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   2016| May-June  | Volume 18 | Issue 3  
    Online since April 18, 2016

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The role of estradiol in male reproductive function
Michael Schulster, Aaron M Bernie, Ranjith Ramasamy
May-June 2016, 18(3):435-440
DOI:10.4103/1008-682X.173932  PMID:26908066
Traditionally, testosterone and estrogen have been considered to be male and female sex hormones, respectively. However, estradiol, the predominant form of estrogen, also plays a critical role in male sexual function. Estradiol in men is essential for modulating libido, erectile function, and spermatogenesis. Estrogen receptors, as well as aromatase, the enzyme that converts testosterone to estrogen, are abundant in brain, penis, and testis, organs important for sexual function. In the brain, estradiol synthesis is increased in areas related to sexual arousal. In addition, in the penis, estrogen receptors are found throughout the corpus cavernosum with high concentration around neurovascular bundles. Low testosterone and elevated estrogen increase the incidence of erectile dysfunction independently of one another. In the testes, spermatogenesis is modulated at every level by estrogen, starting with the hypothalamus-pituitary-gonadal axis, followed by the Leydig, Sertoli, and germ cells, and finishing with the ductal epithelium, epididymis, and mature sperm. Regulation of testicular cells by estradiol shows both an inhibitory and a stimulatory influence, indicating an intricate symphony of dose-dependent and temporally sensitive modulation. Our goal in this review is to elucidate the overall contribution of estradiol to male sexual function by looking at the hormone's effects on erectile function, spermatogenesis, and libido.
  11,084 1,451 80
Male infertility: lifestyle factors and holistic, complementary, and alternative therapies
David F Yao, Jesse N Mills
May-June 2016, 18(3):410-418
DOI:10.4103/1008-682X.175779  PMID:26952957
While we may be comfortable with an allopathic approach to male infertility, we are also responsible for knowledge about lifestyle modifications and holistic, complementary, and alternative therapies that are used by many of our patients. This paper provides an evidence-based review separating fact from fiction for several of these therapies. There is sufficient literature to support weight reduction by diet and exercise, smoking cessation, and alcohol moderation. Supplements that have demonstrated positive effects on male fertility on small randomized controlled trial (RCT) include aescin, coenzyme Q 10 , glutathione, Korean red ginseng, L-carnitine, nigella sativa, omega-3, selenium, a combination of zinc and folate, and the Menevit antioxidant. There is no support for the use of Vitamin C, Vitamin E, or saffron. The data for Chinese herbal medications, acupuncture, mind-body practice, scrotal cooling, and faith-based healing are sparse or inconclusive.
  9,731 1,436 20
Recovery of spermatogenesis following testosterone replacement therapy or anabolic-androgenic steroid use
J Abram McBride, Robert M Coward
May-June 2016, 18(3):373-380
DOI:10.4103/1008-682X.173938  PMID:26908067
The use of testosterone replacement therapy (TRT) for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgenic steroids (AAS) within the general population has been appreciated. Both TRT and AAS can suppress the hypothalamic-pituitary-gonadal (HPG) axis resulting in diminution of spermatogenesis. Therefore, it is important that clinicians recognize previous TRT or AAS use in patients presenting for infertility treatment. Cessation of TRT or AAS use may result in spontaneous recovery of normal spermatogenesis in a reasonable number of patients if allowed sufficient time for recovery. However, some patients may not recover normal spermatogenesis or tolerate waiting for spontaneous recovery. In such cases, clinicians must be aware of the pathophysiologic derangements of the HPG axis related to TRT or AAS use and the pharmacologic agents available to reverse them. The available agents include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their off-label use is poorly described in the literature, potentially creating a knowledge gap for the clinician. Reviewing their use clinically for the treatment of hypogonadotropic hypogonadism and other HPG axis abnormalities can familiarize the clinician with the manner in which they can be used to recover spermatogenesis after TRT or AAS use.
  9,520 1,050 24
Current medical management of endocrine-related male infertility
Joshua D Ring, Aye A Lwin, Tobias S Köhler
May-June 2016, 18(3):357-363
Male factor contributes to 50%-60% of overall infertility but is solely responsible in only 20% of couples. Although most male factor infertility is ascertained from an abnormal semen analysis, other male factors can be contributory especially if the sample returns normal. Male infertility can be due to identifiable hormonal or anatomical etiologies that may be reversible or irreversible. This manuscript will highlight existing guidelines and our recommendations for hormone evaluation for male infertility and empiric therapies including multivitamins, estrogen receptor modulators (clomiphene), estrogen conversion blockers (anastrozole), and hormone replacement.
  9,097 1,077 18
Advances in the management of infertility in men with spinal cord injury
Emad Ibrahim, Nancy L Brackett, Charles M Lynne
May-June 2016, 18(3):382-390
DOI:10.4103/1008-682X.178851  PMID:27048781
Couples with a spinal cord injured male partner require assisted ejaculation techniques to collect semen that can then be further used in various assisted reproductive technology methods to achieve a pregnancy. The majority of men sustaining a spinal cord injury regardless of the cause or the level of injury cannot ejaculate during sexual intercourse. Only a small minority can ejaculate by masturbation. Penile vibratory stimulation and electroejaculation are the two most common methods used to retrieve sperm. Other techniques such as prostatic massage and the adjunct application of other medications can be used, but the results are inconsistent. Surgical sperm retrieval should be considered as a last resort if all other methods fail. Special attention must be paid to patients with T6 and rostral levels of injury due to the risk of autonomic dysreflexia resulting from stimulation below the level of injury. Bladder preparation should be performed before stimulation if retrograde ejaculation is anticipated. Erectile dysfunction is ubiquitous in the spinal cord injured population but is usually easily managed and does not pose a barrier to semen retrieval in these men. Semen analysis parameters of men with spinal cord injury are unique for this population regardless of the method of retrieval, generally presenting as normal sperm concentration but abnormally low sperm motility and viability. When sperm retrieval is desired in this population, emphasis should be placed on initially trying the simple methods of penile vibratory stimulation or electroejaculation before resorting to more advanced and invasive surgical procedures.
  8,429 607 22
An overview of the management of post-vasectomy pain syndrome
Wei Phin Tan, Laurence A Levine
May-June 2016, 18(3):332-337
DOI:10.4103/1008-682X.175090  PMID:26952956
Post-vasectomy pain syndrome remains one of the more challenging urological problems to manage. This can be a frustrating process for both the patient and clinician as there is no well-recognized diagnostic regimen or reliable effective treatment. Many of these patients will end up seeing physicians across many disciplines, further frustrating them. The etiology of post-vasectomy pain syndrome is not clearly delineated. Postulations include damage to the scrotal and spermatic cord nerve structures via inflammatory effects of the immune system, back pressure effects in the obstructed vas and epididymis, vascular stasis, nerve impingement, or perineural fibrosis. Post-vasectomy pain syndrome is defined as at least 3 months of chronic or intermittent scrotal content pain. This article reviews the current understanding of post-vasectomy pain syndrome, theories behind its pathophysiology, evaluation pathways, and treatment options.
  8,039 827 10
Recent advances in the genetics of testicular failure
Seung-Hun Song, Koji Chiba, Ranjith Ramasamy, Dolores J Lamb
May-June 2016, 18(3):350-355
DOI:10.4103/1008-682X.178857  PMID:27048782
Infertility affects approximately 15% of couples, and male factor is responsible for 30%-50% of all infertility. The most severe form of male infertility is testicular failure, and the typical phenotype of testicular failure is severely impaired spermatogenesis resulting in azoospermia or severe oligozoospermia. Although the etiology of testicular failure remains poorly understood, genetic factor typically is an underlying cause. Modern assisted reproductive techniques have revolutionized the treatment of male factor infertility, allowing biological fatherhood to be achieved by many men who would otherwise have been unable to become father to their children through natural conception. Therefore, identifying genetic abnormalities in male is critical because of the potential risk of transmission of genetic abnormalities to the offspring. Recently, along with other intense researches ongoing, whole-genome approaches have been used increasingly in the genetic studies of male infertility. In this review, we focus on the genetics of testicular failure and provide an update on the advances in the study of genetics of male infertility.
  6,750 776 29
Current updates on laboratory techniques for the diagnosis of male reproductive failure
Suresh C Sikka, Wayne JG Hellstrom
May-June 2016, 18(3):392-401
DOI:10.4103/1008-682X.179161  PMID:27056346
The incidence of male reproductive failure leading to infertility, whether due to delayed parenthood, environmental issues, genetic factors, drugs, etc., is increasing throughout the world. The diagnosis and prognosis of male subfertility have become a challenge. While the basic semen assessment has been performed for many years, a number of studies question the value of the traditional semen characteristics. This is partly due to inadequate methods and standardization, limited knowledge of technical requirements for quality assurance, and an incomplete understanding of what clinical information a semen assessment can provide. Laboratories currently performing semen and endocrine assessment show great variability. The World Health Organization (WHO) manual for the evaluation of semen has been the core of andrology and fertility evaluation that has helped in further development of this field over many years. These include the physical appearance of the ejaculate, assessments of sperm count, motility, vitality, morphology, and functional aspects of the sperm and semen sample. These tests also include male endocrine profile, biochemical evaluation of the semen, detection of antisperm antibodies in serum, the use of computer-aided sperm analysis (CASA), sperm DNA integrity, and its damage due to oxidative stress. Assisted reproductive techniques (e.g., IVF, ICSI) have shown great success but are too expensive. Further development in this field with newer techniques and extensive training/instructions can improve accuracy and reduce variability, thus maintaining the quality and standards of such an evaluation. There is an urgent need to have standardized training centers and increased awareness in this area of men's health for reproductive success.
  5,517 917 16
Vacuum therapy in penile rehabilitation after radical prostatectomy: review of hemodynamic and antihypoxic evidence
Sheng-Qiang Qian, Liang Gao, Qiang Wei, Jiuhong Yuan
May-June 2016, 18(3):446-451
DOI:10.4103/1008-682X.159716  PMID:26289397
Generally, hypoxia is a normal physiological condition in the flaccid penis, which is interrupted by regular nocturnal erections in men with normal erectile function. [1] Lack of spontaneous and nocturnal erections after radical prostatectomy due to neuropraxia results in persistent hypoxia of cavernosal tissue, which leads to apoptosis and degeneration of cavernosal smooth muscle fibers. Therefore, overcoming hypoxia is believed to play a crucial role during neuropraxia. The use of a vacuum erectile device (VED) in penile rehabilitation is reportedly effective and may prevent loss of penile length. The corporal blood after VED use is increased and consists of both arterial and venous blood, as revealed by color Doppler sonography and blood gas analysis. A similar phenomenon was observed in negative pressure wound therapy (NPWT). However, NPWT employs a lower negative pressure than VED, and a hypoperfused zone, which increases in response to negative pressure adjacent to the wound edge, was observed. Nonetheless, questions regarding ideal subatmospheric pressure levels, modes of action, and therapeutic duration of VED remain unanswered. Moreover, it remains unclear whether a hypoperfused zone or PO 2 gradient appears in the penis during VED therapy. To optimize a clinical VED protocol in penile rehabilitation, further research on the mechanism of VED, especially real-time PO 2 measurements in different parts of the penis, should be performed.
  5,701 570 2
Reprogrammed CRISPR-Cas9 targeting the conserved regions of HPV6/11 E7 genes inhibits proliferation and induces apoptosis in E7-transformed keratinocytes
Yu-Chen Liu, Zhi-Ming Cai, Xue-Jun Zhang
May-June 2016, 18(3):475-479
DOI:10.4103/1008-682X.157399  PMID:26228041
The persistence infection of low-risk type (type 6 or type 11) of human papillomavirus (HPV) is the main cause of genital warts. Given the high rate of recurrence after treatment, the use of a new molecular agent is certain to be of value. The aim of this study was to achieve targeted inactivation of viral E 7 gene in keratinocytes using the reprogrammed clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 system. To accomplish this, a universal CRISPR-Cas9 system for targeting both HPV6/11 E 7 genes was constructed by using a dual guide RNA vector. After transfection of the vector into E 7-transfromed keratinocytes, the expression level of E 7 protein was measured using western-blot analysis and the sequence of the E 7 gene was determined using Sanger sequencing. Cell proliferation was analyzed by CCK-8 assay, and cell apoptosis was evaluated by Hoechst 33258 staining, flow cytometry analysis and ELISA assay. The results indicated that both HPV6/11 E 7 genes can be inactivated by the single CRISPR-Cas9 system. Furthermore, silencing of E 7 led to inhibition of cell proliferation and induction of apoptosis in E 7-transfromed keratinocytes but not in normal keratinocytes. Our data suggested that the reprogrammed CRISPR-Cas9 system has the potential for the development of an adjuvant therapy for genital warts.
  5,250 747 19
Seminal biomarkers for the evaluation of male infertility
Jared M Bieniek, Andrei P Drabovich, Kirk C Lo
May-June 2016, 18(3):426-433
DOI:10.4103/1008-682X.175781  PMID:26975492
For men struggling to conceive with their partners, diagnostic tools are limited and often consist of only a standard semen analysis. This baseline test serves as a crude estimation of male fertility, leaving patients and clinicians in need of additional diagnostic biomarkers. Seminal fluid contains the highest concentration of molecules from the male reproductive glands, therefore, this review focuses on current and novel seminal biomarkers in certain male infertility scenarios, including natural fertility, differentiating azoospermia etiologies, and predicting assisted reproductive technique success. Currently available tests include antisperm antibody assays, DNA fragmentation index, sperm fluorescence in situ hybridization, and other historical sperm functional tests. The poor diagnostic ability of current assays has led to continued efforts to find more predictive biomarkers. Emerging research in the fields of genomics, epigenetics, proteomics, transcriptomics, and metabolomics holds promise for the development of novel male infertility biomarkers. Seminal protein-based assays of TEX101, ECM1, and ACRV1 are already available or under final development for clinical use. Additional panels of DNA, RNA, proteins, or metabolites are being explored as we attempt to understand the pathophysiologic processes of male infertility. Future ventures will need to continue data integration and validation for the development of clinically useful infertility biomarkers to aid in male infertility diagnosis, treatment, and counseling.
  4,674 1,216 40
Vasectomy reversal: a clinical update
Abhishek P Patel, Ryan P Smith
May-June 2016, 18(3):365-371
DOI:10.4103/1008-682X.175091  PMID:26975488
Vasectomy is a safe and effective method of contraception used by 42-60 million men worldwide. Approximately 3%-6% of men opt for a vasectomy reversal due to the death of a child or divorce and remarriage, change in financial situation, desire for more children within the same marriage, or to alleviate the dreaded postvasectomy pain syndrome. Unlike vasectomy, vasectomy reversal is a much more technically challenging procedure that is performed only by a minority of urologists and places a larger financial strain on the patient since it is usually not covered by insurance. Interest in this procedure has increased since the operating microscope became available in the 1970s, which consequently led to improved patency and pregnancy rates following the procedure. In this clinical update, we discuss patient evaluation, variables that may influence reversal success rates, factors to consider in choosing to perform vasovasostomy versus vasoepididymostomy, and the usefulness of vasectomy reversal to alleviate postvasectomy pain syndrome. We also review the use of robotics for vasectomy reversal and other novel techniques and instrumentation that have emerged in recent years to aid in the success of this surgery.
  5,109 710 13
Comparison of two adjuvant hormone therapy regimens in patients with high-risk localized prostate cancer after radical prostatectomy: primary results of study CU1005
Kun Chang, Xiao-Jian Qin, Hai-Liang Zhang, Bo Dai, Yao Zhu, Guo-Hai Shi, Yi-Jun Shen, Yi-Ying Zhu, Ding-Wei Ye
May-June 2016, 18(3):452-455
DOI:10.4103/1008-682X.160884  PMID:26323560
The role of adjuvant hormonal therapy and optimized regimens for high-risk localized prostate cancer after radical prostatectomy remains controversial. Herein, the clinical trial CU1005 prospectively evaluated two regimens of maximum androgen blockage  or bicalutamide 150 mg daily as immediate adjuvant therapy for high-risk localized prostate cancer. Overall, 209 consecutive patients were recruited in this study, 107 of whom received 9 months of adjuvant maximum androgen blockage, whereas 102 received 9 months of adjuvant bicalutamide 150 mg. The median postoperative follow-up time was 27.0 months. The primary endpoint was biochemical recurrence. Of the 209 patients, 59 patients developed biochemical recurrence. There was no difference between the two groups with respect to clinical characteristics, including age, pretreatment prostate-specific antigen, Gleason score, surgical margin status, or pathological stages. The maximum androgen blockage group experienced longer biochemical recurrence-free survival (P = 0.004) compared with the bicalutamide 150 mg group. Side-effects in the two groups were similar and could be moderately tolerated in all patients. In conclusion, immediate, 9-month maximum androgen blockage should be considered as an alternative to bicalutamide 150 mg as adjuvant treatment for high-risk localized prostate cancer patients after radical prostatectomy.
  4,256 498 1
Infertility, impotence, and emasculation - psychosocial contexts for abandoning reproduction
Erik Wibowo, Thomas W Johnson, Richard J Wassersug
May-June 2016, 18(3):403-408
DOI:10.4103/1008-682X.173937  PMID:26924280
From a Darwinian perspective we live to reproduce, but in various situations genetic males elect not to reproduce by choosing medical treatments leading to infertility, impotence, and, in the extreme, emasculation. For many men, infertility can be psychologically distressing. However, for certain genetic males, being infertile may improve their quality of life. Examples include (1) men who seek vasectomy, (2) individuals with Gender Dysphoria (e.g., transwomen, and modern day voluntary eunuchs), (3) most gay men, and (4) men treated for testicular and prostate cancer. Men who desire vasectomy typically have a Darwinian fitness W >1 at the time of their vasectomies; i.e., after they have their desired number of offspring or consider themselves past an age for parenting newborns. In contrast, prostate and testicular cancer patients, along with individuals with extreme Gender Dysphoria, do not necessarily seek to be sterile, but accept it as an unavoidable consequence of the treatment for their condition undertaken for survival (in case of cancer patients) or to achieve a better quality of life (for those with Gender Dysphoria). Most gay men do not father children, but they may play an avuncular role, providing for their siblings' offspring's welfare, thus improving their inclusive fitness through kin selection. In a strictly Darwinian model, the primary motivation for all individuals is to reproduce, but there are many situations for men to remove themselves from the breeding populations because they have achieved a fitness W ≥1, or have stronger medical or psychological needs that preclude remaining fertile.
  3,985 470 2
Paternal aging and increased risk of congenital disease, psychiatric disorders, and cancer
Simon L Conti, Michael L Eisenberg
May-June 2016, 18(3):420-424
DOI:10.4103/1008-682X.175097  PMID:26975491
As couples are increasingly delaying parenthood, the effect of the aging men and women on reproductive outcomes has been an area of increased interest. Advanced paternal age has been shown to independently affect the entire spectrum of male fertility as assessed by reductions in sperm quality and fertilization (both assisted and unassisted). Moreover, epidemiological data suggest that paternal age can lead to higher rates of adverse birth outcomes and congenital anomalies. Mounting evidence also suggests increased risk of specific pediatric and adult disease states ranging from cancer to behavioral traits. While disease states associated with advancing paternal age have been well described, consensus recommendations for neonatal screening have not been as widely implemented as have been with advanced maternal age.
  3,679 538 15
Prostate-specific antigen density predicts favorable pathology and biochemical recurrence in patients with intermediate-risk prostate cancer
Ho Won Kang, Hae Do Jung, Joo Yong Lee, Jong Kyou Kwon, Seong Uk Jeh, Kang Su Cho, Won Sik Ham, Young Deuk Choi
May-June 2016, 18(3):480-484
DOI:10.4103/1008-682X.154313  PMID:26178393
This study was designed to identify clinical predictors of favorable pathology and biochemical recurrence (BCR) in patients with intermediate-risk prostate cancer (IRPCa). Between 2006 and 2012, clinicopathological and oncological data from 203 consecutive men undergoing robot-assisted radical prostatectomy (RARP) for IRPCa were reviewed in a single-institutional retrospective study. Favorable pathology was defined as Gleason score ≤6 and organ-confined cancer as detected by surgical pathology. Logistic regression analysis was used to determine predictive variables of favorable pathology, and the Kaplan-Meier and multivariate Cox regression model were used to estimate BCR-free survival after RARP. Overall, 38 patients (18.7%) had favorable pathology after RARP. Lower quartile prostate-specific antigen density (PSAD) was associated with favorable pathology compared to the highest quartile PSAD after adjusting for preoperative PSA, clinical stage and biopsy Gleason score (odds ratio, 5.42; 95% confidence interval, 1.01-28.97; P = 0.048). During a median 37.8 (interquartile range, 24.6-60.2) months of follow-up, 66 patients experienced BCR. There were significant differences with regard to BCR free survival by PSAD quartiles (log rank, P = 0.003). Using a multivariable Cox proportion hazard model, PSAD was found to be an independent predictor of BCR in patients with IRPCa after RARP (hazard ratio, 4.641; 95% confidence interval, 1.109-19.417; P = 0.036). The incorporation of the PSAD into risk assessments might provide additional prognostic information and identify some patients in whom active surveillance would be appropriate in patients with IRPCa.
  3,133 404 5
Active immunization with GnRH-tandem-dimer peptide in young male rats reduces serum reproductive hormone concentrations, testicular development and spermatogenesis
Xing-Fa Han, Jun-Li Li, Yu-Qin Zhou, Xiao-Hua Ren, Gong-Cheng Liu, Xiao-Han Cao, Xiao-Gang Du, Xian-Yin Zeng
May-June 2016, 18(3):485-491
DOI:10.4103/1008-682X.156856  PMID:26208395
GnRH sterilization vaccines have been developed for various practical and clinical reasons. However, conjugation of GnRH peptide to carrier protein has many drawbacks, hampering the further commercialization of GnRH vaccines. In this study, a new nonconjugated GnRH vaccine, D-Lys6-GnRH-tandem-dimer peptide (TDK), emulsified in Specol adjuvant was investigated for its immunocastration efficacy in young male rats. Prepubertal male rats were randomly allocated into three groups (n = 12): control (no treatment), surgically castrated or immunized against 100 μg TDK in Specol adjuvant at 6 weeks of age (with a booster 8 weeks later). Blood samples (for antibody titers and hormone concentrations) were collected at 2-week intervals until rats were killed (18 weeks of age). Compared to intact controls, active immunization against TDK reduced (P < 0.05) serum concentrations of testosterone, inhibin B, LH and FSH, prevented the onset of spermatogenesis at puberty. Furthermore, mRNA expressions of GnRH receptor, LH-β and FSH-β in the pituitary, LH receptor, FSH receptor, inhibin α, βA and βB subunit in the testes were decreased in immunocastrated rats compared to intact controls (P < 0.05). These results demonstrate for the first time that GnRH-tandem-dimer peptide emulsified in Specol is a promising veterinary sterilization medicine.
  3,092 444 5
Androgen receptor splice variants and polycystic ovary syndrome: cause or effect?
Kirsty A Walters, David J Handelsman
May-June 2016, 18(3):442-443
DOI:10.4103/1008-682X.161600  PMID:26306851
  3,012 440 5
Insurance coverage for male infertility care in the United States
James M Dupree
May-June 2016, 18(3):339-341
DOI:10.4103/1008-682X.177838  PMID:27030084
Infertility is a common condition experienced by many men and women, and treatments are expensive. The World Health Organization and American Society of Reproductive Medicine define infertility as a disease, yet private companies infrequently offer insurance coverage for infertility treatments. This is despite the clear role that healthcare insurance plays in ensuring access to care and minimizing the financial burden of expensive services. In this review, we assess the current knowledge of how male infertility care is covered by insurance in the United States. We begin with an appraisal of the costs of male infertility care, then examine the state insurance laws relevant to male infertility, and close with a discussion of why insurance coverage for male infertility is important to both men and women. Importantly, we found that despite infertility being classified as a disease and males contributing to almost half of all infertility cases, coverage for male infertility is often excluded from health insurance laws. Excluding coverage for male infertility places an undue burden on their female partners. In addition, excluding care for male infertility risks missing opportunities to diagnose important health conditions and identify reversible or irreversible causes of male infertility. Policymakers should consider providing equal coverage for male and female infertility care in future health insurance laws.
  2,852 546 5
Annexin A5 regulates Leydig cell testosterone production via ERK1/2 pathway
Ze He, Qin Sun, Yuan-Jiao Liang, Li Chen, Yi-Feng Ge, Shi-Feng Yun, Bing Yao
May-June 2016, 18(3):456-461
DOI:10.4103/1008-682X.160260  PMID:26289400
This study was to investigate the effect of annexin A5 on testosterone secretion from primary rat Leydig cells and the underlying mechanisms. Isolated rat Leydig cells were treated with annexin A5. Testosterone production was detected by chemiluminescence assay. The protein and mRNA of Steroidogenic acute regulatory (StAR), P450scc, 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD), and 17α-hydroxylase were examined by Western blotting and semi-quantitative RT-PCR, respectively. Annexin A5 significantly stimulated testosterone secretion from rat Leydig cells in dose- and time-dependent manners and increased mRNA and protein expression of StAR, P450scc, 3β-HSD, and 17β-HSD but not 17α-hydroxylase. Annexin A5 knockdown by siRNA significantly decreased the level of testosterone and protein expression of P450scc, 3β-HSD, and 17β-HSD. The significant activation of ERK1/2 signaling was observed at 5, 10, and 30 min after annexin A5 treatment. After the pretreatment of Leydig cells with ERK inhibitor PD98059 (50 μmol l−1 ) for 20 min, the effects of annexin A5 on promoting testosterone secretion and increasing the expression of P450scc, 3β-HSD, and 17β-HSD were completely abrogated (P < 0.05). Thus, ERK1/2 signaling is involved in the roles of annexin A5 in mediating testosterone production and the expression of P450scc, 3β-HSD, and 17β-HSD in Leydig cells.
  2,925 426 8
The effect of the degree of left renal vein constriction on the development of adolescent varicocele in Sprague-Dawley rats
Bing Yao, Wen-Liang Zhou, Da-Yu Han, Bin Ouyang, Xu Chen, Sheng-Fu Chen, Chun-Hua Deng, Xiang-Zhou Sun
May-June 2016, 18(3):471-474
DOI:10.4103/1008-682X.157398  PMID:26262773
Experimental models have allowed inquiry into the pathophysiology of varicocele (VC) beyond that possible with human patients. A randomized controlled study in rats was designed to clarify the influence of the degree of left renal vein constriction on the development of adolescent VC. Fifty adolescent male Sprague-Dawley rats (Rattus norvegicus) were randomly assigned to five groups of 10: the experimental groups (I-IV) underwent partial ligation of left renal veins with 0.5-, 0.6-, 0.7-, and 0.8-mm diameter needles, respectively. The control group (V) underwent a sham operation. The diameter of the left spermatic vein (LSV) was measured at baseline and 30 days postoperatively. In addition, the lesion of the left kidney was examined with the naked eye and assessed by Masson's trichrome staining. VC was successfully induced in 2 (20%), 4 (40%), 7 (70%), and 10 (100%) rats in groups I-IV, respectively. The other rats failed to develop VCs primarily due to left renal atrophy. No VC was observed in group V. The postsurgical LSV diameters in VC rats in groups III and IV were 1.54 ± 0.16 and 1.49 ± 0.13 mm, respectively (P > 0.05), and their increments were 1.36 ± 0.10 and 1.31 ± 0.10 mm, respectively (P > 0.05). These results suggest that suitable constriction of the left renal vein is critical for adolescent VC development. In addition, the 0.8-mm diameter needle may be more suitable for inducing left renal vein constriction in adolescent rat models.
  2,929 405 3
Varicocele management in the era of in vitro fertilization/intracytoplasmic sperm injection
Piyush Pathak, Aravind Chandrashekar, Tariq S Hakky, Alexander W Pastuszak
May-June 2016, 18(3):343-348
DOI:10.4103/1008-682X.178482  PMID:27030086
Varicocele is the most common surgically treatable cause of male infertility, and often results in alterations in semen parameters, sperm DNA damage, and changes to the seminal milieu. Varicocele repair can result in improvement in these parameters in the majority of men with clinical varicocele; data supporting repair in men with subclinical varicocele are less definitive. In couples seeking fertility using assisted reproductive technologies (ARTs), varicocele repair may offer improvement in semen parameters and sperm health that can increase the likelihood of successful fertilization using techniques such as in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), or may decrease the level of ART needed to achieve successful pregnancy. Male infertility is an indicator of general male health, and evaluation of the infertile male with an eye toward future health can facilitate optimal screening and treatment of these men. Furthermore, varicocele may represent a progressive lesion, offering an argument for its repair, although this is currently unclear.
  2,712 537 16
One-stage dorsal lingual mucosal graft urethroplasty for the treatment of failed hypospadias repair
Hong-Bin Li, Yue-Min Xu, Qiang Fu, Ying-Long Sa, Jiong Zhang, Hong Xie
May-June 2016, 18(3):467-470
DOI:10.4103/1008-682X.157545  PMID:26228042
The aim of this study was to retrospectively investigate the outcomes of patients who underwent one-stage onlay or inlay urethroplasty using a lingual mucosal graft (LMG) after failed hypospadias repairs. Inclusion criteria included a history of failed hypospadias repair, insufficiency of the local skin that made a reoperation with skin flaps difficult, and necessity of an oral mucosal graft urethroplasty. Patients were excluded if they had undergone a failed hypospadias repair using the foreskin or a multistage repair urethroplasty. Between January 2008 and December 2012, 110 patients with failed hypospadias repairs were treated in our center. Of these patients, 56 underwent a one-stage onlay or inlay urethroplasty using LMG. The median age was 21.8 years (range: 4-45 years). Of the 56 patients, one-stage onlay LMG urethroplasty was performed in 42 patients (group 1), and a modified Snodgrass technique using one-stage inlay LMG urethroplasty was performed in 14 (group 2). The median LMG urethroplasty length was 5.6 ± 1.6 cm (range: 4-13 cm). The mean follow-up was 34.7 months (range: 10-58 months), and complications developed in 12 of 56 patients (21.4%), including urethrocutaneous fistulas in 7 (6 in group 1, 1 in group 2) and neourethral strictures in 5 (4 in group 1, 1 in group 2). The total success rate was 78.6%. Our survey suggests that one-stage onlay or inlay urethroplasty with LMG may be an effective option to treat the patients with less available skin after failed hypospadias repairs; LMG harvesting is easy and safe, irrespective of the patient's age.
  2,813 423 3
Use of early chemotherapy for hormone-sensitive prostate cancer: time for CHAARTED
Jeanny B Aragon-Ching
May-June 2016, 18(3):444-445
DOI:10.4103/1008-682X.164920  PMID:26510505
  2,579 497 -
Metastasis to scrotal skin as the initial manifestation in a patient with rectal adenocarcinoma: a rare case report and literature review
Gang Wu, Bao-Jun Gu, Kent L Nastiuk, Jun Gu, Deng-Long Wu
May-June 2016, 18(3):492-493
DOI:10.4103/1008-682X.157394  PMID:26178397
  2,667 385 1
Stem cells, gene therapy, and advanced medical management hold promise in the treatment of male infertility
Ryan P Smith, Larry I Lipshultz, Jason R Kovac
May-June 2016, 18(3):364-364
DOI:10.4103/1008-682X.179249  PMID:27056350
  2,549 475 1
Vasectomy reversal and other strategies to mitigate postvasectomy pain syndrome
Ryan P Smith, Larry I Lipshultz, Jason R Kovac
May-June 2016, 18(3):338-338
DOI:10.4103/1008-682X.179243  PMID:27056347
  2,439 519 -
Basic concepts and recent advancements in the study of male fertility
Jason R Kovac, Larry I Lipshultz
May-June 2016, 18(3):331-331
DOI:10.4103/1008-682X.179141  PMID:27048783
  2,207 715 1
A case of giant epidermoid cyst on the penis
Hong-Jie Chen, Wu Li, Yuan-Ming Han, Kuan-Yu Che
May-June 2016, 18(3):494-495
DOI:10.4103/1008-682X.157547  PMID:26178400
  2,447 363 2
Outcomes of 13 ICSI-PGD cycles with ejaculated spermatozoa in patients with Klinefelter syndrome
Tian-Xiang Ni, Jun-Hao Yan, Bo Wang, Yue-Ting Zhu, Hong-Chang Li, Hong-Qiang Xie, Wen-Jie Jiang, Zi-Jiang Chen
May-June 2016, 18(3):498-499
DOI:10.4103/1008-682X.161238  PMID:26365720
  2,277 379 2
Sperm morphology and reproductive success
Jason R Kovac, Larry I Lipshultz
May-June 2016, 18(3):402-402
DOI:10.4103/1008-682X.179253  PMID:27048790
  2,072 534 -
Advancement of male health is dependent upon updates to insurance coverage for infertility in the United States
Ryan P Smith, Larry I Lipshultz, Jason R Kovac
May-June 2016, 18(3):342-342
DOI:10.4103/1008-682X.179244  PMID:27048787
  2,091 422 -
Morphological and microcirculatory evaluation of the rat testis after detorsion with or without a capsular release with a tunica vaginalis flap
Tamás Józsa, Zoltán Klárik, Ferenc Kiss, Eniko Tóth, Anita Mester, Zoltán Hargitai, Yi-Che Changchien, Magdalena Fossum, Norbert Németh
May-June 2016, 18(3):462-466
DOI:10.4103/1008-682X.157546  PMID:26178399
Testicular torsion may lead to serious ischemia, and the viability depends on the duration of torsion and the effect of ischemia-reperfusion. Testicular decompression and tunica vaginalis flap application technique were introduced in 2008 by Kutikov et al. We aimed to examine the impact of this method on the testicular microcirculation and hemorheological parameters in a rat model. Six adult rats underwent bilateral scrotal exploration. Intravaginal torsion of the testis was created by 720° rotation on both sides for 2 h. After detorsion, the right testes underwent tunica albuginea incision and tunica vaginalis flap application. Testicular microcirculation was monitored and hematological parameters, erythrocyte deformability, and aggregation were determined. Measurements were performed before and after torsion, directly after detorsion, on the 1 st -2 nd and 8 th postoperative day. After the last sampling, testicles were removed to determine their volume for histological examinations. The microcirculatory parameters demonstrated slight differences between testicles. Apical zone of the left (nondecompressed) testicles had elevated compared to the middle zone (P < 0.05). On the 2 nd and 8 th day, the microcirculation of the testes normalized but not equally. The erythrocyte aggregation and deformability decreased by the 8 th day. Both testicles underwent atrophy and epithelial necrosis, but the volume of the decompressed ones was lower (1.07 ± 0.08 vs 1.25 ± 0.31). Histologically, there was no significant difference in epithelial damage score between decompressed and nondecompressed testes. In conclusion, 2-h ischemia led to alteration in testicular microcirculation, reduction in volume, changes in hemorheological parameters and serious epithelial necrosis both in decompressed and nondecompressed testicles without remarkable differences.
  2,227 280 4
Is varicocele repair necessary, given the advanced state of assisted reproductive technologies?
Ryan P Smith, Larry I Lipshultz, Jason R Kovac
May-June 2016, 18(3):349-349
DOI:10.4103/1008-682X.179245  PMID:27056348
  2,098 404 1
Estradiol exerts alterations in sexual function and fertility in human males
Ryan P Smith, Larry I Lipshultz, Jason R Kovac
May-June 2016, 18(3):441-441
DOI:10.4103/1008-682X.179157  PMID:27048785
  2,015 427 1
The role of advanced paternal age in modern reproductive medicine
Christopher Wu, Larry I Lipshultz, Jason R Kovac
May-June 2016, 18(3):425-425
DOI:10.4103/1008-682X.179251  PMID:27056352
  1,968 460 4
The importance of understanding baseline reproductive function prior to the administration of exogenous testosterone
Jason R Kovac, Larry I Lipshultz
May-June 2016, 18(3):381-381
DOI:10.4103/1008-682X.179142  PMID:27048784
  2,028 355 -
Can radical prostatectomy shortly after prostate biopsy affect intra-operative and postoperative outcomes?
Lucio Dell'Atti, Gaetano Capparelli, Stefano Papa, Carmelo Ippolito
May-June 2016, 18(3):496-497
DOI:10.4103/1008-682X.165949  PMID:26510507
  2,176 102 1
Are genetic biomarkers the future of male fertility testing?
Jason R Kovac, Larry I Lipshultz
May-June 2016, 18(3):356-356
DOI:10.4103/1008-682X.179246  PMID:27056349
  1,846 416 -
The benefits of understanding complementary medicine options for patients with male factor infertility
Christopher Wu, Larry I Lipshultz, Jason R Kovac
May-June 2016, 18(3):419-419
DOI:10.4103/1008-682X.179250  PMID:27056351
  1,885 370 -
Azoospermia and the cancer patient: are there any options?
Jason R Kovac, Larry I Lipshultz
May-June 2016, 18(3):409-409
DOI:10.4103/1008-682X.179248  PMID:27048789
  1,849 354 -
Factors to consider for informed consent prior to vasectomy reversal
Jason R Kovac, Larry I Lipshultz
May-June 2016, 18(3):372-372
DOI:10.4103/1008-682X.179156  PMID:27056345
  1,914 265 -
Use of testicular sperm to combat the negative effects of DNA fragmentation
Jason R Kovac, Larry I Lipshultz
May-June 2016, 18(3):434-434
DOI:10.4103/1008-682X.179158  PMID:27048786
  1,775 373 1
Corrigendum to "Relapse of prostate cancer from the viewpoint of total gland volume kinetics theory" by Hiroki Watanabe
Hiroki Watanabe
May-June 2016, 18(3):500-500
DOI:10.4103/1008-682X.175788  PMID:27004540
  1,788 308 -
The importance of sexual function in men with spinal cord injuries
Jason R Kovac, Larry I Lipshultz
May-June 2016, 18(3):391-391
DOI:10.4103/1008-682X.179247  PMID:27048788
  1,621 352 1