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Journal Of Andrology[JOURNAL]

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Circulating endothelial cells as marker of endothelial damage in male hypogonadism.

Milardi D, Grande G, Giampietro A … +8 more , Vendittelli F, Palumbo S, Tartaglione L, Marana R, Pontecorvi A, de Marinis L, Zuppi C, Capoluongo E

J Androl · 2012 · PMID 22700760 · Publisher ↗

Testosterone deficiency has become a frequently diagnosed condition in today's society affected by epidemic obesity, and is associated with cardiovascular risk. Recent studies have established the importance of altered v... Testosterone deficiency has become a frequently diagnosed condition in today's society affected by epidemic obesity, and is associated with cardiovascular risk. Recent studies have established the importance of altered vascular endothelium function in cardiovascular disease. The damage to the endothelium might also cause endothelial cell detachment, resulting in increased numbers of circulating endothelial cells (CEC) within the bloodstream. To evaluate whether hypogonadism could modify CEC count in peripheral bloodstream, we investigated peripheral blood CEC count using the CellSearch System, a semiautomatic method to accurately and reliably enumerate CECs, which are sorted based on a CD146(+), CD105(+), DAPI(+), CD45(-) phenotype, in a population of 20 patients with hypogonadism. The control group comprised 10 age- and sex-matched healthy participants. CEC count per milliliter was significantly increased in patients with hypogonadism vs the control group. In the group with hypogonadism, an inverse exponential correlation was present between testosterone levels and CEC count per milliliter. A direct linear correlation was present between waist circumference and CECs and between body mass index and CECs. The regression analysis showed that testosterone was the significant independent determinant of CECs. Our results underline that male hypogonadism is associated with endothelial dysfunction. The correlation between CEC and waist circumference underlines that visceral obesity may be synergically implicated in this regulation. Future studies are required to unveil the mechanisms involved in the pathogenesis of testosterone-induced endothelial disfunction, which may provide novel therapeutic targets to be incorporated in the management of hypogonadism.

Comparison of the results and complications of retroperitoneal, microsurgical subinguinal, and high inguinal approaches in the treatment of varicoceles.

Shiraishi K, Oka S, Ito H … +1 more , Matsuyama H

J Androl · 2012 · PMID 22700759 · Publisher ↗

The simplicity of the surgical procedure, as well as the high rate of success and low rate of complications, is of particular importance for varicocelectomies. We compared operative parameters, complication rates, and sp... The simplicity of the surgical procedure, as well as the high rate of success and low rate of complications, is of particular importance for varicocelectomies. We compared operative parameters, complication rates, and sperm parameters after retroperitoneal, microsurgical subinguinal and high inguinal varicocelectomy approaches in infertile men with varicoceles. This study included 307 infertile men with left varicoceles who underwent varicocelectomy by the retroperitoneal (n = 43), microsurgical subinguinal (n = 107), or high inguinal (n = 157) approach. The operative time was shorter for the retroperitoneal approach (29 minutes) compared with the microsurgical approaches and was significantly shorter for the high inguinal approach (52 minutes) compared with the subinguinal approach (66 minutes). Pain, as assessed by a visual analogue scale, and the use of nonsteroidal anti-inflammatory drugs were greatest following the retroperitoneal approach and significantly preferable following the high inguinal compared with the subinguinal approach. Recurrence/hydrocele was observed in 9.3%/9.3%, 0.9%/0.9%, and 1.3%/0.6% of patients after use of the retroperitoneal, subinguinal, and high inguinal approaches, respectively. Significant postoperative improvements in sperm concentration and motility were observed after all approaches, but such improvements were observed sooner and showed higher sperm concentration and motility after the use of the microsurgical approaches. Both microsurgical subinguinal and high inguinal approaches yielded comparable success rates, but the operative time and pain control were superior with the high inguinal approach. Because of its favorable safety profile, the microsurgical high inguinal approach should be of value to both experienced microsurgeons and trainees.

Nandrolone, an anabolic steroid, stabilizes Numb protein through inhibition of mdm2 in C2C12 myoblasts.

Liu XH, Yao S, Levine AC … +7 more , Kirschenbaum A, Pan J, Wu Y, Qin W, Collier L, Bauman WA, Cardozo CP

J Androl · 2012 · PMID 22700758 · Publisher ↗

Nandrolone, an anabolic steroid, slows denervation atrophy of rat muscle, prevents denervation-induced nuclear accumulation of intracellular domain of the Notch receptor, and elevates expression of Numb. Numb acts as an... Nandrolone, an anabolic steroid, slows denervation atrophy of rat muscle, prevents denervation-induced nuclear accumulation of intracellular domain of the Notch receptor, and elevates expression of Numb. Numb acts as an inhibitor of Notch signaling and promotes myogenic differentiation of satellite cells. Turnover of Numb is regulated by mdm2, an E3 ubiquitin ligase. With these considerations in mind, we investigated the effects of nandrolone on the expression of Numb and mdm2 proteins and determined the effect of mdm2 on nandrolone-induced alterations in Numb protein in C2C12 myoblasts. When C2C12 cells were cultured in a medium favoring differentiation (Dulbecco modified Eagle medium containing 2% horse serum), nandrolone up-regulated Numb protein levels in a time-dependent manner and prolonged Numb protein half-life from 10 to 18 hours. In contrast, nandrolone reduced the expression of mdm2 protein. To determine whether the decreased mdm2 expression induced by nandrolone was responsible for the increased levels and prolonged half-life of Numb protein in this cell line, mdm2-small interfering RNA (siRNA) was employed to inhibit mdm2 expression. Compared to cells transfected with scrambled siRNA (negative control), transfection with mdm2-siRNA increased basal Numb protein expression but abolished the further increase in Numb protein levels by nandrolone. In addition, transfection of mdm2-siRNA mimicked the effect of nandrolone to prolong the half-life of Numb protein. Moreover, when C2C12 cells were forced to overexpress mdm2, there was a significant decline in the expression of both basal and inducible Numb protein. Our data suggest that nandrolone, by a novel mechanism for this agent in a muscle cell type, increases Numb protein levels in C2C12 myoblasts by stabilizing Numb protein against degradation, at least in part, via suppression of mdm2 expression.

Evaluation of testicular sperm CRISP2 as a potential target for contraception.

Muñoz MW, Ernesto JI, Bluguermann C … +4 more , Busso D, Battistone MA, Cohen DJ, Cuasnicú PS

J Androl · 2012 · PMID 22653965 · Publisher ↗

Cysteine-rich secretory protein 2 (CRISP2) is a testicular sperm protein proposed to be involved in fertilization. With the aim of examining the relevance of CRISP2 for fertility and its potential use as a target for con... Cysteine-rich secretory protein 2 (CRISP2) is a testicular sperm protein proposed to be involved in fertilization. With the aim of examining the relevance of CRISP2 for fertility and its potential use as a target for contraception, in the present work, male and female rats were immunized with recombinant CRISP2 coupled to maltose-binding protein (MBP) and evaluated for their subsequent fertility. As controls, animals were injected with either MBP or recombinant CRISP1. Enzyme-linked immunosorbent assay of sera collected at different intervals after immunization indicated that CRISP2 immunization raised specific antibodies in both sexes, with levels that increased as a function of time. Western blot studies revealed that anti-CRISP2 sera were capable of recognizing CRISP2 in testicular, epididymal, and sperm extracts, whereas histological studies showed no evidence of autoimmune orchitis or epididymitis. Indirect immunofluorescence experiments revealed the ability of anti-CRISP2 sera to recognize the native sperm protein in fresh, capacitated, and ionophore-induced acrosome-reacted cells. Moreover, anti-CRISP2 sera significantly inhibited the sperm ability to penetrate zona-free eggs, confirming the role of CRISP2 in rat gamete fusion. In spite of the presence of circulating anti-CRISP2 antibodies capable of inhibiting the sperm fertilizing ability, mating studies revealed no effects of CRISP2 immunization on male or female fertility, in contrast to the significant inhibition observed in both sexes in animals injected with CRISP1. Together, these observations indicated the immunogenic properties of testicular CRISP2 but do not support CRISP2 as a target for immunocontraception or as a molecule responsible for generating autoimmune orchitis or immunoinfertility.

NADPH oxidase activation: a mechanism of erectile dysfunction in a rat model of sleep apnea.

Liu K, Liu XS, Xiao L … +4 more , Shang J, Li MC, Xu YJ, Liu HG

J Androl · 2012 · PMID 22653964 · Publisher ↗

Erectile dysfunction (ED) is a frequent occurrence in male patients with obstructive sleep apnea syndrome (OSAS). Long-term intermittent hypoxia (LTIH), one of the hallmarks of OSAS, could mediate ED. The objective of th... Erectile dysfunction (ED) is a frequent occurrence in male patients with obstructive sleep apnea syndrome (OSAS). Long-term intermittent hypoxia (LTIH), one of the hallmarks of OSAS, could mediate ED. The objective of this study was to test the hypothesis that increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity contributes to ED in rat responses to LTIH. Healthy male Sprague-Dawley rats were randomly distributed into 4 groups: a LTIH group, an apocynin (a selective NADPH oxidase inhibitor)-treated LTIH group, a sham LTIH group, and an apocynin-treated sham group. Erectile function was examined by measuring the mean arterial blood pressure (MAP) and intracavernosal pressure (ICP) on electrical stimulation of the cavernous nerve. Real-time quantitative polymerase chain reaction and Western blot were used to examine mRNA and protein expression of NADPH oxidase subunit in corpus cavernosa (CC). The level of malondialdehyde and superoxide dismutase were detected by colorimetry. Nitric oxide synthase (NOS) isoforms in CC were also investigated. LTIH markedly attenuated the erectile responses (ICP/MAP), and these were partially prevented by apocynin treatment. Promoted oxidative stress-associated NADPH oxidase subunit activation was found in CC from LTIH rats. Decreased expression and activity of constitutive NOS (cNOS), including endothelial NOS and neuronal NOS, associated with enhanced inducible NOS (iNOS) expression and activity were observed in LTIH rats. Apocynin prevented the decrease in cNOS activity and inhibited iNOS expression and activity in LTIH rats. These results indicate that NADPH oxidase activation plays an important role in the pathogenesis of LTIH-mediated ED.

Effect of a 60-day oral gavage of a crude alkaloid extract from Chromolaena odorata leaves on hormonal and spermatogenic indices of male rats.

Yakubu MT

J Androl · 2012 · PMID 22653963 · Publisher ↗

The present study was aimed at investigating the effects of the crude alkaloids isolated from Chromolaena odorata leaves on the hormonal and spermatogenic indices of male rats. The alkaloids obtained from C odorata leave... The present study was aimed at investigating the effects of the crude alkaloids isolated from Chromolaena odorata leaves on the hormonal and spermatogenic indices of male rats. The alkaloids obtained from C odorata leaves using standard methods were administered to male rats for 60 days at the doses of 250, 500, and 1000 mg/kg body weight. Thin-layer chromatographic analysis of the alkaloid mixture produced 8 spots, 3 of which were alkaloids with R(f) values of 0.41, 0.49, and 0.55 as confirmed by the formation of orange color and creamy precipitates with both Dragendorff and Mayer reagents, respectively. The alkaloids were represented in the extract by a yield of 20.28 g, corresponding to a percentage yield of 90.05% of the total extract of 22.52 g. The final body weights of both the control and alkaloid-treated animals increased significantly (P < .05) compared with their respective body weights before treatment. The alkaloids significantly decreased (P < .05) the testes-body weight ratio; the concentrations of testicular total protein, glycogen, sialic acid, and cholesterol; and the activities of γ-glutamyl transferase, acid phosphatase, and alkaline phosphatase. The serum luteinizing hormone and follicle-stimulating hormone levels, as well as testicular and serum testosterone levels, also decreased significantly (P < .05). There were decreases in the sperm count, motility, and density, as well as morphological changes in the sperm cells. The pH and whitish-gray color of the semen were not significantly affected. All of the doses of the alkaloids increased the total mean number of sperm cell abnormalities, with the secondary type predominating over the primary sperm cell abnormality. The alterations in the levels of the hormones and secretory and synthetic constituents of the testes and the spermatotoxic effects by the alkaloids from C odorata leaves may be due to nonavailability or deprivation of testosterone to the target organ. This lack of testosterone may have consequential effects on the reproductive process of the male rat.

Penile veins are the principal component in erectile rigidity: a study of penile venous stripping on defrosted human cadavers.

Hsu GL, Hung YP, Tsai MH … +5 more , Hsieh CH, Chen HS, Molodysky E, Huynh CC, Yu HJ

J Androl · 2012 · PMID 22604630 · Publisher ↗

The human erectile mechanism is an intricate interplay of hormonal, vascular, neurological, sinusoidal, pharmacological, and psychological factors. However, the relative influence of each respective component remains som... The human erectile mechanism is an intricate interplay of hormonal, vascular, neurological, sinusoidal, pharmacological, and psychological factors. However, the relative influence of each respective component remains somewhat unclear, and merits further study. We investigated the role of venous outflow in an attempt to isolate the key determinant of erectile function. Dynamic infusion cavernosometry and cavernosography was conducted on 15 defrosted human cadavers, both before and after the systematic removal and ligation of erection-related penile veins. Preoperatively, an infusion rate of more than 28.1 mL/min (from more than 14.0 to 85.0 mL/min) was required to induce a rigid erection (defined as intracavernosal pressure [ICP] exceeding 90 mmHg). Following surgery, we were able to obtain the same result at a rate of 7.3 mL/min (from 3.1 to 13.5 mL/min) across the entire sample. Thus, we witnessed statistically significant postoperative differences (all P ≤ .01), consistently elevated ICP, lower perfusion volumes, and a general reduction in time taken to attain rigidity. The cavernosograms provided further evidence substantiating the critical role played by erection-related veins, whereas histological samples confirmed the postoperative integrity of the corpora cavernosa. Given that our use of cadavers eliminated the influence of hormonal, arterial, neurological, sinusoidal, pharmacological, and psychological factors, we believe that our study demonstrates that the human erection is fundamentally a mechanical event contingent on venous competence.

Free nerve ending density on skin extracted by circumcision and its relation to premature ejaculation.

Malkoc E, Ates F, Tekeli H … +3 more , Kurt B, Turker T, Basal S

J Androl · 2012 · PMID 22604629 · Publisher ↗

Many studies have shown that skin tissue extracted by circumcision can cause differences in sexual function, especially at the time of ejaculation. Sensitivity changes in penile skin and sexual satisfaction deriving from... Many studies have shown that skin tissue extracted by circumcision can cause differences in sexual function, especially at the time of ejaculation. Sensitivity changes in penile skin and sexual satisfaction deriving from circumcision starting from premature ejaculation (PE) are discussed. Furthermore, most of these studies rely on questionnaires. Extracted free nerve endings (FNE) on the foreskin, which can detect temperature, mechanical stimuli (touch, pressure, stretch) or pain (nociception), have not been researched. Our aim is to determine FNEs in foreskin and the affects on sexual function, especially PE. This prospective study was done on adults who voluntarily applied to be circumcised between September 2010 and October 2011. The ejaculation latency times (ELT) before circumcision have been assessed, and a PE diagnostic tool (PEDT) form was filled out by the urologist according to the answers given by the volunteers. The proximal and distal ends of the foreskin were marked before circumcision, and the extracted foreskin was sent to the pathology department to determine FNEs. Twenty volunteers (average age 21.25 ± 0.44 years) were included in the study. The average ELT was 103.55 ± 68.39 seconds, and the average PE score was 4.35 ± 3.13. Proximal, middle, and distal tip nerve densities were compared. Proximal and distal (P = .003) and proximal and middle (P = .011) segments differed from each other, whereas middle and distal were similar (P = .119). There were not any correlations between PEDT scores and total nerve endings number (r = .018, P = .942). Also there were not any correlations between mean ELT and PEDT scores (r = .054, P = .822). The tissue extracted by circumcision has intensive FNEs, yet FNE intensity has no relation to PE.

A simplified approach to assessing penile endothelial function in young individuals at risk of erectile dysfunction.

Wu HT, Lee CH, Chen CJ … +2 more , Tsai IT, Sun CK

J Androl · 2012 · PMID 22604628 · Publisher ↗

Erectile dysfunction (ED) reflects a risk for systemic cardiovascular diseases by virtue of a common etiology of vascular endothelial dysfunction, which is increasingly reported to affect young adults. On the basis of ph... Erectile dysfunction (ED) reflects a risk for systemic cardiovascular diseases by virtue of a common etiology of vascular endothelial dysfunction, which is increasingly reported to affect young adults. On the basis of physiological phenomenon of reactive hyperemia (RH), systemic and penile endothelial functions in healthy young adults were compared with the use of digital data on arterial waveforms before and after RH induction. Between July 2009 and March 2011, 32 young adult volunteers with normal erectile functions were recruited. Questionnaires on medical histories and sexual functions and blood samples for testosterone and biochemical analyses were obtained. Dilatation index (DI) and penile arterial waveform amplitude (PAWA) ratios for assessing systemic and penile endothelial function were acquired with an air pressure sensing system on the arm and a penile arterial waveform analyzing system on the penis, respectively. A total cholesterol/high-density lipoprotein (TC/HDL) ratio greater than 4.1 was used to define high risk for ED. Remarkable positive correlation was noted between DI and PAWA ratio (r = .640, P < .001). DI showed significant positive associations with serum testosterone (P = .012) and serum HDL level, whereas it showed negative correlations with total triglyceride and glycosylated hemoglobulin levels, body weight, waist circumference, body mass index, and diastolic blood pressure. Similarly, the PAWA ratio showed significant positive correlations with serum testosterone (P < .001) and HDL levels, but negative associations with body weight, waist circumference, and body mass index. Both DI and PAWA ratio successfully identified participants at high risk for ED (eg, TC/HDL ratio > 4.1; P < .05). Our results demonstrated that penile endothelial function can be assessed by evaluating systemic endothelial function in young healthy adults for early identification of risk for ED.

Association between sex steroid hormones and hematocrit in a nationally representative sample of men.

Paller CJ, Shiels MS, Rohrmann S … +5 more , Menke A, Rifai N, Nelson WG, Platz EA, Dobs AS

J Androl · 2012 · PMID 22604627 · Full text

Low or high hematocrit levels are associated with increased morbidity and mortality, mediated via anemia or thromboembolic events, respectively. It is therefore important to identify factors that influence hematocrit. Al... Low or high hematocrit levels are associated with increased morbidity and mortality, mediated via anemia or thromboembolic events, respectively. It is therefore important to identify factors that influence hematocrit. Although androgens are known to stimulate hematopoietic cells, it is unknown whether circulating sex steroid hormones affect hematocrit. The association between serum sex steroid hormone concentrations and hematocrit in men aged ≥ 20 years was evaluated in a cross-sectional study of 1273 men in the Third National Health and Nutrition Examination Survey (1988-1991). Outcomes were low (<10th percentile), high (>90th percentile), and mean hematocrit. Men with low free testosterone levels had a lower hematocrit than men with normal free testosterone levels (P = .03), although no relationship was found between total testosterone level and hematocrit. The relationship between sex hormone-binding globulin (SHBG) and hematocrit was complex, with both low (P < .001) and high (P = .01) SHBG levels associated with lower hematocrit in men aged ≥ 20 years and only high (P = .01) SHBG levels in men aged ≥ 50 years. The odds ratio (OR) of high vs normal hematocrit increased as total estradiol (OR, 2.84; P trend = .04) and free estradiol (OR, 2.23; P trend = .09) levels increased. In this nationally representative study of men, sex steroid hormone levels, particularly low free testosterone and high SHBG levels, were associated with lower hematocrit, and high total and free estradiol levels were associated with high hematocrit. Thus, changes in sex hormone levels with aging may contribute to the increased prevalence of anemia and thromboembolic stroke in men as they age.

Erectile dysfunction and extramarital sex induced by timed intercourse: a prospective study of 439 men.

Bak CW, Lyu SW, Seok HH … +4 more , Byun JS, Lee JH, Shim SH, Yoon TK

J Androl · 2012 · PMID 22556386 · Publisher ↗

During the fertile window of a woman's menstrual cycle, the effect of impending timed intercourse (TI) on the psychological well-being and behavior of male partners has not been thoroughly investigated, despite the fact... During the fertile window of a woman's menstrual cycle, the effect of impending timed intercourse (TI) on the psychological well-being and behavior of male partners has not been thoroughly investigated, despite the fact that men comprise one half of each couple endeavoring to achieve natural conception. This prospective study consisting of 439 men was conducted during a 3-year period between July 1, 2008, and June 30, 2011. Various characteristics were evaluated, including newly acquired erectile dysfunction (ED); extramarital sex (EMS); intake of soft drinks (SD); levels of hormones, such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), prolactin, and estradiol (E2); and semen parameters. A total of 188 men (42.8%) experienced ED and 47 men (10.7%) engaged in EMS. As the number of TI episodes increased, the number of men with ED and EMS and those who wanted to avoid TI also increased (all, P < .0001). All 47 men who reported EMS experienced ED with their spouses. Men who consumed SDs produced significantly smaller volumes of semen (P = .0363). Among the hormones investigated, the levels of LH, T, and E2 were significantly lower in men with ED (all, P < .05) whereas the level of FSH was higher in contrast to E2, which was significantly higher in men who had EMS (both, P < .01). TI imposes a great deal of stress on male partners evoking ED and, in some cases, causing these men to seek EMS. Physicians and clinicians should acknowledge the potential harmful effects of TI on men. Furthermore, both female and male partners should also be cautioned about the increased possibilities of ED and EMS as TI incidents increase.

Hypoxia-induced deacetylation is required for tetraploid differentiation in response to testicular ischemia-reperfusion (IR) injury.

Hou W, Dong Y, Zhang J … +4 more , Yin Z, Wen H, Xiong L, Li W

J Androl · 2012 · PMID 22556385 · Publisher ↗

Accumulated understanding of epigenetic modifications during ischemia-reperfusion (IR) injury suggests that additional targeted approaches and novel mechanisms that have not been explored in the reproductive system under... Accumulated understanding of epigenetic modifications during ischemia-reperfusion (IR) injury suggests that additional targeted approaches and novel mechanisms that have not been explored in the reproductive system underlie the pathogenesis. Here we show, with a standard murine model of testicular IR, ischemia-induced histone deacetylase (HDAC) activity in the testis with concomitant reduction in histone acetyl transferase activity in vivo. Pretreatment with chemical HDAC inhibitors significantly induced apoptosis in tetraploid pachytene spermatocytes during ischemic insult and thereafter resulted in attenuated meiotic differentiation. We also identified the distinct HDACs involved in primary spermatocytes upon hypoxic stress. In vitro, elevated expression of HDAC2 was physiologically associated with p53, a master regulator believed to be a guardian of genome integrity during spermatogenesis. p53-mediated apoptosis was inhibited by deacetylation of p53 in differentiating pachytene spermatocytes in response to ischemic stress. Overall, the current data suggest that hypoxia-induced deacetylation may operate as an indispensible defensive mechanism for meiotic differentiation during the ischemic period of IR testis, thus pointing to a novel therapeutic target for future medical intervention.

Monthly variation in acute urinary retention incidence among patients with benign prostatic enlargement in Taiwan.

Keller JJ, Lin CC, Chen CS … +2 more , Chen YK, Lin HC

J Androl · 2012 · PMID 22518826 · Publisher ↗

Acute urinary retention (AUR) is characterized by a sudden and painful inability to pass urine and is the most common urological emergency. However, according to our knowledge, no study to date has attempted to explore t... Acute urinary retention (AUR) is characterized by a sudden and painful inability to pass urine and is the most common urological emergency. However, according to our knowledge, no study to date has attempted to explore the monthly variation of AUR after adjusting for climatic parameters. This study aimed to examine the monthly variation of AUR due to benign prostatic enlargement (BPE) in Taiwan. The data used in this study were sourced from 2 datasets: the Longitudinal Health Insurance Database 2005 and a meteorological dataset supplied by the Taiwan Central Weather Bureau. We identified 1406 patients aged 40 years or more with a diagnosis of BPE that could all be followed throughout a 6-year study period (2003-2008). We used the autoregressive integrated moving average (ARIMA) method to examine the incidence of AUR for seasonality. The results show that January (midwinter) had the highest rates, decreasing in March to a trough in June (early summer). The incidence then increased again and reached a peak in December (early winter). The ARIMA test also revealed significant monthly variation in the incidence of AUR. In addition, the ARIMA regression revealed that January, February, August, October, November, and December had significantly higher monthly incidence rates of AUR compared with June, after adjusting for the time trend effect and climatic parameters. Our study concluded that significant monthly variation in the incidence of AUR occurred, and January (midwinter) had the highest rates.

Perspectives and editorials: letter to the editor.

Saliminejad K, Ahani A, Khorshid HR

J Androl · 2012 · PMID 22518825 · Publisher ↗

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A unique patient presenting with concomitant Klinefelter syndrome, Alport syndrome, and craniopharyngioma.

Rotondi M, Fallerini C, Pirali B … +6 more , Longo I, Pasquali D, Rampino T, Chiovato L, Mari F, Renieri A

J Androl · 2012 · PMID 22518824 · Publisher ↗

A 31-year-old Caucasian male was referred for panhypopituitarism resulting from a surgically removed craniopharyngioma. The patient had been previously submitted to kidney transplantation for end-stage renal disease from... A 31-year-old Caucasian male was referred for panhypopituitarism resulting from a surgically removed craniopharyngioma. The patient had been previously submitted to kidney transplantation for end-stage renal disease from X-linked Alport syndrome (ATS). Subsequent quantitative fluorescent polymerase chain reaction analysis indicated a 47,XXY karyotype consistent with Klinefelter syndrome (KS). The relevance of this unique case stems from several issues: 1) KS was an unexpected finding because of a previous diagnosis of hypogonadotropic hypogonadism resulting from craniopharyngioma; 2) the discovery of a de novo p.G406S substitution causing ATS; and 3) the multifactor origin of severe sexual dysfunction. This is the first description of the co-occurrence of KS, ATS, and craniopharyngioma.

Semen quality in males with latent genital infections.

Esipov A

J Androl · 2012 · PMID 22518823 · Publisher ↗

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Luteinizing hormone (LH)-releasing hormone agonist reduces serum adrenal androgen levels in prostate cancer patients: implications for the effect of LH on the adrenal glands.

Nishii M, Nomura M, Sekine Y … +6 more , Koike H, Matsui H, Shibata Y, Ito K, Oyama T, Suzuki K

J Androl · 2012 · PMID 22492843 · Publisher ↗

Recently, adrenal androgens have been targeted as key hormones for the development of castration-resistant prostate cancer therapeutics. Although circulating adrenal androgens originate mainly from the adrenal glands, th... Recently, adrenal androgens have been targeted as key hormones for the development of castration-resistant prostate cancer therapeutics. Although circulating adrenal androgens originate mainly from the adrenal glands, the testes also supply about 10%. Although widely used in androgen deprivation medical castration therapy, the effect of luteinizing hormone-releasing hormone (LH-RH) agonist on adrenal androgens has not been fully studied. In this study, changes in testicular and adrenal androgen levels were measured and compared to adrenocorticotropic hormone levels. To assess the possible role of LH in the adrenal glands, immunohistochemical studies of the LH receptor in normal adrenal glands were performed. Forty-seven patients with localized or locally progressive prostate cancer were treated with LH-RH agonist with radiotherapy. Six months after initiation of treatment, testosterone, dihydrotestosterone, and estradiol levels were decreased by 90%-95%, and dehydroepiandrosterone-sulfate, dehydroepiandrosterone, and androstenedione levels were significantly decreased by 26%-40%. The suppressive effect of LH-RH agonist at 12 months was maintained. Adrenocorticotropic hormone levels showed an increasing trend at 6 months and a significant increase at 12 months. LH receptors were positively stained in the cortex cells of the reticular layer of the adrenal glands. The long-term LH-RH agonist treatment reduced adrenal-originated adrenal androgens. LH receptors in the adrenal cortex cells of the reticular layer might account for the underlying mechanism of reduced adrenal androgens.

The high frequency of sperm aneuploidy in klinefelter patients and in nonobstructive azoospermia is due to meiotic errors in euploid spermatocytes.

Vialard F, Bailly M, Bouazzi H … +7 more , Albert M, Pont JC, Mendes V, Bergere M, Gomes DM, de Mazancourt P, Selva J

J Androl · 2012 · PMID 22492842 · Publisher ↗

For nonobstructive azoospermic (NOA) patients with a normal karyotype or for Klinefelter syndrome (47,XXY) patients, intracytoplasmic sperm injection is associated with an increased aneuploidy risk in offspring. We exami... For nonobstructive azoospermic (NOA) patients with a normal karyotype or for Klinefelter syndrome (47,XXY) patients, intracytoplasmic sperm injection is associated with an increased aneuploidy risk in offspring. We examined testicular cells from patients with different azoospermia etiologies to determine the origin of the aneuploid spermatozoa. The incidence of chromosome abnormalities was investigated in all types of azoospermia. Four study subgroups were constituted: Klinefelter patients (group 1), NOA patients with spermatogenesis failure but a normal karyotype (group 2), obstructive azoospermic patients with normal spermatogenesis (group 3), and control patients with normal sperm (group 4). The pachytene stage (in the three azoospermic groups) and postmeiotic cells (in all groups) were analyzed with fluorescence in situ hybridization. No aneuploid pachytene spermatocytes were observed. Postmeiotic aneuploidy rates were higher in the two groups with spermatogenesis failure (5.3% and 4.0% for groups 1 and 2, respectively) than in patients with normal spermatogenesis (0.6% for group 3 and group 4). Whatever the etiology of the azoospermia, the spermatozoa originated from euploid pachytene spermatocytes. These results strengthen the hypothesis whereby sperm aneuploidy in both Klinefelter patients and NOA patients with a normal karyotype results from meiotic abnormalities and not from aneuploid spermatocytes. The fact that sperm aneuploidy was more frequent when spermatogenesis was altered suggests a deleterious testicular environment. The study results also provide arguments for offering preimplantation genetic diagnosis or prenatal diagnosis when a pregnancy occurs for fathers with NOA (whatever the karyotype).

Low amounts and high thiol oxidation of peroxiredoxins in spermatozoa from infertile men.

Gong S, San Gabriel MC, Zini A … +2 more , Chan P, O'Flaherty C

J Androl · 2012 · PMID 22492841 · Publisher ↗

Seminal oxidative stress occurs when there is an increased production of reactive oxygen species (ROS) and/or a decrease of antioxidant activity, promoting impaired sperm function. Peroxiredoxins (PRDX) are abundant in h... Seminal oxidative stress occurs when there is an increased production of reactive oxygen species (ROS) and/or a decrease of antioxidant activity, promoting impaired sperm function. Peroxiredoxins (PRDX) are abundant in human semen and are important antioxidant enzymes, which act as ROS scavengers and modulators in ROS-dependent signaling. Our aim was to determine whether the levels of PRDX1 and PRDX6 and their oxidation on thiol groups are associated with a decrease in sperm motility and DNA integrity. We evaluated the sperm and seminal PRDX level in men (13 healthy controls, 15 men with clinical varicocele, and 17 men with idiopathic infertility). We assessed conventional semen parameters, sperm DNA integrity (by the sperm chromatin structure assay), lipid peroxidation in seminal plasma and spermatozoa (by the thiobarbituric acid reactive substances assay), and the amount and thiol oxidation of PRDX1 and PRDX6 (by immunoblotting). PRDXs were affected in seminal plasma (lower amounts) and in sperm samples (lower amounts and higher levels of thiol oxidation) characterized by lower sperm motility, higher lipid peroxidation, and sperm DNA damage. The thioloxidation ratio of PRDXs (thiol-oxidized PRDX/total PRDX) correlated negatively with sperm motility (total and progressive) and positively with sperm DNA damage and sperm lipid peroxidation. In conclusion, because of the lower amount of total PRDX1 and PRDX6 and the high thiol oxidation of these PRDXs, very little (less than 20%) protection due to PRDXs remains, and this is associated with impaired sperm function and poor DNA integrity and suggests an important role of PRDXs in the protection of human spermatozoa against oxidative stress.

Chronic oral administration of the arginase inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) improves erectile function in aged rats.

Segal R, Hannan JL, Liu X … +7 more , Kutlu O, Burnett AL, Champion HC, Kim JH, Steppan J, Berkowitz DE, Bivalacqua TJ

J Androl · 2012 · PMID 22492840 · Full text

Arginase expression and activity have been noted to be heightened in conditions associated with erectile dysfunction, including aging. Previously, arginase inhibition by chronic administration of the arginase inhibitor 2... Arginase expression and activity have been noted to be heightened in conditions associated with erectile dysfunction, including aging. Previously, arginase inhibition by chronic administration of the arginase inhibitor 2-(S)-amino-6-boronohexanoic acid (ABH) has been shown to improve endothelial dysfunction in aged rats. The objective of this study was to assess whether chronic oral ABH administration affects cavernosal erectile function. Rats were divided into 4 groups: young control, young treated with arginase inhibitor, aged control, and aged treated with arginase inhibitor. Arginase activity was measured and presented as a proportion of young untreated rats. In vivo erectile responses to cavernous nerve stimulation were measured in all cohorts. The cavernous nerve was stimulated with a graded electrical stimulus, and the intracavernosal/mean arterial pressure ratios and total intracavernosal pressure were recorded. Arginase activity was elevated in the aged rats compared with young controls; however, arginase activity was significantly decreased in aged rats treated with ABH. With the addition of ABH, erectile responses improved in the aged rats (P < .05). Oral inhibition of arginase with ABH results in improved erectile function in aged rats, resulting in erectile hemodynamics similar to young rats. This represents the first documentation of systemic arginase inhibition positively affecting corporal cavernosal function.
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