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  Citation statistics : Table of Contents
   2015| September-October  | Volume 17 | Issue 5  
    Online since August 27, 2015

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Epididymosomes: a heterogeneous population of microvesicles with multiple functions in sperm maturation and storage
Robert Sullivan
September-October 2015, 17(5):726-729
DOI:10.4103/1008-682X.155255  PMID:26112475
Extracellular microvesicles present in the epididymal fluid have been named epididymosomes. Many epididymosome-associated proteins are transferred to spermatozoa during their maturation in the excurrent duct. Epididymosomes are heterogeneous, with their size varying between 50 and 250 nm. Two distinct population of epididymosomes characterized by different protein compositions and diameters have been isolated from the bovine epididymal fluid using different centrifugation protocols. One subpopulation of epididymosomes was characterized by CD9 and other tetraspanin partners. Transfer of proteins from these epididymosomes to maturing spermatozoa in co-incubation experiments was inhibited by antibodies against tetraspanin proteins. This suggests that this subpopulation of epididymosomes is involved in the acquisition of proteins involved in maturation by spermatozoa in the epididymis. The other population of epididymosomes was characterized by ELSPBP1 (epididymal sperm binding protein 1), known for its affinity for the phospholipid choline group. Flow cytometric analyses showed that ELSPBP1-positive epididymosomes only interacted with dying or dead epididymal spermatozoa in a Zn 2 + -dependent manner. BLVRA (biliverdin reductase) was identified as a partner of ELSPBP1. This enzyme reduces biliverdin to bilirubin: two molecules with powerful anti-oxidant properties. We hypothesize that BLVRA is involved in an ROS-scavenging mechanism protecting live epididymal spermatozoa against detrimental molecules (ROS) released by dying cells. Therefore, it appears that there are at least two epididymosome population with distinct functions: targeting specific proteins to transiting spermatozoa by tetraspanin-mediated membrane fusion, and protection of epididymal spermatozoa against ROS released from dying cells. Further work is needed to understand functions of epididymosomes in epididymal physiology and sperm maturation and storage.
  22 5,062 597
Extracellular microRNAs from the epididymis as potential mediators of cell-to-cell communication
Clémence Belleannée
September-October 2015, 17(5):730-736
DOI:10.4103/1008-682X.155532  PMID:26178395
Ribonucleic acid (RNA) was previously thought to remain inside cells as an intermediate between genes and proteins during translation. However, it is now estimated that 98% of the mammalian genomic output is transcribed as noncoding RNAs, which are involved in diverse gene expression regulatory mechanisms and can be transferred from one cell to another through extracellular communication. For instance, microRNAs are 22-nucleotide-long noncoding RNAs that are generated by endonuclease cleavage of precursors inside the cells and are secreted as extracellular microRNAs to regulate target cell posttranscriptional gene expression via RNA interference. We and others have shown that different populations of microRNAs are expressed in distinct regions of the human epididymis and regulate the expression of target genes that are involved in the control of male fertility as indicated by knock-out mouse models. Importantly, some microRNAs, including the microRNA-888 (miR-888) cluster that is exclusively expressed in the reproductive system of human and nonhuman primates, are released in the sperm-surrounding fluid in the epididymis via extracellular vesicles, the so-called epididymosomes. In addition to interacting with the membrane of maturing spermatozoa, these extracellular vesicles containing microRNAs communicate with epithelial cells located downstream from their release site, suggesting a role in the luminal exocrine control of epididymal functions. Apart from their potential roles as mediators of intercellular communication within the epididymis, these extracellular microRNAs are potent molecular targets for the noninvasive diagnosis of male infertility.
  13 4,366 519
Epididymitis: revelations at the convergence of clinical and basic sciences
Vera Michel, Adrian Pilatz, Mark P Hedger, Andreas Meinhardt
September-October 2015, 17(5):756-763
DOI:10.4103/1008-682X.155770  PMID:26112484
Acute epididymitis represents a common medical condition in the urological outpatient clinic. Mostly, epididymitis is caused by bacterial ascent through the urogenital tract, with pathogens originating either from sexually transmitted diseases or urinary tract infections. Although conservative antimicrobial therapy is possible in the majority of patients and is usually sufficient to eradicate the pathogen, studies have shown persistent oligozoospermia and azoospermia in up to 40% of these patients. Animal models of epididymitis are created to delineate the underlying reasons for this observation and the additional impairment of sperm function that is often associated with the disease. Accumulated data provide evidence of a differential expression of immune cells, immunoregulatory genes and pathogen-sensing molecules along the length of the epididymal duct. The evidence suggests that a tolerogenic environment exists in the caput epididymidis, but that inflammatory responses are most intense toward the cauda epididymidis. This is consistent with the need to provide protection for the neo-antigens of spermatozoa emerging from the testis, without compromising the ability to respond to ascending infections. However, severe inflammatory responses, particularly in the cauda, may lead to collateral damage to the structure and function of the epididymis. Convergence of the clinical observations with appropriate animal studies should lead to better understanding of the immunological environment throughout the epididymis, the parameters underlying susceptibility to epididymitis, and to therapeutic approaches that can mitigate epididymal damage and subsequent fertility problems.
  10 7,065 623
From the epididymis to the egg: participation of CRISP proteins in mammalian fertilization
Vanina G Da Ros, Mariana Weigel Muñoz, Maria A Battistone, Nicolás G Brukman, Guillermo Carvajal, Ludmila Curci, Matías D Gómez-Elías, Débora J Cohen, Patricia S Cuasnicu
September-October 2015, 17(5):711-715
DOI:10.4103/1008-682X.155769  PMID:26112483
Mammalian fertilization is a complex process that involves different steps of interaction between the male and female gametes. In spite of its relevance, the molecular mechanisms underlying this process still remain to be elucidated. The present review describes the contribution of our laboratory to the understanding of mammalian fertilization using Cysteine-RIch Secretory Proteins (CRISP) as model molecules. Substantial evidence obtained from in vitro assays and knockout models shows that epididymal CRISP1 associates with the sperm surface with two different affinities during maturation, and participates in the regulation of signaling pathways during capacitation as well as in both sperm-zona pellucida interaction and gamete fusion. These observations can be extended to humans as judged by our findings showing that the human homolog of the rodent protein (hCRISP1) is also involved in both stages of fertilization. Evidence supports that other members of the CRISP family secreted in the testis (CRISP2), epididymis (CRISP3-4) or during ejaculation (CRISP3) are also involved in sperm-egg interaction, supporting the existence of a functional redundancy and cooperation between homolog proteins ensuring the success of fertilization. Together, our observations indicate that CRISP proteins accompany spermatozoa along their transit through both the male and female reproductive tracts. We believe these results not only contribute to a better mechanistic understanding of fertilization but also support CRISP proteins as excellent candidates for future research on infertility and contraception.
  9 6,064 570
Epididymosomes: transfer of fertility-modulating proteins to the sperm surface
Patricia A Martin-DeLeon
September-October 2015, 17(5):720-725
DOI:10.4103/1008-682X.155538  PMID:26112481
A variety of glycosylphosphatidylinositol (GPI)-linked proteins are acquired on spermatozoa from epididymal luminal fluids (ELF) during sperm maturation. These proteins serve roles in immunoprotection and in key steps of fertilization such as capacitation, acrosomal exocytosis and sperm-egg interactions. Their acquisition on sperm cells is mediated both by membrane vesicles (epididymosomes, EP) which were first reported to dock on the sperm surface, and by lipid carriers which facilitate the transfer of proteins associated with the membrane-free fraction of ELF. While the nonvesicular fraction is more efficient, both pathways are dependent on hydrophobic interactions between the GPI-anchor and the external lipid layer of the sperm surface. More recently proteomic and hypothesis-driven studies have shown that EP from several mammals carry transmembrane (TM) proteins, including plasma membrane Ca 2 + -ATPase 4 (PMCA4). Synthesized in the testis, PMCA4 is an essential protein and the major Ca 2 + efflux pump in murine spermatozoa. Delivery of PMCA4 to spermatozoa from bovine and mouse EP during epididymal maturation and in vitro suggests that the docking of EP on the sperm surface precedes fusion, and experimental evidence supports a fusogenic mechanism for TM proteins. Fusion is facilitated by CD9, which generates fusion-competent sites on membranes. On the basis of knowledge of PMCA4's interacting partners a number of TM and membrane-associated proteins have been identified or are predicted to be present, in the epididymosomal cargo deliverable to spermatozoa. These Ca 2 + -dependent proteins, undetected in proteomic studies, play essential roles in sperm motility and fertility, and their detection highlights the usefulness of the hypothesis-driven approach.
  7 4,853 470
Spermatogonial stem cells: Progress and prospects
Mitsuru Komeya, Takehiko Ogawa
September-October 2015, 17(5):771-775
DOI:10.4103/1008-682X.154995  PMID:25994650
Twenty years ago, the transplantation of spermatogonial stem cells (SSCs) from a mouse to other recipient mice was shown to be feasible, which clearly demonstrated the functional identity of SSCs. Since then, several important new findings and other technical developments have followed, which included a new hypothesis on their cell kinetics and spermatogonial hierarchy in the testis, a culture method allowing their self-renewal and proliferation, a testis tissue organ culture method, which induced their complete differentiation up to sperm, and the in vitro induction of germ cells from embryonic stem cells and induced pluripotent stem cells. These advancements reinforced or advanced our understanding of this unique cell. Nonetheless, there are many unresolved questions in the study of spermatogonial stem cells and a long road remains until these cells can be used clinically in reproductive medicine.
  7 5,071 679
Posttesticular sperm maturation, infertility, and hypercholesterolemia
Marjorie Whitfield, Xavier Pollet-Villard, Rachel Levy, Joël R Drevet, Fabrice Saez
September-October 2015, 17(5):742-748
DOI:10.4103/1008-682X.155536  PMID:26067871
Cholesterol is a key molecule in the mammalian physiology of especial particular importance for the reproductive system as it is the common precursor for steroid hormone synthesis. Cholesterol is also a recognized modulator of sperm functions, not only at the level of gametogenesis. Cholesterol homeostasis regulation is crucial for posttesticular sperm maturation, and imbalanced cholesterol levels may particularly affect these posttesticular events. Metabolic lipid disorders (dyslipidemia) affect male fertility but are most of the time studied from the angle of endocrine/testicular consequences. This review will focus on the deleterious effects of a particular dyslipidemia, i.e., hypercholesterolemia, on posttesticular maturation of mammalian spermatozoa.
  6 4,383 522
The epididymis re-visited: a personal view
J Michael Bedford
September-October 2015, 17(5):693-698
DOI:10.4103/1008-682X.153297  PMID:25851661
  5 4,593 610
Sexual outcome of patients undergoing thulium laser enucleation of the prostate for benign prostatic hyperplasia
Luca Carmignani, Giorgio Bozzini, Alberto Macchi, Serena Maruccia, Stefano Picozzi, Stefano Casellato
September-October 2015, 17(5):802-806
DOI:10.4103/1008-682X.139255  PMID:25652616
Treatment of patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) may affect the quality of sexual function and ejaculation. The effect of new surgical procedures, which are currently available to treat BPH, on erection and ejaculation, has been poorly studied. This study aimed to assess the effect of thulium laser enucleation of the prostate (ThuLEP) on sexual function and retrograde ejaculation in patients with LUTS secondary to BPH. We performed a prospective study in 110 consecutive patients who had undergone ThuLEP to analyze changes in sexual function and urinary symptoms. To evaluate changes in erection and ejaculation, and the effect of urinary symptoms on the quality of life (QoL), five validated questionnaires were used: the ICIQ-MLUTSsex, MSHQ-EjD, International Index of Erectile Function 5, International Prognostic Scoring System (IPSS) questionnaire, and QoL index of the intraclass correlation coefficients. Patients also underwent IPSS and flowmetry to assess the outcome of flow. Patients were evaluated before surgery and 3-6 months after ThuLEP, whereas those with previous abdominal surgery were excluded. The patients' mean age was 67.83 years. Postoperative urinary symptoms improved after surgery. No significant differences in erectile function before and after surgery were observed. As compared with other techniques described in the literature, the percentage of patients with conserved ejaculation increased by 52.7% after ThuLEP. ThuLEP positively affects urinary symptoms and their effect on the QoL of patients as assessed by questionnaire scores. While endoscopic management of BPH (e.g. transurethral resection of the prostate) causes retrograde ejaculation in most patients, those who undergo ThuLEP have conserved ejaculation and erectile function.
  5 5,375 407
Role of Schwann cells in the regeneration of penile and peripheral nerves
Lin Wang, Melissa T Sanford, Zhongcheng Xin, Guiting Lin, Tom F Lue
September-October 2015, 17(5):776-782
DOI:10.4103/1008-682X.154306  PMID:25999359
Schwann cells (SCs) are the principal glia of the peripheral nervous system. The end point of SC development is the formation of myelinating and nonmyelinating cells which ensheath large and small diameter axons, respectively. They play an important role in axon regeneration after injury, including cavernous nerve injury that leads to erectile dysfunction (ED). Despite improvement in radical prostatectomy surgical techniques, many patients still suffer from ED postoperatively as surgical trauma causes traction injuries and local inflammatory changes in the neuronal microenvironment of the autonomic fibers innervating the penis resulting in pathophysiological alterations in the end organ. The aim of this review is to summarize contemporary evidence regarding: (1) the origin and development of SCs in the peripheral and penile nerve system; (2) Wallerian degeneration and SC plastic change following peripheral and penile nerve injury; (3) how SCs promote peripheral and penile nerve regeneration by secreting neurotrophic factors; (4) and strategies targeting SCs to accelerate peripheral nerve regeneration. We searched PubMed for articles related to these topics in both animal models and human research and found numerous studies suggesting that SCs could be a novel target for treatment of nerve injury-induced ED.
  5 9,032 590
Epididymal research: more warp than weft?
Trevor G Cooper
September-October 2015, 17(5):699-703
DOI:10.4103/1008-682X.146102  PMID:25652625
From a review of some aspects of epididymal structure, function and research done largely in my research area over the last 50 years, I conclude that more is known than is understood of sperm maturation and storage in the epididymis. Highly qualified technicians have not always applied sophisticated modern techniques in well-considered experiments to physiologically relevant and properly-prepared samples, so that our understanding of the biological problem of the nature of the epididymal epithelial influence on maturing epididymal spermatozoa has not kept pace with the outpouring of data generated, much of which is difficult to interpret. We stand at a crossroads of where to aim our limited resources and personnel: should we continue new technology-led studies in many directions, backtrack to test hypotheses and fill in gaps in our knowledge, or consider more biological directions to our research?
  4 4,112 547
Understanding normal and abnormal development of the Wolffian/epididymal duct by using transgenic mice
Aki Murashima, Bingfang Xu, Barry T Hinton
September-October 2015, 17(5):749-755
DOI:10.4103/1008-682X.155540  PMID:26112482
The development of the Wolffian/epididymal duct is crucial for proper function and, therefore, male fertility. The development of the epididymis is complex; the initial stages form as a transient embryonic kidney; then the mesonephros is formed, which in turn undergoes extensive morphogenesis under the influence of androgens and growth factors. Thus, understanding of its full development requires a wide and multidisciplinary view. This review focuses on mouse models that display abnormalities of the Wolffian duct and mesonephric development, the importance of these mouse models toward understanding male reproductive tract development, and how these models contribute to our understanding of clinical abnormalities in humans such as congenital anomalies of the kidney and urinary tract (CAKUT).
  4 4,664 538
Association between benign prostatic hyperplasia, body mass index, and metabolic syndrome in Chinese men
Zhuo Yin, Jin-Rui Yang, Jian-Ming Rao, Wei Song, Ke-Qin Zhou
September-October 2015, 17(5):826-830
DOI:10.4103/1008-682X.148081  PMID:25677137
Previous studies have showed that men suffering from diabetes mellitus, metabolic syndrome (MetS) and obesity have a higher risk of benign prostatic hyperplasia (BPH). The present study aimed to examine the association between BPH, obesity, and features of MetS among men of the Hunan area of China. For this cross-sectional study, 904 males (aged 50-59 years) were included. MetS parameters, International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA) levels, total prostate volume (TPV), postvoid residual volume (PVR) and maximum urine flow rate (Qmax) were measured. Results showed that MetS was associated with TPV (P = 0.048), PVR (P = 0.004) and IPSS (P = 0.011), but not with other indicators of BPH progression such as PSA levels or Qmax. MetS was associated with the voiding symptoms score (P < 0.05), but not with the storage symptom score. In addition, body mass index and fasting blood glucose positively correlated with TPV (r = 0.416, P< 0.001; and r = 0.310, P= 0.011, respectively). In conclusion, results suggest that MetS is associated with higher prostatic volume, prostate symptom score and voiding symptoms, but not with other features of prostatic hyperplasia such as PSA levels or Qmax. Changes in lifestyle factors, including physical activity and prevention of MetS, might be useful to prevent BPH and its progression, but further studies are needed.
  4 4,117 401
Re-epithelialization resulted from prostate basal cells in canine prostatic urethra may represent the ideal healing method after two-micron laser resection of the prostate
Ying Cao, Guang-Heng Luo, Lei Luo, Xiu-Shu Yang, Jian-Xin Hu, Hua Shi, Ping Huang, Zhao-Lin Sun, Shu-Jie Xia
September-October 2015, 17(5):831-838
DOI:10.4103/1008-682X.146972  PMID:25652631
The purpose of this study is to characterize the re-epithelialization of wound healing in canine prostatic urethra and to evaluate the effect of this re-epithelialization way after two-micron laser resection of the prostate (TmLRP). TmLRP and partial bladder neck mucosa were performed in 15 healthy adult male crossbred canines. Wound specimens were harvested at 3 days, and 1, 2, 3, and 4 weeks after operation, respectively. The histopathologic characteristics were observed by hematoxylin and eosin staining. The expression of cytokeratin 14 (CK14), CK5, CK18, synaptophysin (Syn), chromogranin A (CgA), uroplakin, transforming growth factor-β1 (TGF-β1 ), and TGF-β type II receptor in prostatic urethra wound were examined by immunohistochemistry and real-time polymerase chain reaction, respectively. Van Gieson staining was performed to determine the expression of collagen fibers in prostatic urethra and bladder neck would. The results showed that the re-epithelialization of the prostatic urethra resulted from the mobilization of proliferating epithelial cells from residual prostate tissue under the wound. The proliferating cells expressed CK14, CK5, but not CK18, Syn, and CgA and re-epithelialize expressed uroplakin since 3 weeks. There were enhanced TGF-β1 and TGF-β type II receptor expression in proliferating cells and regenerated cells, which correlated with specific phases of re-epithelialization. Compared with the re-epithelialization of the bladder neck, re-epithelialization of canine prostatic urethra was faster, and the expression of collagen fibers was relatively low. In conclusion, re-epithelialization in canine prostatic urethra resulted from prostate basal cells after TmLRP and this re-epithelialization way may represent the ideal healing method from anatomic repair to functional recovery after injury.
  3 3,954 326
Tetrandrine suppresses proliferation, induces apoptosis, and inhibits migration and invasion in human prostate cancer cells
Wei Liu, Bo Kou, Zhen-Kun Ma, Xiao-Shuang Tang, Chuan Lv, Min Ye, Jia-Qi Chen, Lei Li, Xin-Yang Wang, Da-Lin He
September-October 2015, 17(5):850-853
DOI:10.4103/1008-682X.142134  PMID:25677131
Tetrandrine (TET), a traditional Chinese medicine, exerts remarkable anticancer activity on various cancer cells. However, little is known about the effect of TET on human prostate cancer cells, and the mechanism of function of TET on prostate cancer has not yet been elucidated. To investigate the effects of TET on the suppression of proliferation, induction of apoptosis, and inhibition of migration and invasion in human prostate cancer cell lines, DU145 and PC-3. Inhibition of growth was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and clone formation assay, and flow cytometry analysis was performed to detect the induction of apoptosis. Activation of poly (ADP-ribose) polymerase, caspase-3, Akt, phospho-Akt, Bcl-2, and Bax was analyzed by Western blotting. Wound healing assay and transwell migration assay were used to evaluate the effect of TET on migration and invasion of cancer cells. TET inhibited the growth of DU145 and PC-3 cells in a dose- and time-dependent manner. Cell cloning was inhibited in the presence of TET in DU145 and PC-3 cells. TET suppressed the migration of DU145 and PC-3 cells. Transwell invasion assay showed that TET significantly weakened invasion capacity of DU145 and PC-3 cells. TET exhibited strong inhibitory effect on proliferation, migration, and invasion of prostate cancer cells. In addition, TET induced apoptosis in a dose-dependent manner by activating the caspase cascade and inhibiting phosphoinositide 3-kinase-Akt signal pathway. The accumulating evidence suggests that TET could be a potential therapeutic candidate against prostate cancer in a clinical setting.
  2 4,082 375
Gleason score and tumor laterality in radical prostatectomy and transrectal ultrasound-guided biopsy of the prostate: a comparative study
Renan A Pereira, Roberto S Costa, Valdair F Muglia, Fábio França Silva, Joyce S Lajes, Rodolfo B Dos Reis, Gyl EB Silva
September-October 2015, 17(5):815-820
DOI:10.4103/1008-682X.146970  PMID:25652629
We aimed to compare Gleason score and tumor laterality between transrectal ultrasound-guided biopsy of the prostate (TRUSBX) and radical prostatectomy (RP). Some factors that could cause a discrepancy in results between these two procedures were also evaluated. Among the 318 cases reviewed, 191 cases were selected for inclusion in this comparative study. We divided the patients into two groups using the Gleason score: an intermediate/high-grade group (≥7) and a low-grade group (<6). Exploratory analyses were conducted for comparisons between groups. We also performed comparisons between TRUSBX and RP for tumor laterality. TRUSBX overestimated 6% and underestimated 24% cases in comparison with RP for Gleason score, and overestimated 2.6% and underestimated 46% cases compared with RP for tumor laterality. Biopsy specimens were slightly smaller in TRUSBX cases with underestimated tumor laterality (P < 0.05), and no relationship between the biopsy specimen size and underestimated Gleason score in TRUSBX was found. Prostatic volume showed no statistical correlation with the likelihood of under or overestimation (P > 0.05). Thus, our study showed that TRUSBX has a high likelihood of underestimating both the Gleason score and tumor laterality in prostate cancer (PCa). The size of the fragment appears to be an important factor influencing the likelihood of laterality underestimation and Gleason score overestimation via TRUSBX. Due to the high likelihood of underestimation of the Gleason score and tumor laterality by 12-core prostate biopsy, we conclude that this type of biopsy should not be used alone to guide therapy in PCa.
  2 3,392 299
Prostate cancer detection upon transrectal ultrasound-guided biopsy in relation to digital rectal examination and prostate-specific antigen level: what to expect in the Chinese population?
Jeremy YC Teoh, Steffi KK Yuen, James HL Tsu, Charles KW Wong, Brian SH Ho, Ada TL Ng, Wai-Kit Ma, Kwan-Lun Ho, Ming-Kwong Yiu
September-October 2015, 17(5):821-825
DOI:10.4103/1008-682X.144945  PMID:25652619
We investigated the prostate cancer detection rates upon transrectal ultrasound (TRUS)-guided biopsy in relation to digital rectal examination (DRE) and prostate-specific antigen (PSA), and risk factors of prostate cancer detection in the Chinese population. Data from all consecutive Chinese men who underwent first TRUS-guided prostate biopsy from year 2000 to 2013 was retrieved from our database. The prostate cancer detection rates with reference to DRE finding and PSA level of < 4, 4-10, 10.1-20, 20.1-50 and > 50 ng ml−1 were investigated. Multivariate logistic regression analyses were performed to investigate for potential risk factors of prostate cancer detection. A total of 2606 Chinese men were included. In patients with normal DRE, the cancer detection rates were 8.6%, 13.4%, 21.8%, 41.7% and 85.2% in patients with PSA < 4, 4-10, 10.1-20, 20.1-50 and > 50 ng ml−1 respectively. In patients with abnormal DRE, the cancer detection rates were 12.4%, 30.2%, 52.7%, 80.6% and 96.4% in patients with PSA < 4, 4-10, 10.1-20, 20.1-50 and > 50 ng ml−1 respectively. Older age, smaller prostate volume, larger number of biopsy cores, presence of abnormal DRE finding and higher PSA level were associated with increased risk of prostate cancer detection upon multivariate logistic regression analyses (P < 0.001). Chinese men appeared to have lower prostate cancer detection rates when compared to the Western population. Taking the different risk factors into account, an individualized approach to the decision of TRUS-guided biopsy can be adopted.
  2 3,465 359
Phosphorylation of Izumo1 and Its Role in Male Infertility
Samantha A. M. Young, John Aitken, Mark A. Baker
September-October 2015, 17(5):708-710
DOI:10.4103/1008-682X.156119  PMID:25994654
Izumo1 is a testis-specific gene product, whose function is essential for sperm-egg fusion. Throughout its lifespan, Izumo1 is posttranslationally modified, being both N-linked glycosylated on its extracellular domain and phosphorylated on the intracellular C-terminal tail. Within the caput regions of the rat epididymis, two phosphorylation events have been documented. However, as sperm pass through the epididymis, this cytoplasmic portion of Izumo1 has been shown to contain up to seven phosphorylation sites. Remarkably, in the rat, in correlation with these events, Izumo1 undergoes sub-cellular re-location, moving from the head/tail regions of the spermatozoa, to a predominantly equatorial segment location once they have reached the caudal end of the epididymis.
  1 4,597 540
The role of Dicer1 in the male reproductive tract
Ida Björkgren, Petra Sipilä
September-October 2015, 17(5):737-741
DOI:10.4103/1008-682X.155542  PMID:25994652
Dicer1 is an RNase III enzyme necessary for microRNA (miRNA) biogenesis, as it cleaves pre-miRNAs into mature miRNAs. miRNAs are important regulators of gene expression. In recent years, several miRNA-independent roles of Dicer1 have been identified. They include the production of endogenous small interfering RNAs, detoxifying retrotransposon-derived transcripts, and binding to new targets; messenger RNAs and long noncoding RNAs. Further, in this review, the functional significance of Dicer1 in the male reproductive tract is discussed. Conditional Dicer1 knock-out mouse models have demonstrated a requisite role for Dicer in male fertility. Deletion of Dicer1 from somatic or germ cells in the testis cause spermatogenic problems rendering male mice infertile. The lack of Dicer1 in the proximal epididymis causes dedifferentiation of the epithelium, with unbalanced sex steroid receptor expression, defects in epithelial lipid homeostasis, and subsequent male infertility. In addition, Dicer1 ablation from the prostate leads to increased apoptosis of the differentiated luminal cells, followed by epithelial hypotrophy of the ventral prostate. However, further studies are needed to clarify which functions of Dicer1 are responsible for the observed phenotypes in the male reproductive tract.
  1 2,592 241
Upgrading and upstaging of low-risk prostate cancer among Korean patients: a multicenter study
Insang Hwang, Donghoon Lim, Young Beom Jeong, Seung Chol Park, Jun Hwa Noh, Dong Deuk Kwon, Taek Won Kang
September-October 2015, 17(5):811-814
DOI:10.4103/1008-682X.143751  PMID:25578934
Only 54% of prostate cancer cases in Korea are localized compared with 82% of cases in the US. Furthermore, half of Korean patients are upgraded after radical prostatectomy (41.6%-50.6%). We investigated the risk factors for upgrading and/or upstaging of low-risk prostate cancer after radical prostatectomy. We retrospectively reviewed the medical records of 1159 patients who underwent radical prostatectomy at five hospitals in Honam Province. Preoperative data on standard clinicopathological parameters were collected. The radical prostatectomy specimens were graded and staged and we defined a "worsening prognosis" as a Gleason score ≥ 7 or upstaging to ≥ pT3. Multivariate logistic regression models were used to assess factors associated with postoperative pathological upstaging. Among the 1159 patients, 324 were classified into the clinically low-risk group, and 154 (47.5%) patients were either upgraded or upstaged. The multivariable analysis revealed that the preoperative serum prostate-specific antigen level (odds ratio [OR], 1.131; 95% confidence interval [CI], 1.007-1.271; P= 0.037), percent positive biopsy core (OR: 1.018; 95% CI: 1.002-1.035; P= 0.032), and small prostate volume (≤30 ml) (OR: 2.280; 95% CI: 1.351-3.848; P= 0.002) were predictive of a worsening prognosis. Overall, 47.5% of patients with low-risk disease were upstaged postoperatively. The current risk stratification criteria may be too relaxed for our study cohort.
  1 3,296 265
Management of end-stage erectile dysfunction and stress urinary incontinence after radical prostatectomy by simultaneous dual implantation using a single trans-scrotal incision: surgical technique and outcomes
Juan I Martinez-Salamanca, Estefanía Linares Espinós, Ignacio Moncada, Luis Del Portillo, Joaquín Carballido
September-October 2015, 17(5):792-796
DOI:10.4103/1008-682X.143757  PMID:25657083
Stress urinary incontinence (SUI) and end-stage erectile dysfunction (ED) after radical prostatectomy (RP) can decrease a patient's quality of life (QoL). We describe a surgical technique involving scrotal incision for simultaneous dual implantation of an artificial urinary sphincter (AUS) and an inflatable penile prosthesis (IPP). Patients with moderate to severe SUI (>3 pads per day) and end-stage ED following RP were selected for dual implantation. An upper transverse scrotal incision was made, followed by bulbar urethra dissection and AUS cuff placement. Through the same incision, the corpora cavernosa was exposed, and an IPP positioned. Followed by extraperitoneal reservoirs placement and pumps introduced in the scrotum. Short-term, intra- and post-operative complications; continence status and erectile function; and patient satisfaction and QoL were recorded. A total of 32 patients underwent dual implantation. Early AUS-related complications were: AUS reservoir migration and urethral erosion. One case of distal corporal extrusion occurred. No prosthetic infection was reported. Over 96% of patients were socially the continent (≤1 pad per day) and > 95% had sufficient erections for intercourse. Limitations of the study were the small number of patients, the lack of the control group using a perineal approach for AUS placement and only a 12 months follow-up. IPP and AUS dual implantation using a single scrotal incision technique is a safe and effective option in patients with SUI and ED after RP. Further studies on larger numbers of patients are warranted.
  1 4,126 263
Chronic administration of sildenafil improves erectile function in a rat model of chronic renal failure
Nilgun Gurbuz, Arif Kol, Tumay Ipekci, Erhan Ates, Asli Baykal, Mustafa F Usta
September-October 2015, 17(5):797-801
DOI:10.4103/1008-682X.146973  PMID:25652632
The relationship between erectile dysfunction (ED) and chronic renal failure (CRF) has been reported in several studies. This study aimed to investigate whether the chronic use of sildenafil could enhance the erectile capacity in CRF-induced rats. In addition, we assessed the effect of that treatment on certain molecules, which have been suggested to play crucial roles in erectile physiology and CRF-related ED as well. Three groups of animals were utilized: (1) age-matched control rats, (2) CRF-induced rats, (3) CRF-induced rats treated with chronic administration of sildenafil (5 mg kg−1 p.o. for 6 weeks [treatment started after 6 weeks of CRF induction]). At 3 months, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Penile tissue advanced glycation end products (AGE's)/5-hydroxymethyl-2-furaldehyde, malondialdehyde (MDA), cGMP (ELISA), inducible nitric oxide synthase (iNOS) and neuronal NOS (nNOS) (Western blot) analyses were performed in all rat groups. CRF-induced rats had a significant decrease in erectile function when compared to control rats (P < 0.05). The increase in both intracavernosal pressure (ICP) and area under the curve of CRF-induced rats treated with sildenafil (Group 3) was greater than CRF-induced rats (Group 2). Additionally, sildenafil treatment decreased AGE, MDA and iNOS levels, while it preserved nNOS and cGMP contents in CRF-induced penile tissue. Decreased AGE, MDA, iNOS and increased nNOS, cGMP levels at the sildenafil-treated group increased both ICP and Total ICP to CNS, which led to improve erectile function in CRF-induced rats. The results of the present study revealed the therapeutic effect of chronic sildenafil administration on erectile function in CRF-induced rats.
  1 3,575 356
ICSI treatment of severe male infertility can achieve prospective embryo quality compared with IVF of fertile donor sperm on sibling oocytes
Ju-Fen Zheng, Xiao-Bao Chen, Lei-Wen Zhao, Min-Zhi Gao, Jie Peng, Xian-Qin Qu, Hui-Juan Shi, Xing-Liang Jin
September-October 2015, 17(5):845-849
DOI:10.4103/1008-682X.146971  PMID:25652630
Azoospermia, cryptozoospermia and necrospermia can markedly decrease the ability of males to achieve pregnancy in fertile females. However, patients with these severe conditions still have the option to be treated by intracytoplasmic sperm injection (ICSI) to become biological fathers. This study analyzed the fertilization ability and the developmental viabilities of the derived embryos after ICSI treatment of the sperm from these patients compared with in vitro fertilization (IVF) treatment of the proven-fertile donor sperm on sibling oocytes as a control. On the day of oocyte retrieval, the number of sperm suitable for ICSI collected from two ejaculates or testicular sperm extraction was lower than the oocytes, and therefore, excess sibling oocytes were treated by IVF with donor sperm. From 72 couples (73 cycles), 1117 metaphase II oocytes were divided into 512 for ICSI and 605 for IVF. Compared with the control, husbands' sperm produced a lower fertilization rate in nonobstructive azoospermia (65.4% vs 83.2%; P< 0.001), crytozoospermia (68.8% vs 75.5%; P< 0.05) and necrospermia (65.0% vs 85.2%; P< 0.05). The zygotes derived in nonobstructive azoospermia had a lower cleavage rate (96.4% vs 99.4%; P< 0.05), but the rate of resultant good-quality embryos was not different. Analysis of the rates of cleaved and good-quality embryos in crytozoospermia and necrospermia did not exhibit a significant difference from the control. In conclusion, although the sperm from severe male infertility reduced the fertilization ability, the derived embryos had potential developmental viabilities that might be predictive for the expected clinical outcomes.
  1 3,764 389
Exploring the epididymis: a personal perspective on careers in science
Terry T Turner
September-October 2015, 17(5):704-707
DOI:10.4103/1008-682X.145432  PMID:25578939
Science is a profession of inquiry. We ask ourselves what is it we see and why our observations happen the way they do. Answering those two question puts us in the company of those early explorers, who from Europe found the New World, and from Asia reached west to encounter Europe. Vasco Núñez de Balboa of Spain was such an explorer. He was the first European to see or "discover" the Pacific Ocean. One can imagine his amazement, his excitement when he first saw from a mountain top that vast ocean previously unknown to his culture. A career in science sends each of us seeking our own "Balboa Moments," those observations or results that surprise or even amaze us, those discoveries that open our eyes to new views of nature and medicine. Scientists aim to do what those early explorers did: discover what has previously been unknown, see what has previously been unseen, and reveal what has previously been hidden. Science requires the scientist to discover the facts from among many fictions and to separate the important facts from the trivial so that knowledge can be properly developed. It is only with knowledge that old dogmas can be challenged and corrected. Careers in science produce specific sets of knowledge. When pooled with other knowledge sets they eventually contribute to wisdom and it is wisdom, we hope, that will improve the human condition.
  - 3,278 424
Looking both ways: new research on old theories
Trevor G Cooper
September-October 2015, 17(5):764-766
DOI:10.4103/1008-682X.160265  PMID:26208399
  - 2,266 306
Epididymal research one generation on
Yongliang Zhang, Trevor G Cooper
September-October 2015, 17(5):691-692
DOI:10.4103/1008-682X.160264  PMID:26208398
  - 3,283 466
Novel phenotype of mouse spermatozoa following deletion of nine β-defensin genes
Julia R Dorin
September-October 2015, 17(5):716-719
DOI:10.4103/1008-682X.159712  PMID:26262774
β-defensin peptides are a large family of antimicrobial peptides. Although they kill microbes in vitro and interact with immune cells, the precise role of these genes in vivo remains uncertain. Despite their inducible presence at mucosal surfaces, their main site of expression is the epididymis. Recent evidence suggests that a major function of these peptides is in sperm maturation. In addition to previous work suggesting this, work at the MRC Human Genetics Unit, Edinburgh, has shown that homozygous deletion of a cluster of nine β-defensin genes in the mouse results in profound male sterility. The spermatozoa derived from the mutants had reduced motility and increased fragility. Epididymal spermatozoa isolated from the cauda region of the homozygous mutants demonstrated precocious capacitation and increased spontaneous acrosome reactions compared with those from wild-types. Despite this, these mutant spermatozoa had reduced ability to bind to the zona pellucida of oocytes. Ultrastructural examination revealed a disintegration of the microtubule structure of mutant-derived spermatozoa isolated from the epididymal cauda region, but not from the caput. Consistent with premature acrosome reaction and hyperactivation, spermatozoa from mutant animals had significantly increased intracellular calcium content. This work demonstrates that in vivo β-defensins are essential for successful sperm maturation, and that their disruption alters intracellular calcium levels, which most likely leads to premature activation and spontaneous acrosome reactions that result in hyperactivation and loss of microtubule structure of the axoneme. Determining which of the nine genes are responsible for the phenotype and the relevance to human sperm function is important for future work on male infertility.
  - 3,285 437
Commentary on - "Comparison of the efficacy and safety of once-daily dosing and on-demand use of udenafil for type 2 diabetic patients with erectile dysfunction"
De-Hong Cao, Liang-Ren Liu, Qiang Wei
September-October 2015, 17(5):854-854
DOI:10.4103/1008-682X.148069  PMID:25652635
  - 2,338 243
Mother and daughter became father and son: a case report
Tatjana Sajevets, Charlotte Verroken, Gunter Heylens, Elfride De Baere, Guy T'Sjoen
September-October 2015, 17(5):855-856
DOI:10.4103/1008-682X.145430  PMID:25652622
  - 3,442 324
An insertion mutation in the androgen receptor gene in a patient with azoospermia
Yun-Hao Chen, Hui-Ying Xu, Zhang-Yang Wang, Zhe-Hui Zhu, Cheng-Di Li, Zhi-Gang Wu, Bi-Cheng Chen
September-October 2015, 17(5):857-858
DOI:10.4103/1008-682X.148724  PMID:25677139
  - 2,562 325
Glutathione S-transferase T1: a potential marker for the selection of varicocelectomy in infertile male patients with varicocele
Qi-Fei Wu, Kai-Fa Tang, Jian-Hua Sun, Jun-Ping Xing
September-October 2015, 17(5):859-860
DOI:10.4103/1008-682X.149179  PMID:25677140
  - 2,381 282
The association between metabolic syndrome and advanced prostate cancer in Chinese patients receiving radical prostatectomy
Gui-Ming Zhang, Yao Zhu, Da-Hai Dong, Cheng-Tao Han, Cheng-Yuan Gu, Wei-Jie Gu, Xiao-Jian Qin, Li-Jiang Sun, Ding-Wei Ye
September-October 2015, 17(5):839-844
DOI:10.4103/1008-682X.148138  PMID:25652638
The global incidence of metabolic syndrome (MetS) is dramatically increasing. Considerable interest has been devoted to the relationship between MetS and prostate cancer (PCa) risk. However, few studies have examined the association between MetS and PCa progression. This retrospective study consisted of 1016 patients with PCa who received radical prostatectomy. The association between MetS and pathological features was evaluated using logistic regression analysis. Compared with patients without MetS, those with MetS indicated an increased risk of prostatectomy Gleason score (GS) ≥8 (odds ratio [OR] =1.670, 95% confidence interval (CI) 1.096-2.545, P= 0.017), and a 1.5-fold increased risk of pT3-4 disease (OR = 1.583, 95% CI 1.106-2.266, P= 0.012). The presence of MetS was an independent predictor of lymph node involvement (OR = 1.751, 95% CI 1.038-2.955, P= 0.036). Furthermore, as the number of MetS components accumulated, the risk of a GS ≥ 8 increased. The present study indicates a significant association between MetS and advanced PCa. The results need to be evaluated in large-scale prospective cohorts.
  - 2,315 297
Combined tests of prostate specific antigen and testosterone will improve diagnosis and monitoring the progression of prostate cancer
Weitao Song, Vikram Soni, Mohit Khera
September-October 2015, 17(5):807-810
DOI:10.4103/1008-682X.148721  PMID:25761834
Prostate-specific antigen (PSA) testing has been widely used to screen men for prostate cancer (PCa) and to monitor PCa progression. However, more studies have shown that around 15% of men with low or normal PSA levels have PCa. In this study, we aimed to investigate the relationship of androgen and PSA levels and to better understand the reason that some PCa patients have low serum PSA values. The in vitro data demonstrated that cultured LNCaP cells ceased to produce PSA after androgen withdrawal and resumed PSA production after androgen was re-added. The in vivo experiment results showed that 48% of PCa xenografts carrying mice have serum PSA level lower than 4 ng ml−1 . The serum PSA levels increased significantly with rises in testosterone (T) levels 1 week after T pellet implantation. These data indicated that the androgen is a key factor controlling the production of PSA. Low serum PSA levels in mice with PCa xenografts are associated with low serum T levels. Raising serum T levels in tumor caring mice will also significantly increase serum PSA level. This may have clinical implications when screening PSA in men, who have occult PCa.
  - 3,267 324
From bench to bedside: bipolar androgen therapy in a pilot clinical study
Qing Zhang, Phillip J Gray
September-October 2015, 17(5):767-768
DOI:10.4103/1008-682X.151390  PMID:25814159
Prostate cancer remains a leading cause of cancer death in Europe and the United States and is an emerging problem in Asia despite significant improvements in available treatments over the last few decades. Androgen deprivation therapy (ADT) has been the core treatment of advance-staged disease since the discovery of prostate cancer's androgen dependence in 1941 by Huggins et al. [1] Options for initial medical treatment include gonadotropin-releasing hormone analogues such as leuprolide (LHRH agonist) and degarelix (LHRH antagonist) and androgen receptor (AR) binding agents such as bicalutamide. Although most patients will initially respond to either surgical or medical castration, there is almost always progression to castration-resistant prostate cancer (CRPC) necessitating treatment with more novel agents. [2] However, even drugs such as abiraterone and enzalutamide, two next-generation agents used commonly in metastatic CRPC, have failed to demonstrate persistent efficacy in most patients. [3] ,[4]
  - 3,366 317
Locally-advanced prostate cancer in the elderly: should we revisit our treatment paradigms?
Giovanni Lughezzani, Nicoló Maria Buffi
September-October 2015, 17(5):769-770
DOI:10.4103/1008-682X.151394  PMID:25926604
Prostate cancer (PCa) represents the most common malignancy in adult males with an estimated number of 280 000 newly diagnosed cases only in the United States in 2015. [1] Due to the introduction of PSA in clinical practice, the majority of the patients are currently diagnosed with organ-confined and sometimes indolent disease. However, a nonnegligible proportion of individuals are still diagnosed with locally-advanced tumors. In their recently published article, Bekelman et al. [2] focused on elderly patients with locally-advanced PCa in the attempt to determine the best treatment approach in this patient category, and concluded that, even in these individuals, androgen deprivation therapy (ADT) plus radiotherapy (RT) may confer a survival benefit relative to ADT alone. The importance of the current article resides in the fact that it focuses on a patient population that has not been, or has been only scarcely, included in previous studies on the same topic.
  - 2,487 227
Heart healthy equals prostate healthy and statins, aspirin, and/or metformin (S.A.M.) are the ideal recommendations for prostate cancer prevention
Mark A Moyad, Nicholas J Vogelzang
September-October 2015, 17(5):783-791
DOI:10.4103/1008-682X.148070  PMID:25657084
Cardiovascular disease (CVD) has been the number one cause of death in the U.S. for 114 of the last 115 years. Lifestyle factors that promote CVD also appear to increase prostate cancer risk and those that reduce CVD risk also appear to reduce the risk of prostate cancer. The largest randomized trials utilizing dietary supplements or pharmacologic agents for prostate cancer prevention (Selenium and Vitamin E Cancer Prevention Trial [SELECT]) have also shed light on the problems and future solutions in this area. Dietary supplements that have not been found to be CVD protective, such as selenium and Vitamin E have not been found to be prostate protective. In addition, over exposure to specific anti-oxidants in nutritionally replete populations may be encouraging cancer growth. Future trials of dietary supplements to prevent prostate cancer could be problematic because by the time a definitive trial is initiated the participants will no longer be "deficient" in the nutrient being tested, which arguably occurred in the SELECT trial. It is also interesting that statins, aspirin, and/or metformin (S.A.M.) are 3 generic, low-cost, heart healthy agents derived from natural sources with separate mechanism of actions, which all appear to have the best benefit to risk ratio compared to any other agent available for prostate cancer prevention, especially aggressive disease, or as an ancillary agent (s) to conventional cancer treatment. It is time to focus on the forest over the trees and recommend proven CVD protective measures for men concerned about their risk of prostate cancer.
  - 5,250 368