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  Citation statistics : Table of Contents
   2015| March-April  | Volume 17 | Issue 2  
    Online since February 20, 2015

 
 
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REVIEW
Oxidative phosphorylation versus glycolysis: what fuel do spermatozoa use?
Stefan S du Plessis, Ashok Agarwal, Gayatri Mohanty, Michelle van der Linde
March-April 2015, 17(2):230-235
DOI:10.4103/1008-682X.135123  PMID:25475660
Spermatozoa are highly specialized cells. Adenosine triphosphate (ATP), which provides the energy for supporting the key functions of the spermatozoa, is formed by 2 metabolic pathways, namely glycolysis and oxidative phosphorylation (OXPHOS). It is produced in the mitochondria through OXPHOS as well as in the head and principal piece of the flagellum through glycolysis. However, there is a great discrepancy as to which method of ATP production is primarily utilized by the spermatozoa for successful fertilization. Mitochondrial respiration is considered to be a more efficient metabolic process for ATP synthesis in comparison to glycolysis. However, studies have shown that the diffusion potential of ATP from the mitochondria to the distal end of the flagellum is not sufficient to support sperm motility, suggesting that glycolysis in the tail region is the preferred pathway for energy production. It is suggested by many investigators that although glycolysis forms the major source of ATP along the flagellum, energy required for sperm motility is mainly produced during mitochondrial respiration. Nevertheless, some studies have shown that when glycolysis is inhibited, proper functioning and motility of spermatozoa remains intact although it is unclear whether such motility can be sustained for prolonged periods of time, or is sufficiently vigorous to achieve optimal fertilization. The purpose of this article is to provide an overview of mammalian sperm energy metabolism and identify the preferred metabolic pathway for ATP generation which forms the basis of energy production in human spermatozoa during fertilization.
  67 4,731 862
ORIGINAL ARTICLES
Alterations of gene profiles in Leydig-cell-regenerating adult rat testis after ethane dimethane sulfonate-treatment
Yu-Fei Zhang, Kai-Ming Yuan, Yong Liang, Yan-Hui Chu, Qing-Quan Lian, Yu-Fei Ge, Wei Zhen, Chantal M Sottas, Zhi-Jian Su, Ren-Shan Ge
March-April 2015, 17(2):253-260
DOI:10.4103/1008-682X.136447  PMID:25337835
Only occupying about 1%-5% of total testicular cells, the adult Leydig cell (ALC) is a unique endocrine cell that produces androgens. Rat Leydig cells regenerate after these cells in the testis are eliminated with ethane dimethane sulfonate (EDS). In this study, we have characterized Leydig cell regeneration and messenger ribonucleic acids (mRNA) profiles of EDS treated rat testes. Serum testosterone, testicular gene profiling and some steroidogenesis-related proteins were analyzed at 7, 21, 35 and 90 days after EDS treatment. Testicular testosterone levels declined to undetectable levels until 7 days after treatment and then started to recover. Seven days after treatment, 81 mRNAs were down-regulated greater than or equal to two-fold, with 48 becoming undetectable. These genes increased their expression 21 days and completely returned to normal levels 90 days after treatment. The undetectable genes include steroidogenic pathway proteins: steroidogenic acute regulatory protein, Scarb1, Cyp11a1, Cyp17a1, Hsd3b1, Cyp1b1 and Cyp2a1. Seven days after treatment, there were 89 mRNAs up-regulated two-fold or more including Pkib. These up-regulated mRNAs returned to normal 90 days after treatment. Cyp2a1 did not start to recover until 35 days after treatment, indicating that this gene is only expressed in ALCs not in the precursor cells. Quantitative polymerase chain reaction, western blotting and semi-quantitative immunohistochemical staining using tissue array confirmed the changes of several randomly picked genes and their proteins.
  20 2,733 375
Serum 25-hydroxyvitamin D levels and testosterone deficiency in middle-aged Korean men: a cross-sectional study
Young Jin Tak, Jeong Gyu Lee, Yun Jin Kim, Nam Cheol Park, Sang Soo Kim, Sangyeoup Lee, Byung Mann Cho, Eun Hee Kong, Dong Wook Jung, Yu Hyeon Yi
March-April 2015, 17(2):324-328
DOI:10.4103/1008-682X.142137  PMID:25532570
Previous studies have demonstrated that male hypogonadism is associated with a low level of vitamin D. However, no reports have investigated the effects of vitamin D on testosterone levels in Korean men. Our aim was to investigate whether testosterone levels are associated with serum vitamin D levels and whether seasonal variation exists. This cross-sectional study analyzed serum 25-hydroxyvitamin D [25(OH)D], total testosterone (TT), and free testosterone (FT) in 652 Korean men over 40 years of age who had undergone a comprehensive medical examination. The average age of the subjects was 56.7 ± 7.9 years, and the mean serum 25(OH)D, TT and FT levels were 21.23 ± 7.9 ng ml−1 , 4.70 ± 1.6 ng ml−1 , and 8.12 ± 3.3 pg ml−1 , respectively. In the multiple linear regression model, 25(OH)D showed positive association with TT (β =0.137, P< 0.001) and FT (β =0.103, P= 0.008). 25(OH)D and FT showed similar seasonal or monthly variation after adjustment for age. A vitamin D deficiency [25(OH)D < 20 ng ml−1 ] was associated with an increased risk of deficiencies of TT (<2.30 ng ml−1 ) (odds ratio [OR]: 2.65; 95% confidence interval [CI]: 1.21-5.78, P= 0.014) and FT (<6.50 pg ml−1 ) (OR: 1.44; 95% CI: 1.01-2.06 P= 0.048) after adjusting for age, season, body mass index, body composition, chronic disease, smoking, and alcohol use. In conclusion, we demonstrated a positive correlation between 25(OH)D and testosterone, which showed similar seasonal variation in Korean men.
  16 8,572 537
REVIEW
Controversies in testosterone replacement therapy: testosterone and cardiovascular disease
Kathleen Hwang, Martin Miner
March-April 2015, 17(2):187-191
DOI:10.4103/1008-682X.146968  PMID:25652628
The role of testosterone in the cardiovascular (CV) health of men is controversial. Data suggest that both the condition and treatment of clinical hypogonadism is associated with decreased CV mortality; however, two recent studies suggest that hypogonadal subjects treated with testosterone replacement therapy have a higher incidence of new CV events. There has been increased media attention concerning the risk of CV disease in men treated with testosterone. Until date, there are no long-term prospective studies to determine safety. Literature spanning over the past 30 years has suggested that not only is there a possible increased CV risk in men with low levels of testosterone, but the benefits from testosterone therapy may even lower this risk. We review here the recent studies that have garnered such intense scrutiny. This article is intended as a thorough review of testosterone levels and CV risk, providing the clinician with the facts needed to make informed clinical decisions in managing patients with clinical hypogonadism.
  16 3,854 756
ORIGINAL ARTICLES
Anatase titanium dioxide nanoparticles in mice: evidence for induced structural and functional sperm defects after short-, but not long-, term exposure
Michelle A Smith, Rowan Michael, Rolands G Aravindan, Soma Dash, Syed I Shah, Deni S Galileo, Patricia A Martin-DeLeon
March-April 2015, 17(2):261-268
DOI:10.4103/1008-682X.143247  PMID:25370207
Titanium dioxide (TiO 2 ) nanoparticles (TNPs) are widely used commercially and exist in a variety of products. To determine if anatase TNPs (ATNPs) in doses smaller than previously used reach the scrotum after entry in the body at a distant location and induce sperm defects, 100% ATNP (2.5 or 5 mg kg−1 body weight) was administered intraperitoneally to adult males for three consecutive days, followed by sacrifice 1, 2, 3, or 5 weeks later (long-) or 24, 48 or 120 h (short-term exposure). Transmission electron microscopy revealed the presence of ANTP in scrotal adipose tissues collected 120 h postinjection when cytokine evaluation showed an inflammatory response in epididymal tissues and fluid. At 120 h and up to 3 weeks postinjection, testicular histology revealed enlarged interstitial spaces. Significantly increased numbers of terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling-positive (apoptotic) germ (P = 0.002) and interstitial space cells (P = 0.04) were detected in treated males. Caudal epididymal sperm from the short-term, but not a long-term, arm showed significantly (P < 0.001) increased frequencies of flagellar abnormalities, excess residual cytoplasm (ERC), and unreacted acrosomes in treated versus controls (dose-response relationship). A novel correlation between ERC and unreacted acrosomes was uncovered. At 120 h, there were significant decreases in hyperactivated motility (P < 0.001) and mitochondrial membrane potential (P < 0.05), and increased reactive oxygen species levels (P < 0.00001) in treated versus control sperm. These results indicate that at 4-8 days postinjection, ANTP induce structural and functional sperm defects associated with infertility, and DNA damage via oxidative stress. Sperm defects were transient as they were not detected 10 days to 5 weeks postinjection.
  13 2,297 351
Survey of knowledge, attitude, and practice regarding reproductive health among urban men in China: a descriptive study
Ling Zhang, Rui-Long Gong, Qing-Rong Han, Yu-Qin Shi, Quan-An Jia, Shan-Dan Xu, Le-Qun Wang, Chang-Cai Zhu
March-April 2015, 17(2):309-314
DOI:10.4103/1008-682X.142139  PMID:25532571
There has been little focus on men's reproductive health (RH) in China. This descriptive study conducted in Yiling District, Yichang, China, surveyed male knowledge of sexual physiology and RH to assess levels of knowledge, attitudes and practices (KAPs) regarding prevention of sexually transmitted diseases (STDs). A total of 3933 men, aged 18-59 years (mean, 40.3 years), were recruited by cluster random sampling. They completed a questionnaire in the presence of an interviewer, with items related to subject characteristics, RH knowledge, and subjective symptoms of the reproductive system. Physical examination and reproductive system disease diagnosis were performed. Participants' occupations were predominantly skilled labor (80.5%). Nearly four-fifths (78.5%) respondents had at least one reproductive disease. Over half of respondents were aware of and declared a positive attitude about sexual physiology and safe sex, and 70% of them selected to visit a doctor when they had a reproductive disorder. However, only 41.9% believed human immunodeficiency virus/acquired immunodeficiency syndrome could be transmitted through breastfeeding, and 64.6% incorrectly thought they could avoid contracting STDs by cleaning their genitals after intercourse. In addition, 45% discriminated against and were unwilling to be friends with infected persons. Nearly 45% of those with a reproductive system disorder refused to discuss it with friends or family members. These results indicate that this cohort of Chinese men had a certain degree of KAP about RH, whereas some aspects require further public health education in the general population. It is necessary to disseminate accurate knowledge of STD risk in China based on sociodemographic characteristics.
  12 3,722 415
REVIEW
Testosterone and benign prostatic hyperplasia
Thomas R Jarvis, Bilal Chughtai, Steven A Kaplan
March-April 2015, 17(2):212-216
DOI:10.4103/1008-682X.140966  PMID:25337845
The use of testosterone to treat the symptoms of late-onset hypogonadal men has increased recently due to patient and physician awareness. However, concerns regarding the effect of testosterone on the prostate, in particular any possible effect on the risk of prostate cancer have prompted further research in this regard. Surprisingly, numerous retrospective or small, randomized trials have pointed to a possible improvement in male lower urinary tract symptoms (LUTS) in patients treated with testosterone. The exact mechanism of this improvement is still debated but may have a close relationship to metabolic syndrome. For the clinician, the results of these studies are promising but do not constitute high levels of evidence. A thorough clinical examination (including history, examination and laboratory testing of testosterone) should be undertaken before considering the diagnosis of late-onset hypogonadism or instigating treatment for it. Warnings still remain on the testosterone supplement product labels regarding the risk of urinary retention and worsening LUTS, and these should be explained to patients.
  11 5,481 638
Diagnosis and management of testosterone deficiency
James A McBride, Culley C Carson, Robert M Coward
March-April 2015, 17(2):177-186
DOI:10.4103/1008-682X.143317  PMID:25532575
Testosterone supplementation therapy (TST) use has dramatically increased over the past decade, due to the availability of newer agents, aggressive marketing, and an increasing incidence of testosterone deficiency (TD). Despite the increase in TST, a degree of ambiguity remains as to the exact diagnostic criteria of TD, and administration and monitoring of TST. One explanation for this phenomenon is the complex role testosterone plays in multiple physiologic pathways. Numerous medical co-morbidities and medications can alter testosterone levels resulting in a wide range of nonspecific clinical signs and symptoms of TD. The diagnosis is also challenging due to the lack of a definitive serum total testosterone level that reliably correlates with symptoms. This observation is particularly true in the aging male and is exacerbated by inconsistencies between different laboratory assays. Several prominent medical societies have developed guideline statements to clarify the diagnosis, but they differ from each other and with expert opinion in several ways. Aside from diagnostic dilemmas, there are numerous subtle advantages and disadvantages of the various testosterone agents to appreciate. The available TST agents have changed significantly over the past decade similar to the trends in the diagnosis of TD. Therefore, as the usage of TST increases, clinicians will be challenged to maintain an up-to-date understanding of TD and TST. The purpose of this review is to provide a clear description of the current strategies for diagnosis and management of TD.
  10 4,413 804
ORIGINAL ARTICLES
Late-onset hypogonadism: beyond testosterone
Carlo Foresta, Aldo E Calogero, Francesco Lombardo, Andrea Lenzi, Alberto Ferlin
March-April 2015, 17(2):236-238
DOI:10.4103/1008-682X.135985  PMID:25248651
Late-onset hypogonadism is defined as a combination of low testosterone (T) levels and typical symptoms and signs. A major area of uncertainty is whether T concentrations are always really sufficient to fully reflect Leydig cell (dys)function. Mild testicular alteration could be diagnosed only by additional biochemical markers, such as luteinizing hormone (LH) and 25-hydroxyvitamin D levels. These markers help in identifying the so-called "subclinical" hypogonadism (normal T, high LH levels). Patients with hypogonadism have frequently low levels of 25-hydroxyvitamin D due to impairment of the hydroxylating enzyme CYP2R1 in the testis. However, no data have been published dealing with the best treatment option (cholecalciferol - the Vitamin D precursor, or calcidiol - 25-hydroxylated form of Vitamin D) in these patients. We studied 66 patients with classic hypogonadism (total T [TT] <12 nmol l−1 , LH ≥ 8 IU l−1 ) (n = 26) and subclinical hypogonadism (TT ≥ 12 nmol l−1 , LH ≥ 8 IU l−1 ) (n = 40) and low 25-hydroxyvitamin D (<50 nmol l−1 ). Subjects received cholecalciferol (5000 IU per week) (n = 20) or calcidiol (4000 IU per week) (n = 46), and 25-hydroxyvitamin D and parathyroid hormone (PTH) were evaluated after 3 months of therapy. Supplementation with calcidiol significantly increased 25-hydroxyvitamin D and significantly decreased PTH levels in both groups of men with hypogonadism (primary, n = 16 and subclinical, n = 30), whereas supplementation with cholecalciferol did not modify their levels. This study shows for the first time that the administration of the 25-hydroxylated form of Vitamin D (calcidiol), and not the administration of the precursor cholecalciferol, restores 25-hydroxyvitamin D levels in subjects with hypogonadism.
  9 2,582 634
Validation of robot-assisted vasectomy reversal
Parviz K Kavoussi
March-April 2015, 17(2):245-247
DOI:10.4103/1008-682X.142141  PMID:25475663
Vasectomy reversal (VR) has traditionally been performed with the operative microscope. Recently, robot assistance has been applied to VR. Retrospective chart review from a single VR center included men who underwent either robot-assisted VR (RAVR) or microsurgical VR (MVR) by a single fellowship trained microsurgeon between 2011 and 2013 and had a 6 weeks postoperative semen analysis. Fifty-two men who were interested in VR were counseled and given the option of RAVR versus MVR. Twenty-seven men elected to have MVR while 25 men elected RAVR. These included vasovasostomies and vasoepididymostomies in both groups, as well as redo VRs in men who had failed previous VR attempts by other surgeons. There was no statistically significant difference between the microsurgical group and the robot-assisted group, respectively, in overall patency rates (89% vs 92%), 6 weeks post-VR mean sperm concentrations (28 million ml−1 vs 26 million ml−1 ) or total motile counts (29 million vs 30 million), or mean operative times (141 min vs 150 min). There was a statistically significant difference in anastomosis time (64 min vs 74 min), however, clinically this only represented a 10 min longer anastomosis time in the early robotic experience, which was found to be decreasing as the case series continued. Transitioning from MVR to RAVR is feasible with comparable outcomes.
  9 1,951 303
Follicle-stimulating hormone as a predictor for sperm retrieval rate in patients with nonobstructive azoospermia: a systematic review and meta-analysis
Qi Yang, Yan-Ping Huang, Hong-Xiang Wang, Kai Hu, Yi-Xin Wang, Yi-Ran Huang, Bin Chen
March-April 2015, 17(2):281-284
DOI:10.4103/1008-682X.139259  PMID:25337843
Noninvasive parameters for predicating sperm retrieval rate (SRR) are desirables. Follicle-stimulating hormone (FSH) has been an important predictor since the first years of testicular sperm extraction. Recent studies showed continuous interests in FSH, with both pros and cons. Thus, we conducted a meta-analysis to evaluate the diagnostic value of FSH as a predictor for patients with nonobstructive azoospermia (NOA) taking testicular sperm retrieval. Eligible diagnosis tests were identified from electronic databases (Cochrane Central Register of Controlled Trials, Medline, and EMBASE) without language restrictions. The database search, quality assessment, and data extraction were performed independently by two reviewers. The reference standard was the sperm retrieval result. Diagnostic value of FSH were explored by area under receiver operation characteristics (ROC) curve using Review Manager, version 5.1.0 (Cochrane Collaboration, Oxford, UK) and Meta-DiSc, version 1.4. Meta regression will be done if there is heterogeneity. Then, we find 11 tests including a total of 1350 patients met the inclusion criteria. Our pooled analysis showed that the area under ROC curve of FSH was 0.72 ± 0.04. Meta regression analyses showed that region and average age have an influence on the diagnostic value. FSH showed more diagnostic value with patients in East Asia and with younger patients. We concluded that FSH had moderate value in independently predicating SRR in men with NOA (area under curve >0.7). More detailed diagnosis tests should be anticipated in the future to confirm the diagnostic value of other noninvasive parameters.
  9 2,539 426
REVIEW
Preserving fertility in the hypogonadal patient: an update
Ranjith Ramasamy, Joseph M Armstrong, Larry I Lipshultz
March-April 2015, 17(2):197-200
DOI:10.4103/1008-682X.142772  PMID:25337850
An increasing number of young and middle-aged men are seeking treatment for symptoms related to deficient levels of androgens (hypogonadism) including depression, loss of libido, erectile dysfunction, and fatigue. The increase in prevalence of testosterone supplementation in general and anabolic steroid-induced hypogonadism specifically among younger athletes is creating a population of young men who are uniquely impacted by the testicular end-organ negative consequences of exogenous steroid use. Exogenous testosterone therapy can alter the natural regulation of the hypothalamic-pituitary-gonadal axis leading to impaired spermatogenesis with azoospermia being a serious possible result, thus rendering the individual infertile. For men of reproductive age who suffer from hypogonadal symptoms, preservation of fertility is an important aspect of their treatment paradigm. Treatment with human chorionic gonadotropin (hCG) has shown the ability not only to reverse azoospermia brought on by testosterone supplementation therapy but also to help maintain elevated intratesticular testosterone levels. In addition, selective estrogen receptor modulators, often used with hCG have been shown both to elevate total testosterone levels and to maintain spermatogenesis in hypogonadal men.
  9 4,956 712
EDITORIAL
Controversies in testosterone supplementation therapy
Mohit Khera
March-April 2015, 17(2):175-176
DOI:10.4103/1008-682X.148728  PMID:25652639
Testosterone has now become one of the most widely used medications throughout the world. The rapid growth of the testosterone market in the past 10 years is due to many factors. We currently have a worldwide aging population. In the US, the number of men 65 years old or older is increasing 2-3 times faster than the number of men younger than 65 years. In addition, poor general health and certain medical conditions such as diabetes/metabolic syndrome (MetS), cardiovascular disease (CVD), and osteoporosis have been associated with low serum testosterone levels. [1],[2],[3] There are now fewer concerns regarding the development of prostate cancer (PCa) after testosterone therapy, making it a more attractive treatment option. Finally, the introduction of different forms of testosterone supplementation therapy (TST) with increased promotion, marketing, and direct-to-consumer advertising is also driving market growth. As the demand for TST continues to grow, it is becoming more important for clinicians to understand how to diagnose and treat patients with low testosterone.
  8 2,802 713
ORIGINAL ARTICLES
Glycoprotein fucosylation is increased in seminal plasma of subfertile men
Beata Olejnik, Ewa M Kratz, Mariusz Zimmer, Mirosława Ferens-Sieczkowska
March-April 2015, 17(2):274-280
DOI:10.4103/1008-682X.138187  PMID:25248658
Fucose, the monosaccharide frequent in N- and O-glycans, is a part of Lewis-type antigens that are known to mediate direct sperm binding to the zona pellucida. Such interaction was found to be inhibited in vitroby fucose-containing oligo- and polysaccharides, as well as neoglycoproteins. The objective of this study was to screen seminal plasma proteins of infertile/subfertile men for the content and density of fucosylated glycoepitopes, and compare them to samples of fertile normozoospermic subjects. Seminal proteins were separated in polyacrylamide gel electrophoresis and blotted onto nitrocellulose membrane and probed with fucose-specific Aleuria aurantia lectin (AAL). Twelve electrophoretic bands were selected for quantitative densitometric analysis. It was found that the content, and especially the density of fucosylated glycans, were higher in glycoproteins present in seminal plasma of subfertile men. No profound differences in fucosylation density were found among the groups of normozoospermic, oligozoospermic, asthenozoospermic, and oligoasthenozoospermic subfertile men. According to the antibody probing, AAL-reactive bands can be attributed to male reproductive tract glycoproteins, including prostate-specific antigen, prostatic acid phosphatase, glycodelin and chorionic gonadotropin. Fibronectin, α1 -acid glycoprotein, α1 -antitrypsin, immunoglobulin G and antithrombin III may also contribute to this high fucosylation. It is suggested that the abundant fucosylated glycans in the sperm environment could interfere with the sperm surface and disturb the normal course of the fertilization cascade.
  8 2,398 382
REVIEW
Testosterone and metabolic syndrome
Glenn R Cunningham
March-April 2015, 17(2):192-196
DOI:10.4103/1008-682X.148068  PMID:25652634
Controversies surround the usefulness of identifying patients with the metabolic syndrome (MetS). Many of the components are accepted risk factors for cardiovascular disease (CVD). Although the MetS as defined includes many men with insulin resistance, insulin resistance is not universal. The low total testosterone (TT) and sex hormone binding globulin (SHBG) levels in these men are best explained by the hyperinsulinism and increased inflammatory cytokines that accompany obesity and increased waist circumference. It is informative that low SHBG levels predict future development of the MetS. Evidence is strong relating low TT levels to CVD in men with and without the MetS; however, the relationship may not be causal. The recommendations of the International Diabetes Federation for managing the MetS include cardiovascular risk assessment, lifestyle changes in diet, exercise, weight reduction and treatment of individual components of the MetS. Unfortunately, it is uncommon to see patients with the MetS lose and maintain a 10% weight loss. Recent reports showing testosterone treatment induced dramatic changes in weight, waist circumference, insulin sensitivity, hemoglobin A1c levels and improvements in each of the components of the MetS are intriguing. While some observational studies have reported that testosterone replacement therapy increases cardiovascular events, the Food and Drug Administration in the United States has reviewed these reports and found them to be seriously flawed. Large, randomized, placebo-controlled trials are needed to provide more definitive data regarding the efficacy and safety of this treatment in middle and older men with the MetS and low TT levels.
  8 5,038 863
Alternatives to testosterone replacement: testosterone restoration
Andrew McCullough
March-April 2015, 17(2):201-205
DOI:10.4103/1008-682X.143736  PMID:25578932
The European Male Aging Study has demonstrated that the hypogonadism of male aging is predominantly secondary. Theoretically with appropriate stimulation from the pituitary, the aging testis should be able to produce eugonadal levels of testosterone. The strategies for the treatment of late onset hypogonadism (LOH) have focused on replacement with exogenous testosterone versus restoration of endogenous production. The purpose of this article is to review existing peer-reviewed literature supporting the concept of restoration of endogenous testosterone in the treatment of LOH.
  8 14,699 994
ORIGINAL ARTICLES
Urokinase-type plasminogen activator: a new target for male contraception?
Ying Qin, Yan Han, Cheng-Liang Xiong, Hong-Gang Li, Lian Hu, Ling Zhang
March-April 2015, 17(2):269-273
DOI:10.4103/1008-682X.143316  PMID:25578931
Urokinase-type plasminogen activator (uPA) is closely related to male reproduction. With the aim of investigating the possibility for uPA as a potential contraceptive target, in the present work, Kunming male mice were immunized by human uPA subcutaneous injection at three separate doses for 3 times. Then the potency of the anti-human uPA antibody in serum was analyzed, and mouse fertility was evaluated. Serum antibody titers for human uPA in immunized groups all reached 1:10,240 or higher levels by enzyme linked immunosorbent assay, and mating experiments revealed that pregnancy rates and the mean number of embryos implanted after mating declined obviously (P < 0.05) when compared with control groups. However, the mating capacity and reproductive organ weights had no obvious change, and histological analysis of the testes and epididymides also showed normal morphology for immunized male mice. Sperm function tests suggested that the sperm concentration, sperm viability, sperm motility, and in vitro fertilization rate for the cauda epididymis sperm in uPA-immunized groups were lower than those in the controls (P < 0.05). Together, these observations indicated that subcutaneous injection human uPA to the male mice could effectively reduce their fertility, and uPA could become a new target for immunocontraception in male contraceptive development.
  7 1,681 284
Association between cytochrome CYP17A1, CYP3A4, and CYP3A43 polymorphisms and prostate cancer risk and aggressiveness in a Korean study population
Jun Hyun Han, Yong Seong Lee, Hae Jong Kim, Shin Young Lee, Soon Chul Myung
March-April 2015, 17(2):285-291
DOI:10.4103/1008-682X.133320  PMID:25337833
In this study, we evaluated genetic variants of the androgen metabolism genes CYP17A1, CYP3A4, and CYP3A43 to determine whether they play a role in the development of prostate cancer (PCa) in Korean men. The study population included 240 pathologically diagnosed cases of PCa and 223 age-matched controls. Among the 789 single-nucleotide polymorphism (SNP) database variants detected, 129 were reported in two Asian groups (Han Chinese and Japanese) in the HapMap database. Only 21 polymorphisms of CYP17A1, CYP3A4, and CYP3A43 were selected based on linkage disequilibrium in Asians (r2 = 1), locations (SNPs in exons were preferred), and amino acid changes and were assessed. In addition, we performed haplotype analysis for the 21 SNPs in CYP17A1, CYP3A4, and CYP3A43 genes. To determine the association between genotype and haplotype distributions of patients and controls, logistic analyses were carried out, controlling for age. Twelve sequence variants and five major haplotypes were identified in CYP17A1. Five sequence variants and two major haplotypes were identified in CYP3A4. Four sequence variants and four major haplotypes were observed in CYP3A43. CYP17A1 haplotype-2 (Ht-2) (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.18) was associated with PCa susceptibility. CYP3A4 Ht-2 (OR: 1.87; 95% CI: 1.02-3.43) was associated with PCa metastatic potential according to tumor stage. rs17115149 (OR: 1.96; 95% CI: 1.04-3.68) and CYP17A1 Ht-4 (OR: 2.01; 95% CI: 1.07-4.11) showed a significant association with histologic aggressiveness according to Gleason score. Genetic variants of CYP17A1 and CYP3A4 may play a role in the development of PCa in Korean men.
  6 2,175 391
The reference values for semen parameters of 1213 fertile men in Guangdong Province in China
Yun-Ge Tang, Li-Xin Tang, Qi-Ling Wang, Ge Song, Yan-Jia Jiang, Shun-Mei Deng, Fang Jiang, Wei-Bing Qin
March-April 2015, 17(2):298-303
DOI:10.4103/1008-682X.143251  PMID:25432502
Semen samples were collected from 1213 fertile men whose partners had a time-to-pregnancy (TTP) ≤12 months in Guangdong Province in Southern China, and semen parameters including semen volume, sperm concentration, total counts, motility, and morphology were evaluated according to the World Health Organization (WHO) 2010 guideline. All semen parameters analyzed were normal in ~62.2% of the total samples, whereas ~37.8% showed at least one of the semen parameters below normal threshold values. The fifth centiles (with 95% confidence intervals) were 1.3 (1.2-1.5) ml for semen volume, 20 × 10 6 (18×10 6 -20×10 6 ) ml−1 for sperm concentration, 40 × 10 6 (38×10 6 -44×10 6 ) per ejaculate for total sperm counts, 48% (47%-53%) for vitality, 39% (36%-43%) for total motility, 25% (23%-27%) for sperm progressive motility, 5.0% (4%-5%) for normal morphology. The pH values ranged from 7.2 to 8.0 with the mean ± standard deviation at 7.32 ± 0.17. No effects of age and body mass index were found on semen parameters. Occupation, smoking and alcohol abuse, varicocele appeared to decrease semen quality. Sperm concentration, but not sperm morphology, is positively correlated with TTP, whereas vitality is negatively correlated with TTP. Our study provides the latest reference values for the semen parameters of Chinese fertile men in Guangdong Province, which are close to those described in the new WHO guidelines (5 th Edition).
  6 2,667 443
Randomized clinical trial of a bladder neck plication stitch during robot-assisted radical prostatectomy
Seung-Kwon Choi, Sejun Park, Hanjong Ahn
March-April 2015, 17(2):304-308
DOI:10.4103/1008-682X.139258  PMID:25432493
Urinary incontinence after robot-assisted radical prostatectomy (RARP) is one of the most bothersome complications affecting patients' daily lives. The efficacy of the bladder neck plication stitch technique in promoting an earlier return of continence was prospectively evaluated in 158 patients who underwent RARP for clinically localized prostate cancer by a single surgeon at our institute from March 2012 to January 2013. Patients were randomized 1:1 to undergo surgery with (n = 79) or without (n = 79) the bladder neck plication stitch, and their time to recovery from incontinence, defined as being pad free, was compared. Recovery from incontinence at 1, 3, and 6 months were observed in 22 (27.8%), 42 (53.2%), and 57 (72.2%) patients, respectively, treated with, and 23 (29.1%), 47 (59.5%), and 59 (74.7%) patients, respectively, treated without the bladder neck plication stitch, with no significant difference in time to recovery from incontinence between the two groups. Multivariate analysis showed that age, membranous urethral length and shape of the prostatic apex on magnetic resonance imaging were independent predictors of early recovery from urinary incontinence after RARP. The bladder neck plication stitch had no effect on time to recovery from postoperative urinary incontinence following RARP.
  6 1,683 340
REVIEW
Testosterone therapy in men with prostate cancer: literature review, clinical experience, and recommendations
Abraham Morgentaler, William P Conners
March-April 2015, 17(2):206-211
DOI:10.4103/1008-682X.148067  PMID:25652633
For several decades any diagnosis of prostate cancer (PCa) has been considered an absolute contraindication to the use of testosterone (T) therapy in men. Yet this prohibition against T therapy has undergone recent re-examination with refinement of our understanding of the biology of androgens and PCa, and increased appreciation of the benefits of T therapy. A reassuringly low rate of negative outcomes has been reported with T therapy after radical prostatectomy (RP), radiation treatments, and in men on active surveillance. Although the number of these published reports are few and the total number of treated men is low, these experiences do provide a basis for consideration of T therapy in selected men with PCa. For clinicians considering offering this treatment, we recommend first selecting patients with low grade cancers and undetectable prostate-specific antigen following RP. Further research is required to define the safety of T therapy in men with PCa. However, many patients symptomatic from T deficiency are willing to accept the potential risk of PCa progression or recurrence in return for the opportunity to live a fuller and happier life with T therapy.
  6 4,150 666
ORIGINAL ARTICLES
Serum lipid profiles: novel biomarkers predicting advanced prostate cancer in patients receiving radical prostatectomy
Gui-Ming Zhang, Xiao-Jian Qin, Hai-Liang Zhang, Wen-Jun Xiao, Yao Zhu, Cheng-Yuan Gu, Bo Dai, Guo-Hai Shi, Ding-Wei Ye
March-April 2015, 17(2):239-244
DOI:10.4103/1008-682X.142135  PMID:25475662
This study aimed to evaluate the role of serum lipid profiles as novel biomarkers in predicting pathological characteristics of prostate cancer (PCa). We retrospectively analyzed 322 consecutive patients with clinically localized PCa receiving radical prostatectomy (RP) and extended pelvic lymphadenectomy. Unconditional logistic regression was used to estimate the prostatectomy Gleason score (pGS), pathological stage and lymph node involvement (LNI) in RP specimens. Preoperative prostate-specific antigen (PSA) levels, biopsy GS (bGS), and preoperative tumor, node, metastasis staging were used as basic variables to predict postoperative pathological characteristics. Preoperative serum lipid profiles were introduced as potential predictors. A receiver operating characteristic (ROC) curve was used to determine predictive efficacy. Significant differences in pathological characteristics were observed among patients with normal and abnormal total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels, with the exception of pGS in the TG group. Multivariable regression analysis revealed that the odds ratio for high levels of TC for LNI compared with normal TC levels was 6.386 (95% confidence interval [CI] 1.510-27.010), 3.270 (95% CI: 1.470-7.278) for high levels of TG for pT3-4 disease, and 2.670 (95% CI: 1.134-6.287) for high levels of LDL for pGS. The area under the ROC curve of the models with dyslipidemia was larger than that in models without dyslipidemia, in predicting pathological characteristics. Abnormal TC, TG, and LDL levels are significantly associated with postoperative pathological status in PCa patients. Together with preoperative PSA levels, bGS, and clinical stage, dyslipidemia is more accurate in predicting pathological characteristics.
  5 2,121 356
The relationship between erectile function and complex panurethral stricture: a preliminary investigative and descriptive study
Hong Xie, Yue-Min Xu, Qiang Fu, Ying-Long Sa, Yong Qiao
March-April 2015, 17(2):315-318
DOI:10.4103/1008-682X.143312  PMID:25532574
The aim of this study was to evaluate erectile function in patients with panurethral stricture after urethral reconstruction. Totally, 65 patients were enrolled. Different urethral reconstructions were performed according to the details of urethral strictures. The erectile function was evaluated before and after surgery. The length and location of stricture and duration from initial diagnosis to operation were recorded. The International Index of Erectile Function-5 (IIEF-5) scores, the quality of life (QoL) scores and the maximal flow rate were obtained before and 3, 6, and 12 months after surgery. A significant improvement in QoL and maximal flow rate was observed 3, 6, and 12 months after surgery compared with those observed before surgery (P < 0.05). An impairment of erectile function was observed in patients with multi-site stricture 3 months after surgery (P < 0.05). Subsequently, these patients recovered 6 and 12 months after surgery. Three months after surgery, the IIEF-5 scores in patients with anterior urethral stricture were higher than those with multi-site stricture. Similar results were observed 6 and 12 months after surgery. No significant difference in age or duration from initial diagnosis to final operation was observed between patients with erectile dysfunction after surgery and patients with normal erectile function. However, a linear regressive relationship was detected between IIEF-5 scores and location of urethral stricture. Surgical reconstruction for treating panurethral strictures has limited effects on erectile function. The location of the stricture, particularly when extended to posterior urethra, was found to be associated with erectile function after surgery.
  4 2,286 293
The secretory products of Trichomonas vaginalis decrease fertilizing capacity of mice sperm in vitro
Jaesook Roh, Young-Su Lim, Min-Young Seo, Yuri Choi, Jae-Sook Ryu
March-April 2015, 17(2):319-323
DOI:10.4103/1008-682X.145070  PMID:25578937
Trichomonas vaginalis infection is one of the most prevalent sexually transmitted infections in humans and is now recognized as an important cause of infertility in men. There is little information about the effect of extracellular polymeric substances (EPS) from T. vaginalis on sperm, but previous reports do not provide a conclusive description of the functional integrity of the sperm. To investigate the impact of EPS on the fertilizing capacity of sperm, we assessed sperm motility, acrosomal status, hypo-osmotic swelling, and in vitrofertilization rate after incubating the sperm with EPS in vitrousing mice. The incubation of sperm with EPS significantly decreased sperm motility, viability, and functional integrity in a concentration and time-dependent manner. These effects on sperm quality also resulted in a decreased fertilization rate in vitro. This is the first report that demonstrates the direct negative impact of the EPS of T. vaginalis on the fertilization rate of sperm in vitro. However, further study should be performed using human sperm to determine if EPS has similar negative impact on human sperm fertilizing capacity in vitro.
  4 2,208 326
An epididymis-specific carboxyl esterase CES5A is required for sperm capacitation and male fertility in the rat
Yan-Fei Ru, Hai-Min Xue, Zi-Mei Ni, Dong Xia, Yu-Chuan Zhou, Yong-Lian Zhang
March-April 2015, 17(2):292-297
DOI:10.4103/1008-682X.143314  PMID:25475668
Despite the fact that the phenomenon of capacitation was discovered over half century ago and much progress has been made in identifying sperm events involved in capacitation, few specific molecules of epididymal origin have been identified as being directly involved in this process in vivo . Previously, our group cloned and characterized a carboxyl esterase gene Ces5a in the rat epididymis. The CES5A protein is mainly expressed in the corpus and cauda epididymidis and secreted into the corresponding lumens. Here, we report the function of CES5A in sperm maturation. By local injection of Lentivirus -mediated siRNA in the CES5A -expressing region of the rat epididymis, Ces5a -knockdown animal models were created. These animals exhibited an inhibited sperm capacitation and a reduction in male fertility. These results suggest that CES5A plays an important role in sperm maturation and male fertility.
  4 2,119 366
COMMENTARY
Serum lipid profiles and aggressive prostate cancer
Yanjing Li, Chaozhao Liang, Jiaoti Huang
March-April 2015, 17(2):336-336
DOI:10.4103/1008-682X.143308  PMID:25475667
  3 1,472 281
EXPERIENCE AND HISTORY
Early history of inflatable penile prosthesis surgery: a view from someone who was there
David F Mobley
March-April 2015, 17(2):225-229
DOI:10.4103/1008-682X.140962  PMID:25432494
The publication of the use of an inflatable penile prosthesis (IPP) in 1973 by Dr. FB Scott. changed the world of treatment options for erectile dysfunction (ED). Much has been written since then about techniques, improvements, management of difficult cases, complications and their management, and mechanical and device changes over time. Few reports, if any, are available in the medical literature regarding the early development, surgical techniques, and controversies surrounding its introduction to the world's urological community. This article is, for the most part, the observations of one who was "there" in the early and mid-1970's and was a witness to the history of this remarkable marvel of creativity, engineering, design, and to the personalities involved.
  3 3,240 325
CLINICIANS WORKSHOP
Modified technique in treating recurrent priapism: a technique report
Wei Chen, Shu-Ben Sun, Li-An Sun, Jian-Ming Guo, Guo-Min Wang
March-April 2015, 17(2):329-331
DOI:10.4103/1008-682X.144944  PMID:25578936
Recurrent ischemic priapism is a problem in clinical treatment. Most of the cases require more invasive surgery to shunt the blood stasis. We introduce a modified technique in treating recurrent ischemic priapism. The technique described is applied to acute ischaemic priapic episodes in patients with a history of stuttering priapism. It was carried out by a Winter's shunt combined with a continuous cavernosal irrigation system. Priapism was effectively resolved on the patients without recurrence. The four patients who received this treatment recovered most sexual function after 6 months follow-up.
  2 1,992 369
LETTERS TO THE EDITOR
An idiopathic hypogonadotropic hypogonadism patient with metabolic disorder and diabetes: case report
Man-Na Zhang, Bin Su, Chun-Hua Qian, Le Bu, Xiao-Yun Cheng, Wen-Jun Li, Shen Qu
March-April 2015, 17(2):341-342
DOI:10.4103/1008-682X.137885  PMID:25337838
  2 1,538 322
ORIGINAL ARTICLES
Analysis of expanded criteria to select candidates for active surveillance of low-risk prostate cancer
Jung Ki Jo, Han Sol Lee, Young Ik Lee, Sang Eun Lee, Sung Kyu Hong
March-April 2015, 17(2):248-252
DOI:10.4103/1008-682X.142136  PMID:25432498
We aimed to analyze the value of each criterion for clinically insignificant prostate cancer (PCa) in the selection of men for active surveillance (AS) of low-risk PCa. We identified 532 men who were treated with radical prostatectomy from 2006 to 2013 who met 4 or all 5 of the criteria for clinically insignificant PCa (clinical stage ≤ T1, prostate specific antigen [PSA] density ≤ 0.15, biopsy Gleason score ≤ 6, number of positive biopsy cores ≤ 2, and no core with > 50% involvement) and analyzed their pathologic and biochemical outcomes. Patients who met all 5 criteria for clinically insignificant PCa were designated as group A (n = 172), and those who met 4 of 5 criteria were designated as group B (n = 360). The association of each criterion with adverse pathologic features was assessed via logistic regression analyses. Comparison of group A and B and also logistic regression analyses showed that PSA density > 0.15 ng ml−1 and high (≥7) biopsy Gleason score were associated with adverse pathologic features. Higher (> T1c) clinical stage was not associated with any adverse pathologic features. Although ≤ 3 positive cores were not associated with any adverse pathology, ≥4 positive cores were associated with higher risk of extracapsular extension. Among potential candidates for AS, PSA density > 0.15 ng ml−1 and biopsy Gleason score > 6 pose significantly higher risks of harboring more aggressive disease. The eligibility criteria for AS may be expanded to include men with clinical stage T2 tumor and 3 positive cores.
  2 1,596 262
RESEARCH HIGHLIGHT
What is the next generation therapeutic strategy for castration-resistant prostate cancer
Si-Meng Wen, Chang-Yi Quan, Ning Jiang, Zhi-Qun Shang, Yuan-Jie Niu
March-April 2015, 17(2):223-224
DOI:10.4103/1008-682X.143311  PMID:25432503
Prostate cancer (PCa) is one of the most common cancers in the world. Since androgen receptor (AR) signal plays key roles in the PCa progression, targeting androgens via the current androgen deprivation therapy (ADT) is the main therapeutic strategy for advanced PCa. However, most patients who receive ADT, including the second generation anti-androgens enzalutamide (also known as MDV3100) may finally develop the castration (or anti-androgen) resistance after 12-24 months treatment. In the manuscript by Asangani et al., the authors demonstrated that targeting the amino-terminal bromodomains of BRD4 could preferentially suppress human castration-resistant prostate cancer (CRPC) cell lines. While further studies are required to understand the full impact of their findings, the innovative approach provides a potential novel epigenetic approach for the concerted blockade of oncogenic drivers in CRPC.
  2 2,126 388
COMMENTARY
Commentary on "Late-onset hypogonadism - beyond testosterone"
Geoffrey Hackett
March-April 2015, 17(2):334-334
DOI:10.4103/1008-682X.137679  PMID:25248653
  1 1,708 354
LETTERS TO THE EDITOR
Trends in the placement of penile prostheses over the last 17 years in France
Priscilla Leon, Thomas Seisen, Pierre Mozer, Sébastien Beley, Morgan Rouprêt
March-April 2015, 17(2):337-338
DOI:10.4103/1008-682X.139260  PMID:25248660
  1 1,035 167
RESEARCH HIGHLIGHT
Effect of testosterone replacement treatment on constitutional and sexual symptoms in type 2 diabetic men: need for rules
Fotios Dimitriadis, Nikolaos Sofikitis
March-April 2015, 17(2):217-218
DOI:10.4103/1008-682X.140967  PMID:25432496
In a recent publication, Gianatti and colleagues investigated the effect of testosterone treatment in obese, aging men with type 2 diabetes (T2D) with mild to moderate symptoms, a modest reduction in testosterone levels, mild to moderate aging male symptoms, and erectile dysfunction. [1] The authors could not show any significant improvement in constitutional or sexual symptoms in this group of men. This randomized double-blind, parallel, and placebo-controlled trial among other critically emphasizes the increased testosterone prescriptions worldwide and together with other corroborating or contradictory studies awakes the need for guidelines in the androgen replacement treatment.
  1 1,817 351
COMMENTARY
Extended lymph node dissection for intermediate and high-risk prostate cancer: do we have all the evidence?
Ahmed Ghazi
March-April 2015, 17(2):335-335
DOI:10.4103/1008-682X.143042  PMID:25532572
  - 1,292 237
Commentary on "validation of robot-assisted vasectomy reversal"
Premsant Sangkum, Faysal A Yafi, Wayne JG Hellstrom
March-April 2015, 17(2):332-332
DOI:10.4103/1008-682X.145632  PMID:25578941
  - 1,329 221
Commentary on "validation of robot-assisted vasectomy reversal" by Dr. Parviz K Kavoussi
Sijo J Parekattil
March-April 2015, 17(2):333-333
DOI:10.4103/1008-682X.145631  PMID:25578940
  - 1,180 184
LETTERS TO THE EDITOR
Unusual presentation of urachal adenocarcinoma with genitourinary cutaneous metastasis
Yin-Hui Yang, Yan Zhu, Xiang-Wei Zhu, Hong-Juan Tang, Jian-Guo Hou, Wan-Hai Xu
March-April 2015, 17(2):339-340
DOI:10.4103/1008-682X.139257  PMID:25337842
  - 1,444 254
Clinical features in a man with primary synovial sarcoma of the spermatic cord
Gong-Cheng Wang, Xue-Qin Li, Yun-Yan Wang, Zhong-Ying Guo, Pei-Jin Hou
March-April 2015, 17(2):343-344
DOI:10.4103/1008-682X.143307  PMID:25475666
  - 1,296 215
RESEARCH HIGHLIGHT
Reduced fetal androgen exposure compromises Leydig cell function in adulthood
Katja J Teerds, Jaap Keijer
March-April 2015, 17(2):219-220
DOI:10.4103/1008-682X.143249  PMID:25412675
Disruption of normal fetal development can influence functioning of organs and cells in adulthood. Circumstantial evidence suggests that subtle reductions in fetal androgen production may be the cause of adult male reproductive disorders due to reduced testosterone production. The mechanisms through which these fetal events affect adult testosterone levels are largely unknown. A recent paper of Kilcoyne et al. provides evidence that fetal reduction in androgen production or signaling results in a reduced Leydig stems cell number after birth and concomitant Leydig cell failure in adulthood. This implies that fetal androgen deficiency can lead to negative programming of adult Leydig cell (ALC) function, which may have implications for general health, aging, and longevity.
  - 1,772 304
Appraising the European randomized study of screening for prostate cancer: what do the results mean?
Dragan Ilic
March-April 2015, 17(2):221-222
DOI:10.4103/1008-682X.142131  PMID:25432497
The value of screening for prostate cancer has been a contentious issue within the medical literature for several decades. At the crux of the matter lies a judgment call of whether the potential benefits of screening, a reduction in prostate cancer and all-cause mortality, outweigh the limitations, overdiagnosis and overtreatment. The study by Schrφder et al. reports 9, 11 and 13-year follow-up data on men participating in the European randomized study of screening for prostate cancer (ERSPC). While the authors report a significant reduction in prostate cancer mortality, they conclude that potential harms associated with screening currently circumvent any recommendation for a population-based approach to screening for prostate cancer.
  - 1,390 283
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