness to VD, is transcriptionally regulated by VD, and has a distinct expression at the sperm annulus. Here, we investigated if CYP24A1 expression serves as a marker for VD metabolism in spermatozoa, and whether CYP24A1 expression was associated with semen quality. We included 130 men (53 healthy young volunteers and 77 subfertile men) for semen analysis and immunocytochemical (ICC) detection of CYP24A1. Another 40 men (22 young, 18 subfertile) were tested for in vitro effects of 1,25(OH)2D3 on intracellular calcium concentration ([Ca2+]i) and sperm motility. Double ICC staining showed that CYP24A1 and VDR were either concomitantly expressed or absent in 80% of the spermatozoa from young men. The median number of CYP24A1-expressing spermatozoa was 1% in subfertile men and thus significantly (p < 0.0005) lower than 25% in spermatozoa from young men. Moreover, CYP24A1 expression correlated positively with total sperm count, -concentration, -motility and -morphology (all p < 0.004), and the percentage of CYP24A1-positive spermatozoa increased (15 vs. 41%, p < 0.0005) after percoll-gradient-centrifugation. We noticed that the presence of >3% CYP24A1-positive spermatozoa distinguished young men from subfertile men with a sensitivity of 66.0%, a specificity of 77.9% and a positive predictive value of 98.3%. Functional studies revealed that 1,25(OH)2D3 increased [Ca2+]i and sperm motility in young healthy men, while 1,25(OH)2D3 was unable to increase motility in subfertile patients. In conclusion, we suggest that CYP24A1 expression at the annulus may serve as a novel marker of semen quality and an objective proxy for sperm function.

维生素D (VD)在哺乳动物雄性生殖中起着重要作用,而VD受体(VDR)和VD代谢酶在人类精子中表达。VD灭活酶CYP24A1测定细胞对VD的反应性,受VD的转录调节,在精子环上有明显的表达。在这里,我们研究了CYP24A1的表达是否作为精子中VD代谢的标志,以及CYP24A1的表达是否与精液质量有关。我们纳入了130名男性(53名健康青年志愿者和77名不育男性)进行精液分析和免疫细胞化学(ICC)检测CYP24A1。另外40名男性(22名年轻男性,18名不育男性)接受了125 (OH)2D3对细胞内钙浓度([Ca2+]i)和精子活力的体外影响测试。双ICC染色显示CYP24A1和VDR在80%的年轻男性精子中同时表达或不存在。在低生育能力男性中,表达cyp24a1的精子中位数为1%,因此显著(p < 0.0005)低于年轻男性精子中的25%。此外,CYP24A1的表达与精子总数、-浓度、-活力和-形态呈正相关(p < 0.004),并且在过柱梯度离心后,CYP24A1阳性精子的比例增加(15比41%,p < 0.0005)。我们注意到,3% cyp24a1阳性精子的存在将年轻男性与低生育能力男性区分开来,敏感性为66.0%,特异性为77.9%,阳性预测值为98.3%。功能研究显示,1,25(OH)2D3增加了年轻健康男性的[Ca2+]i和精子活力,而1,25(OH)2D3不能增加不孕患者的活力。综上所述,我们认为环上CYP24A1的表达可能作为精液质量的新标记和精子功能的客观指标。
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引用次数: 82
Early breast development in girls after prenatal exposure to non-persistent pesticides 产前接触非持久性杀虫剂后女孩的早期乳房发育
Pub Date : 2012-03-09 DOI: 10.1111/j.1365-2605.2011.01244.x
C. Wohlfahrt-Veje, H. R. Andersen, I. M. Schmidt, L. Aksglaede, K. Sørensen, A. Juul, T. K. Jensen, P. Grandjean, N. E. Skakkebæk, K. M. Main
Contemporary American and European girls experience breast development at earlier ages compared with 15-20 years ago. Alterations in BMI alone cannot account for these changes. Several currently used pesticides possess endocrine disrupting properties and may interfere with reproductive development, but human data are sparse. We examined girls whose mothers worked in greenhouses in the first trimester of pregnancy to assess the long-term effects of prenatal pesticide exposure on puberty. Mothers were prenatally categorized as exposed or unexposed to pesticides. We studied the offspring of these greenhouse workers, and evaluated the anthropometry, pubertal staging in the girls, and blood samples were drawn at 3 months of age (n = 90) and again once at school age (6-11 years, n = 83). No clinical and biochemical differences were found between the exposed and unexposed girls at 3 months of age. Mean onset of B2+ was 8.9 years (95% CI: 8.2; 9.7) in prenatally exposed girls, compared with 10.4 years (9.2; 17.6) in the unexposed (p = 0.05), and 10.0 (9.7-10.3) years in a Danish reference population (p = 0.001). Exposed girls had higher serum androstenedione levels (geometric means: 0.58 vs. 0.79 nmol/L, p = 0.046) and lower Anti-Müllerian Hormone (AMH) compared with the unexposed (geometric means: 16.4 vs. 21.3 pmol/L, p > 0.05) and the reference group (20.2 pmol/L, p = 0.012). Levels of testosterone, estradiol, prolactin, FSH, LH, SHBG, DHEAS, DHT, Inhibin A and Inhibin B did not differ between the groups. In conclusion, our findings suggest that prenatal exposure to currently approved pesticides may cause earlier breast development in girls. This association appeared not to be because of changes in gonadotropins, but rather to higher androgen levels, which indirectly may increase oestrogens through aromatization. In addition, lower serum AMH levels indicated a reduced pool of antral ovarian follicles. The long-term consequences of our findings with regard to establishment of future reproductive function still remain unknown.
与15-20年前相比,当代美国和欧洲女孩乳房发育的年龄更早。单靠BMI的改变并不能解释这些变化。目前使用的几种农药具有内分泌干扰特性,可能干扰生殖发育,但人类数据很少。我们调查了母亲在怀孕前三个月在温室工作的女孩,以评估产前农药暴露对青春期的长期影响。母亲在产前被分为接触和未接触杀虫剂两类。我们研究了这些温室工人的后代,并评估了这些女孩的人体测量学、青春期发育阶段,并在3个月大时(n = 90)抽取了血液样本,在学龄期(6-11岁,n = 83)再次抽取了血液样本。在3个月大时,暴露组和未暴露组的女孩没有临床和生化差异。B2+的平均起病时间为8.9年(95% CI: 8.2;在产前暴露的女孩中为9.7岁,相比之下为10.4岁(9.2岁;未暴露人群为17.6岁(p = 0.05),丹麦参考人群为10.0(9.7-10.3)岁(p = 0.001)。与未暴露组(几何平均:16.4比21.3 pmol/L, p > 0.05)和对照组(20.2 pmol/L, p = 0.012)相比,暴露组女童血清雄烯二酮水平(几何平均:0.58比0.79 nmol/L, p = 0.046)较高,抗勒氏激素(AMH)较低。睾酮、雌二醇、催乳素、FSH、LH、SHBG、DHEAS、DHT、抑制素A和抑制素B的水平在两组之间没有差异。总之,我们的研究结果表明,产前暴露于目前批准的农药可能会导致女孩乳房发育提前。这种关联似乎不是由于促性腺激素的变化,而是由于更高的雄激素水平,这可能通过芳构化间接增加雌激素。此外,较低的血清AMH水平表明卵巢窦卵泡池减少。我们的发现对建立未来生殖功能的长期影响仍然未知。
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引用次数: 53
Serum from patients with erectile dysfunction inhibits circulating angiogenic cells from healthy men: relationship with cardiovascular risk, endothelial damage and circulating angiogenic modulators 勃起功能障碍患者血清抑制健康男性循环血管生成细胞:与心血管风险、内皮损伤和循环血管生成调节剂的关系
Pub Date : 2012-03-06 DOI: 10.1111/j.1365-2605.2012.01253.x
F. Pelliccione, A. D’Angeli, S. Filipponi, S. Falone, S. Necozione, A. Barbonetti, F. Francavilla, S. Francavilla

Erectile dysfunction (ED) is an early manifestation of arteriosclerosis associated with endothelial damage/dysfunction and to a blunted ability of cultured mononuclear circulating cells (MNCs) to differentiate circulating angiogenic cells (CACs), putatively involved in endothelial damage repair. Here we explored effects of human serum (HS) from patients with ED and cardiovascular risk factors (VRFs) but no clinical atherosclerosis, on cultured MNCs of healthy men to differentiate CACs and to form colonies. Effect of HS on number of CACS and of colony forming units (CFUs) was correlated with circulating markers of endothelial damage and with angiogenic modulators. MNCs from healthy men were cultured in standard conditions or with 20% HS from 35 patients with ED and from 10 healthy men. CACs were identified after 7 days of culture by uptake of acetylated low-density lipoprotein with concomitant binding of Ulex europaeus agglutinin I. CFUs were counted after 5 days of culture. Enzyme-linked immunosorbent assays assessed plasmatic soluble (s) form of E-selectin, Endothelin (ET)-1, tissue type plasminogen activator (tPA), vascular endothelial growth factor (VEGF)165 and sVEGF receptor (R)-1. The number of CACs and of CFUs from healthy men was reduced after culturing MNCs with HS compared to standard medium. The inhibitory effect was significantly higher with HS from ED patients with higher or lower VRF exposure compared to healthy men. Inhibition was positively correlated with VRFs exposure, with ED severity, with common carotid artery intima media thickness measured using B-mode ultrasound, and to a lesser extent with plasmatic sE-Selectin, sET-1 and sVEGFR-1. Dysfunction of cells involved in vascular homoeostasis is induced by soluble factors still unknown and already present in a very initial systemic vascular disease in men with ED and VRFs.

勃起功能障碍(ED)是动脉硬化的早期表现,与内皮损伤/功能障碍和培养的单核循环细胞(MNCs)分化循环血管生成细胞(CACs)的能力减弱有关,据推测,循环血管生成细胞参与内皮损伤修复。在这里,我们探讨了来自ED和心血管危险因素(vrf)但无临床动脉粥样硬化患者的人血清(HS)对培养的健康男性MNCs分化cac和形成菌落的影响。HS对CACS和菌落形成单位(cfu)数量的影响与循环内皮损伤标志物和血管生成调节剂有关。35例ED患者和10例健康男性的MNCs分别在标准条件下或20% HS中培养。在培养7天后,通过摄取乙酰化低密度脂蛋白并结合欧洲巨藻凝集素i来鉴定ccs。酶联免疫吸附试验评估血浆可溶性e-选择素、内皮素(ET)-1、组织型纤溶酶原激活剂(tPA)、血管内皮生长因子(VEGF)165和sVEGF受体(R)-1。与标准培养基相比,用HS培养MNCs后,健康男性的cac和cfu数量减少。与健康男性相比,VRF暴露较高或较低的ED患者的HS抑制作用明显更高。抑制作用与vrf暴露、ED严重程度、b超测量颈总动脉内膜中膜厚度呈正相关,与血浆se -选择素、sET-1和sVEGFR-1呈正相关。参与血管平衡的细胞功能障碍是由可溶性因子引起的,这些因子尚不清楚,但在ED和vrf患者的非常初始的系统性血管疾病中已经存在。
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引用次数: 13
Smaller genitals at school age in boys whose mothers were exposed to non-persistent pesticides in early pregnancy 母亲在怀孕早期接触非持久性杀虫剂的男孩在学龄期生殖器较小
Pub Date : 2012-03-06 DOI: 10.1111/j.1365-2605.2012.01252.x
C. Wohlfahrt-Veje, H. R. Andersen, T. K. Jensen, P. Grandjean, N. E. Skakkebæk, K. M. Main

Endocrine disrupting chemicals are believed to play a role in the development of the testicular dysgenesis syndrome. Many pesticides are known to have endocrine disrupting abilities. In a previous study, sons of women who were occupationally exposed to non-persistent pesticides in early pregnancy showed signs of impaired reproductive function (reduced genital size and altered serum hormone concentrations) at three months of age. To assess the possible long-term effects of prenatal pesticide exposure, the boys were re-examined at 6–11 years. The 94 boys (59 exposed, 35 unexposed) underwent genital examinations including ultrasound of testicular volumes, puberty staging (Tanner), anthropometry, and blood sampling. Only a few of the boys had reached puberty (n = 3). Among prepubescent boys, testicular volume and penile length (age- and weight-adjusted) were reduced if mothers were exposed to pesticides. The effects were associated with the maternal exposure levels, so that high-exposed boys had smaller genitals than medium-exposed boys, who had smaller genitals than those who were unexposed. Boys of mothers in the high exposure group (n = 23) had 24.7% smaller testes (95% CI: −62.2; −10.1) and 9.4% shorter penile length (95% CI: −16.8; −1.1) compared with the unexposed. The testicular volume and penile length at school age could be tracked to measures from the same boys made at 3 months, e.g. those that had small testes at school age also had small testes at 3 months. Pituitary and testicular hormone serum concentrations did not differ between exposed and unexposed boys. Eight prenatally exposed boys had genital malformations (no unexposed). These boys had smaller testis, shorter penile length and lower inhibin B concentrations than prepubertal boys without genital malformations. The findings support the results obtained at three months of age and indicate that prenatal pesticide exposure has long-term effects on reproductive function in boys.

内分泌干扰化学物质被认为在睾丸发育不良综合征的发展中起作用。众所周知,许多杀虫剂具有干扰内分泌的能力。在先前的一项研究中,在怀孕早期职业接触非持久性农药的妇女的儿子在三个月大时显示出生殖功能受损的迹象(生殖器尺寸缩小和血清激素浓度改变)。为了评估产前接触农药可能产生的长期影响,这些男孩在6-11岁时再次接受了检查。94名男孩(59名接触者,35名未接触者)接受了生殖器检查,包括睾丸体积超声、青春期分期(Tanner)、人体测量和血液采样。只有少数男孩进入了青春期(n = 3)。在青春期前的男孩中,如果母亲接触杀虫剂,睾丸体积和阴茎长度(经年龄和体重调整后)会减少。这种影响与母亲的暴露水平有关,因此高暴露男孩的生殖器比中等暴露男孩的生殖器小,中等暴露男孩的生殖器比未暴露男孩的生殖器小。高暴露组(n = 23)母亲的男孩有24.7%的小睾丸(95% CI: - 62.2;−10.1),阴茎长度缩短9.4% (95% CI:−16.8;−1.1)。学龄时的睾丸体积和阴茎长度可以追溯到同一男孩3个月时的测量结果,例如,学龄时睾丸小的男孩在3个月时睾丸也小。垂体和睾丸激素的血清浓度在暴露和未暴露的男孩之间没有差异。8名产前暴露的男孩有生殖器畸形(未暴露的没有)。这些男孩的睾丸较小,阴茎长度较短,抑制素B浓度低于青春期前无生殖器畸形的男孩。这一发现支持了三个月大时获得的结果,并表明产前接触农药对男孩的生殖功能有长期影响。
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引用次数: 34
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International journal of andrology
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