BACKGROUND & AIMS: :Varicocele is considered a predominantly unilateral left-sided disease. However, since male fertility is preserved with only one healthy testis, infertility perforce represents bilateral testicular dysfunction. It was hypothesized that: (i) right varicocele cannot be diagnosed by palpation and therefore has not been treated in the past by the traditional treatment, and (ii) right varicocele causes impaired oxygen supply in the right testicular microcirculation, leading to germ cell degeneration. This study performed venographies of both right and left internal spermatic veins during the treatment of 840 infertile men with varicocele and analysed the results using tools of fluid mechanics. Histopathology of the right testis revealed stagnation of blood flow and degenerative changes attributed to lack of adequate oxygenation in all testicular cell types. Right varicocele was found in the vast majority of the patients. We found that due to the destruction of one-way valves, pathologic hydrostatic pressure is produced in the testicular venous microcirculatory system about five times higher than normal, exceeding arteriolar pressure. The pressure gradient between the arterioles and venules in the testicular tissue is therefore reversed, leading to persistent hypoxia. Right varicocele, although undetected, is prevalent in infertile men with varicocele, hence only bilateral occlusion of the internal spermatic veins, including the associated bypasses, eliminating the pathologic hydrostatic pressure will lead to resumption of arterial blood flow in the testicular microcirculation.

背景与目标： : 精索静脉曲张被认为是一种主要的单侧左侧疾病。但是，由于只有一个健康的睾丸可以保留男性的生育能力，因此不育表现为双侧睾丸功能障碍。假设 :( i) 无法通过触诊来诊断右精索静脉曲张，因此过去没有通过传统疗法进行治疗，并且 (ii) 右精索静脉曲张会导致右睾丸微循环中的氧气供应受损，导致生殖细胞变性。这项研究在治疗840名患有精索静脉曲张的不育男性期间对左右精索内静脉进行了静脉造影，并使用流体力学工具分析了结果。右睾丸的组织病理学显示，由于所有睾丸细胞类型缺乏足够的氧合，导致血流停滞和退行性变化。在绝大多数患者中发现了右精索静脉曲张。我们发现，由于单向阀的破坏，睾丸静脉微循环系统中产生的病理性静水压力约为正常水平的五倍，超过了小动脉压力。因此，睾丸组织中小动脉和小静脉之间的压力梯度相反，导致持续的缺氧。右精索静脉曲张虽然未被发现，但在患有精索静脉曲张的不育男性中很普遍，因此只有双侧精索内静脉 (包括相关的旁路) 闭塞，消除病理性静水压将导致睾丸微循环中动脉血流的恢复。

BACKGROUND & AIMS: :The differential relative contribution of males and females from Africa and Europe to individual African American genomes is relevant to mapping genes utilizing admixture analysis. The assessment of ancestral population contributions to the four types of genomic DNA (autosomes, X and Y chromosomes, and mitochondrial) with their differing modes of inheritance is most easily addressed in males. A thorough evaluation of 93 African American males for 2,018 autosomal single nucleotide polymorphic (SNP) markers, 121 X chromosome SNPs, 10 Y chromosome haplogroups specified by SNPs, and six haplogroup defining mtDNA SNPs is presented. A distinct lack of correlation observed between the X chromosome and the autosomal admixture fractions supports separate treatment of these chromosomes in admixture-based gene mapping applications. The European genetic contributions were highest (and African lowest) for the Y chromosome (28.46%), followed by the autosomes (19.99%), then the X chromosome (12.11%), and the mtDNA (8.51%). The relative order of admixture fractions in the genomic compartments validates previous studies that suggested sex-biased gene flow with elevated European male and African female contributions. There is a threefold higher European male contribution compared with European females (Y chromosome vs. mtDNA) to the genomes of African American individuals meaning that admixture-based gene discovery will have the most power for the autosomes and will be more limited for X chromosome analysis.

背景与目标： : 非洲和欧洲的男性和女性对非裔美国人单个基因组的不同相对贡献与利用混合分析定位基因有关。在男性中，最容易解决祖先种群对四种类型的基因组DNA (常染色体，X和Y染色体以及线粒体) 及其不同遗传方式的贡献的评估。提出了对93名非洲裔美国男性的2,018个常染色体单核苷酸多态性 (SNP) 标记，121个X染色体SNP，10个由SNP指定的Y染色体单倍群以及6个定义mtDNA SNP的单倍群的全面评估。在X染色体和常染色体混合组分之间观察到的明显缺乏相关性支持在基于混合的基因作图应用中对这些染色体进行单独处理。欧洲对Y染色体的遗传贡献最高 (非洲最低) (28.46%)，其次是常染色体 (19.99%)，然后是X染色体 (12.11%) 和mtDNA (8.51%)。基因组区室中混合组分的相对顺序验证了先前的研究，这些研究表明，性别偏向的基因流具有较高的欧洲男性和非洲女性贡献。与欧洲女性相比，欧洲男性对非裔美国人个体基因组的贡献高出三倍 (Y染色体与mtDNA)，这意味着基于混合物的基因发现将对常染色体具有最大的力量，并且对X染色体分析。

BACKGROUND & AIMS: :As there are limitations to current methods of male contraception, research has been undertaken to develop hormonal contraceptives for men, analogous to the methods for women based on estrogen and progestogens. When testosterone is administered to a man, it functions as a contraceptive by suppressing the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary gland. Since these hormones are the main stimulatory signals for spermatogenesis, low levels of LH and FSH markedly impair sperm production. After 3-4 months of testosterone treatment, 60-70% of men no longer have sperm in their ejaculate, and most other men exhibit markedly diminished sperm counts. Male hormonal contraception is well tolerated, free of serious adverse side effects, and 95% effective in the prevention of pregnancy. Importantly, male hormonal contraception is reversible, with sperm counts usually recovering within 4 months of the discontinuation of hormone treatment. Because exogenous testosterone administration alone does not completely suppress sperm production in all men, researchers have combined testosterone with second agents, such as progestogens or gonadotropin-releasing-hormone antagonists, to further suppress secretion of LH and FSH and improve suppression of spermatogenesis. Recent trials have used combinations of long-acting injectable or implantable forms of testosterone with progestogens, which can be administered orally, by injection or by a long-acting implant. Such combinations suppress spermatogenesis to zero without severe side effects in 80-90% of men, with near-complete suppression in the remainder of individuals. One of these testosterone and progestogen combination regimens might soon bring the promise of male hormonal contraception to fruition.

背景与目标： : 由于目前男性避孕方法存在局限性，因此已经进行了研究以开发针对男性的激素避孕药，类似于基于雌激素和孕激素的女性避孕方法。当向男性施用睾丸激素时，它通过抑制垂体的促黄体激素 (LH) 和促卵泡激素 (FSH) 的分泌而起到避孕作用。由于这些激素是精子发生的主要刺激信号，因此低水平的LH和FSH明显损害了精子的产生。经过3-4个月的睾酮治疗后，60-70% 的男性射精中不再有精子，大多数其他男性的精子数量明显减少。男性激素避孕耐受性良好，无严重不良副作用，95% 有效预防妊娠。重要的是，男性激素避孕是可逆的，精子数量通常在停止激素治疗后4个月内恢复。由于单独使用外源性睾丸激素并不能完全抑制所有男性的精子产生，因此研究人员已将睾丸激素与第二种药物 (例如孕激素或促性腺激素释放激素拮抗剂) 结合使用，以进一步抑制LH和FSH的分泌并改善精子发生的抑制。最近的试验使用了长效可注射或可植入形式的睾丸激素与孕激素的组合，可以口服，注射或长效植入物给药。在80-90% 的男性中，这种组合将精子发生抑制为零，而没有严重的副作用，在其余个体中几乎完全抑制。这些睾丸激素和孕激素联合疗法之一可能很快就会实现男性激素避孕的希望。

BACKGROUND & AIMS: :A study was conducted to determine whether following exposure of male mice to high temperatures, the ability of their spermatozoa to fertilise ova was reduced, especially during the period before the males became completely infertile. Male mice placed in a microclimate chamber at 36 degrees C for two periods, each of 12 h on successive days, were less able to fertilise control females in vivo when mated and, even in those females that became pregnant, litter size was reduced. However, these effects were associated with falls in testis weight and numbers of spermatozoa in the testis and epididymis. To determine whether the effect on fertility was a result of the decreased spermatozoa numbers, spermatozoa were collected from the epididymides of heated and control males. Equal numbers of motile spermatozoa from an unselected sample or those subjected to a swim-up procedure to separate those that were motile from the immotile ones in the sample were then mixed in vitro with oocytes from superovulated normal females. Similar numbers of spermatozoa from both control and heated males bound to the zona pellucida but smaller percentages of the oocytes were fertilised by spermatozoa from the heated males and fewer of these spermatozoa penetrated the ova. The effects were first seen 7 days after the heat exposure and became more obvious after 10 or 14 days.

背景与目标： : 进行了一项研究，以确定雄性小鼠暴露于高温后，其精子受精卵子的能力是否降低，尤其是在雄性完全不育之前。在36摄氏度的小气候室中放置两个周期的雄性小鼠，每次连续12小时，交配时在体内受精对照雌性的能力较小，即使在怀孕的雌性中，产仔数也减少了。然而，这些影响与睾丸重量下降以及睾丸和附睾中精子数量下降有关。为了确定对生育力的影响是否是精子数量减少的结果，从加热和对照男性的附睾中收集了精子。然后将来自未选择样品的等量运动精子或经过游泳程序以将样品中运动的精子与未运动的精子分开的精子与超排卵正常雌性的卵母细胞在体外混合。与透明带结合的对照雄性和受热雄性的精子数量相似，但受热雄性的精子受精的卵母细胞百分比较小，而这些精子穿透卵子的数量较少。这种影响首先在暴露于热后7天出现，并在10或14天后变得更加明显。

BACKGROUND & AIMS: :A retrospective study of male breast cancer was undertaken at Ouagadougou University Teaching Hospital over a 3 year period (1993-1996). Authors report 5 cases representing 4.16% of all breast cancers. The patients' mean age was 61 years. The average duration of signs and symptoms before the diagnosis was 13 months. Clinically all the 5 cases presented advanced cancers (4 T4N2M0, 1 T4N2M1 according to UICC TNM System) with size ranging from 5.5, to 11.5 cm. Histology found: 2 medullary infiltrating carcinoma, 1 canalar infiltrating carcinoma, 1 colloid mucous carcinoma and 1 lobular infiltrating carcinoma. All patients had mastectomy associated with axillary clearance in 4 cases. Radiotherapy, chemotherapy and hormonotherapy were not associated because unavailable in Burkina Faso. Three patients died: the first, 10 days after surgical treatment and the 2 others respectively after 14 and 17 months. We have lost sight 1 patients. The last one is still alive. Authors find that to get better prognosis, it is important to improve medical and technical means, to increase information and to promote early detection.

背景与目标： : 在瓦加杜古大学教学医院进行了为期3年 (1993-1996年) 的男性乳腺癌回顾性研究。作者报告了5例代表所有乳腺癌4.16% 的病例。患者的平均年龄为61岁。诊断前症状和体征的平均持续时间为13个月。临床上所有5例均表现为晚期癌症 (根据UICC TNM系统，4个T4N2M0，1个T4N2M1)，大小从5.5到11.5厘米。组织学发现: 髓质浸润性癌2例，管内浸润性癌1例，胶体粘液性癌1例，小叶浸润性癌1例。所有患者均行乳房切除术伴腋窝清除4例。放疗，化疗和激素治疗不相关，因为在布基纳法索不可用。3例患者死亡: 手术治疗后第1、10天，另外2例分别在14和17个月后死亡。我们已经看不见1个病人了。最后一个还活着。作者发现，要获得更好的预后，必须改善医疗和技术手段，增加信息并促进早期发现。

BACKGROUND & AIMS: OBJECTIVE:Cross-sectional studies show that active individuals are leaner than their sedentary counterparts. The purpose of this paper is to determine the extent that this is due to self-selection bias, specifically to initially leaner men and women choosing to exercise longer and more intensely. METHODS:Walking quantity (weekly distance) and intensity (speed) were compared to current body mass index (BMI) (BMI(current)) and BMI at the start of walking (BMI(starting)) in 20,353 women and 5174 men who on average had walked regularly for exercise for 7.2 and 10.6 years, respectively. RESULTS:The relationships of both BMI(current) and BMI(starting) to both distance and intensity were nonlinear (convex). On average, BMI(starting) explained >70% of the association between BMI(current) and intensity, and 40 and 17% of the associations between BMI(current) and distance in women and men, respectively. Although the declines in BMI(current) with distance and intensity were greater among fatter individuals than leaner individuals, the portions attributable to BMI(starting) remained relatively constant regardless of fatness. Thus, self-selection bias accounted for most of the decline in BMI with walking intensity and smaller, albeit significant, proportions of the decline with distance. CONCLUSION:Although walking intensity and walking distance are both strongly associated with greater leanness, intensity is less likely to be causally related to leanness than is distance, and the latter should be encouraged for reversing or preventing weight gain.

背景与目标：

BACKGROUND & AIMS: :Male breast cancer (MBC) is an uncommon neoplasm that shares several biologic characteristics with its female counterpart. In the latter, abnormalities in the expression and/or copy number of the ERBB2 gene are present in 10% to 30% of invasive carcinoma and behave as poor prognostic markers. ERBB2 abnormalities have also been reported in MBC, yet at lower frequency, but their prognostic significance remains controversial. Furthermore, no study has addressed the impact of chromosome 17 abnormalities in MBC survival. In this study, the ERBB2-gene status (overexpression and amplification) and chromosome 17 numerical abnormalities were investigated in a series of 50 archival cases of MBC. The results, together with patient's age, histologic grade, pathologic stage, and estrogen receptor status were correlated with overall survival. ERBB2-protein overexpression was present in 7 cases (14%), ERBB2-gene amplification in 4 (8%), and aneuploidy of chromosome 17 in 12 cases (33.3%). The pathologic stage, ERBB2 overexpression and ERBB2 amplification were significantly correlated with overall survival (P=0.002, 0.016, and 0.009, respectively). No correlation was observed between chromosome 17 aneuploidy and overall survival. Therefore, despite their low incidence in MBC, expression abnormalities of ERBB2 behave, together with the pathologic stage of the tumor, as predictors of overall survival, akin to what has been reported for its female counterpart.

背景与目标： : 男性乳腺癌 (MBC) 是一种罕见的肿瘤，与女性具有多种生物学特征。在后者中，ERBB2基因的表达和/或拷贝数的异常存在于10% 浸润性癌的30% 中，并且表现为不良的预后标志物。在MBC中也有ERBB2异常的报道，但频率较低，但其预后意义仍存在争议。此外，还没有研究涉及17号染色体异常对MBC存活的影响。在这项研究中，在一系列50例MBC档案病例中研究了ERBB2-gene状态 (过表达和扩增) 和17号染色体数字异常。结果以及患者的年龄，组织学分级，病理分期和雌激素受体状态与总生存率相关。ERBB2-protein过表达7例 (14%)，ERBB2-gene扩增4例 (8%)，17号染色体非整倍性12例 (33.3%)。病理分期，ERBB2过表达和ERBB2扩增与总生存期显着相关 (分别为P = 0.002，0.016和0.009)。在17号染色体非整倍性与总生存率之间未观察到相关性。因此，尽管ERBB2在MBC中的发生率较低，但其表达异常与肿瘤的病理阶段一起表现为总体生存的预测指标，类似于已报道的女性对应物。

BACKGROUND & AIMS: BACKGROUND:Testosterone replacement in hypogonadal males improves body composition, sexual function, and health-related quality of life. Male cancer survivors are at risk of androgen deficiency; however, when and in whom testosterone should be replaced remain unanswered questions. OBJECTIVE:The aim of our study was to define the prevalence of androgen deficiency in this patient group through assessment of testosterone levels and related measures. DESIGN:This was a cross-sectional, observational study of cases and controls. We recruited 176 cancer survivors and 213 controls, aged 25-45 yr. RESULTS:Of cancer survivors, 97% had received chemotherapy and 40% radiotherapy. Cancer survivors had lower total testosterone (tT) levels than controls (mean difference 2.67 nmol/liter; 95% confidence interval 1.58-3.76; P = 0.003), and 24 of 176 (13.6%; 95% confidence interval 9.3-19.5) had a tT less than 10 nmol/liter, which was less than 2.5% centile for controls. Cancer survivors had a greater fat mass, higher fasting insulin and glucose levels, increased fatigue, and reduced sexual function and health-related quality of life. In both cohorts, the tT correlated negatively with insulin levels and negatively with body fat mass; however, the difference in tT between them was independent of fat mass. We measured tT and SHBG and calculated bioavailable testosterone. The changes in calculated bioavailable testosterone were similar to tT. CONCLUSIONS:A significant proportion of young male cancer survivors had a frankly low tT associated with an increased fat mass and insulin level compared with controls. These factors would be predicted to improve in response to testosterone replacement therapy and provide a powerful argument for an interventional study of testosterone therapy in young male cancer survivors.

背景与目标：

BACKGROUND & AIMS: :Y-autosomal translocation has been previously reported in association with male infertility; however, the mechanisms of Y-autosomal translocation and non‑obstructive azoospermia or severe oligospermia remain unclear. G‑banding and fluorescence in situ hybridization (FISH) were performed to analyze the translocation of chromosomes, and a single nucleotide polymorphism (SNP) genotyping assay was used to test mutations. The present study describes three new cases with a de novo balanced translocation t(Y;13), t(Y;9) and t(Y;6). To further explore the genotype‑phenotype correlation, G‑banding and FISH were performed and indicated the presence of a derivative chromosome. The SNP genotyping assay using a microarray revealed no abnormality, especially in the Y chromosome. Molecular deletion analysis demonstrated that no microdeletion was detected in the azoospermia factor region of the Y chromosome in the examined, infertile men. Based on these observations, the authors proposed the hypothesis that a position effect involving unknown spermatogenesis regulatory gene(s) serves a key role in male infertility.

背景与目标： : Y常染色体易位与男性不育有关。但是，Y常染色体易位和非阻塞性无精子症或严重少精子症的机制尚不清楚。进行g-带和荧光原位杂交 (FISH) 以分析染色体的易位，并使用单核苷酸多态性 (SNP) 基因分型分析来测试突变。本研究描述了三个从头平衡易位t(Y;13)，t(Y;9) 和t(Y;6) 的新病例。为了进一步探索基因型表型的相关性，进行了g-带和FISH，并指出存在衍生染色体。使用微阵列的SNP基因分型分析未显示异常，尤其是在Y染色体中。分子缺失分析表明，在被检查的不育男性中，在Y染色体的无精子因子区域中未检测到微缺失。基于这些观察结果，作者提出了以下假设: 涉及未知精子发生调节基因的位置效应在男性不育中起关键作用。

BACKGROUND & AIMS: :149 cases of urethral stricture were treated in the Urology Department from 1971 to 1984. All of these patients have therefore been treated with a minimal follow-up of 5 years. There were 87 cases of post-traumatic stricture, 53 of whom were lost to follow-up during the survey, 8 died and 26 patients were able to be reviewed. The remaining 62 cases consisted of post-infectious strictures, with 37 patients lost to follow-up during the survey, 1 patient who died and 24 patients who were reviewed. The patients reviewed were assessed according to the criteria of the SFU (French Urology Society) survey. Direct vision internal urethrotomy was performed in 33 cases with 18 very good or good results (54%), segmental resection was performed in 10 cases with 7 very good or good results, urethroplasty was performed in 4 cases with 2 good results and 2 urethral dilatations were performed with 2 good results. The failures were essentially treated by more complex surgery (urethroplasty).

背景与目标： : 泌尿科1971年1984年治疗尿道狭窄149例。因此，所有这些患者均接受了5年的最小随访。外伤性狭窄87例，其中53例在调查中失访，8例死亡，26例患者得以复查。其余62例为感染后狭窄，其中37例患者在调查中失访，1例死亡，24例患者接受复查。根据SFU (法国泌尿外科学会) 调查的标准对患者进行评估。33例行直视内尿道切开术，18例效果非常好或良好 (54%)，10例行节段切除术，7例效果非常好或良好，4例行尿道成形术，2例尿道扩张，2例效果良好。这些失败基本上是通过更复杂的手术 (尿道成形术) 治疗的。

BACKGROUND & AIMS: BACKGROUND:Semen quality, a predictor of male fertility, has been suggested declining worldwide. Among other life style factors, male coffee/caffeine consumption was hypothesized to influence semen parameters, but also sperm DNA integrity. To summarize available evidence, we performed a systematic review of observational studies on the relation between coffee/caffeine intake and parameters of male fertility including sperm ploidy, sperm DNA integrity, semen quality and time to pregnancy. METHODS:A systematic literature search was performed up to November 2016 (MEDLINE and EMBASE). We included all observational papers that reported the relation between male coffee/caffeine intake and reproductive outcomes: 1. semen parameters, 2. sperm DNA characteristics, 3. fecundability. All pertinent reports were retrieved and the relative reference lists were systematically searched in order to identify any potential additional studies that could be included. RESULTS:We retrieved 28 papers reporting observational information on coffee/caffeine intake and reproductive outcomes. Overall, they included 19,967 men. 1. Semen parameters did not seem affected by caffeine intake, at least caffeine from coffee, tea and cocoa drinks, in most studies. Conversely, other contributions suggested a negative effect of cola-containing beverages and caffeine-containing soft drinks on semen volume, count and concentration. 2. As regards sperm DNA defects, caffeine intake seemed associated with aneuploidy and DNA breaks, but not with other markers of DNA damage. 3. Finally, male coffee drinking was associated to prolonged time to pregnancy in some, but not all, studies. CONCLUSIONS:The literature suggests that caffeine intake, possibly through sperm DNA damage, may negatively affect male reproductive function. Evidence from epidemiological studies on semen parameters and fertility is however inconsistent and inconclusive. Well-designed studies with predefined criteria for semen analysis, subject selection, and life style habits definition, are essential to reach a consistent evidence on the effect of caffeine on semen parameters and male fertility.

背景与目标：

BACKGROUND & AIMS: :It is commonly believed that hybridization might lead to the formation of new polyploidy species, but it is unclear whether hybridization can produce a new homodiploid species. Here, we report the spontaneous occurrence of a new crucian carp-like homodiploid fish (2n = 100) that originated from the interspecific hybridization of female common carp (Cyprinus carpio, Cyprininae, 2n = 100) × male blunt snout bream (Megalobrama amblycephala, Cultrinae, 2n = 48). The phenotype and reproductive traits of this new crucian carp-like homodiploid fish were found to be very similar to those of the existing diploid species (diploid crucian carp; Carassius auratus). FISH and 5S rDNA analyses revealed that the genotype of the crucian carp-like homodiploid fish differs from those of its parents but is closely related to that of diploid crucian carp. The results provide evidence of the existence of a possible route through which the distant hybridization of this cross can generate crucian carp. The new type of homodiploid fish is of great value in fish genetic breeding and for studying the early evolutionary process.

背景与目标： : 通常认为杂交可能导致形成新的多倍体物种，但目前尚不清楚杂交是否可以产生新的同二倍体物种。在这里，我们报道了一种新的鲫鱼样同二倍体鱼 (2n   =   100) 的自发发生，该鱼起源于雌性鲤鱼的种间杂交 (Cyprinus carpio，cyprinininae，2n   =   100) ×  雄性钝吻鲷 (Megalobrama amblycephala，Cultrinae，2n   =   48)。发现这种新的cru鱼状同二倍体鱼类的表型和繁殖性状与现有的二倍体物种 (二倍体cru鱼; Car鱼) 非常相似。FISH和5S rDNA分析表明，cru鱼样同二倍体鱼的基因型与其亲本不同，但与二倍体cru鱼的基因型密切相关。结果提供了证据，表明存在一种可能的途径，通过该途径，该杂交的远距离杂交可以产生cru鱼。新型同二倍体鱼类在鱼类遗传育种和早期进化过程研究中具有重要价值。

BACKGROUND & AIMS: :We have previously demonstrated that gonadectomy either prior to (early) or after (late) puberty elevated ethanol consumption in males to levels similar to intact adult females-effects that were attenuated by testosterone replacement. To assess whether alterations in the aversive effects of ethanol might contribute to gonadectomy-associated increases in ethanol intake in males, the present study examined the impact of gonadectomy on conditioned taste aversions (CTA) to ethanol in male and female Sprague-Dawley rats. Animals were gonadectomized, received sham surgery (SH) or non-manipulated (NM) on postnatal (P) day 23 (early) or 67 (late) and tested for CTA to ethanol in adulthood. Water-deprived rats were given 1 hr access every-other-day to 10% sucrose followed by an injection of ethanol (0, 1g/kg) for 5 test sessions. Test data were analyzed to determine the first day significant aversions emerged in each ethanol group (i.e., sucrose intakes significantly less than their saline-injected counterparts). Early gonadectomized males acquired the CTA more rapidly than did early SH and NM males (day 1 vs 3 and 4 respectively), whereas a gonadectomy-associated enhancement in ethanol CTA was not evident in late males. Among females, gonadectomy had little impact on ethanol-induced CTA, with females in all groups showing an aversion by the first or second day, regardless of surgery age. These data suggest that previously observed elevations in ethanol intake induced by either pre- or post-pubertal gonadectomy in males are not related simply to gonadectomy-induced alterations in the aversive effects of ethanol indexed via CTA.

背景与目标： : 我们以前已经证明，在青春期 (早期) 或青春期 (晚期) 之前进行性腺切除术会将男性的乙醇消耗量提高到与完整的成年女性相似的水平-睾丸激素替代作用会减弱。为了评估乙醇的厌恶作用的改变是否可能导致男性性腺切除术相关的乙醇摄入量增加，本研究检查了性腺切除术对雄性和雌性Sprague-Dawley大鼠对乙醇的条件性味厌恶 (CTA) 的影响。在出生后第23天 (早期) 或第67天 (晚期) 对动物进行性腺切除，接受假手术 (SH) 或非操纵 (NM)，并在成年后测试CTA至乙醇。每隔一天给缺水的大鼠1小时10% 蔗糖，然后注射乙醇 (0,1 g/kg) 进行5次测试。分析测试数据以确定每个乙醇组中出现的第一天明显厌恶 (即，蔗糖摄入量明显少于注射盐水的对应物)。早期性腺切除的男性获得CTA的速度比早期SH和NM的男性更快 (分别为第1天和第3天和第4天)，而在晚期男性中，性腺切除术相关的乙醇CTA增强并不明显。在女性中，性腺切除术对乙醇诱导的CTA几乎没有影响，无论手术年龄如何，所有组的女性在第一天或第二天都表现出厌恶情绪。这些数据表明，先前观察到的男性青春期前或青春期后性腺切除术引起的乙醇摄入量升高与性腺切除术引起的通过CTA索引的乙醇厌恶作用的改变无关。

BACKGROUND & AIMS: BACKGROUND:Vaginal candidiasis is frequent among pregnant women and it is treated with anti-fungal medication (conazoles). Conazoles have anti-androgenic properties and prenatal exposure in rodents is associated with a shorter (less masculine) anogenital distance (AGD) in male offspring. To our knowledge this has never been studied in humans. METHOD:In the Odense Child Cohort pregnant women residing in Odense municipality, Denmark, were recruited at gestational age 8-16 weeks between 2010 and 2012. Of the eligible 2421 mother-child pairs, 812 mother-son pairs were included. Questionnaire data on medicine use were collected in first and third trimester and physical examination at age 3 month was performed. Ano-scrotal distance; measured from the centre of anus to the posterior base of scrotum (AGDas). Ano-cephalad distance; measured from the centre of anus to the cephalad insertion of the penis (AGDap) and penile width; measured at the base of the penis. RESULTS:Eighty seven women had used antifungal medicine during pregnancy. Maternal use of oral fluconazole (n = 4) was associated with a 6.4 mm shorter AGDas (95% CI: -11.9;-0.9) in the male offspring. Use of antifungal vaginal tablets (n = 21), was associated with a non-significantly shorter AGDas (-1.9 mm; 95% CI: -4.3; 0.5) whereas exposure to vaginal cream (n = 23) was not associated to AGDas. Use of antifungal medicine in the window of genital development between 8 and 14 weeks of gestation was associated with a larger reduction in AGDas than exposure outside this window. Antifungal medicine intake was not associated with AGDap and penil width. CONCLUSION:Our preliminary findings prompted us to hypothesize that maternal use of conazole antifungal medication during pregnancy may affect the masculinization of male offspring. If confirmed, pregnant women should be advised to use antifungal medicine with caution.

背景与目标：

BACKGROUND & AIMS: :In the present study, we investigated the effects of repeated morphine pre-treatment on impairment of spatial memory acquisition induced by intra dorsal hippocampus (intra-CA1) administration of the non-selective cannabinoid CB1/CB2 receptor agonist, WIN55,212-2 in adult male rats. 2-day version of Morris water maze task has been used for the assessment of spatial memory. On the training day, rats were trained by a single training session of eight trials and 24 h later a probe trial test consist of 60s free swim period without a platform and the visible test was administered. Animals received pre-treatment subcutaneous (s.c.) injections of morphine, once daily for three days followed by five days drug-free treatment before training trials. The results indicated that bilateral pre-training intra-CA1 infusions of WIN55,212-2 (0.25 and 0.5 μg/rat) impaired acquisition of spatial memory on the training and test day. The amnesic effect of WIN55, 212-2 (0.5 μg/rat) was prevented in rats previously injected with morphine (20 mg/kg/day × 3 days, s.c.). Improvement in spatial memory acquisition in morphine-pretreated rats was inhibited by once daily administration of naloxone (1 and 2 mg/kg, s.c.) 15 min prior to injection of morphine for three days. The results suggest that sub-chronic morphine treatment may produced sensitization to cannabinoids, which in turn reversed the impairment of spatial memory acquisition induced by WIN55,212-2 and mu- opioid receptors may play an important role in this effect.

背景与目标： : 在本研究中，我们研究了重复吗啡预处理对非选择性大麻素CB1/CB2受体激动剂WIN55、212-2在成年雄性大鼠中给予背海马 (intra-CA1) 引起的空间记忆获取障碍的影响。莫里斯水迷宫任务的2天版本已用于评估空间记忆。在训练当天，对大鼠进行了八次试验的单次训练，24小时后进行了一次探针试验测试，该试验包括60s的自由游泳期，没有平台，并进行了可见测试。动物接受治疗前皮下注射吗啡，每天一次，持续三天，然后在训练试验前进行五天的无药治疗。结果表明，在训练和测试当天，双侧训练前intra-CA1输注WIN55，212-2 (0.25和0.5 μ g/大鼠) 会损害空间记忆的获取。在先前注射吗啡 (20 mg/kg/天 × 3天，s.C.) 的大鼠中预防WIN55，212-2 (0.5 μ g/大鼠) 的遗忘作用。每天服用一次纳洛酮 (1和2 mg/kg，s.C.) 可抑制吗啡预处理大鼠空间记忆的获取。注射吗啡前15分钟，持续三天。结果表明，亚慢性吗啡治疗可能会产生对大麻素的敏感性，从而逆转由WIN55，212-2和mu-阿片受体引起的空间记忆获取障碍可能在这种作用中起重要作用。