Journal Of Andrology[JOURNAL]
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200 papers
Glutathione peroxidases at work on epididymal spermatozoa: an example of the dual effect of reactive oxygen species on mammalian male fertilizing ability.
Noblanc A, Kocer A, Chabory E … +5 more , Vernet P, Saez F, Cadet R, Conrad M, Drevet JR
J Androl · 2011 · PMID 21441427 · Publisher ↗
The mammalian glutathione peroxidase (GPx) gene family encodes bifunctional enzymes that can work either as classical reactive oxygen species (ROS) scavengers or as thiol peroxidases, thereby introducing disulfide bridge...
The mammalian glutathione peroxidase (GPx) gene family encodes bifunctional enzymes that can work either as classical reactive oxygen species (ROS) scavengers or as thiol peroxidases, thereby introducing disulfide bridges in thiol-containing proteins. These dual effects are nowhere better demonstrated than in epididymal maturing spermatozoa, where the concomitant actions of several GPx ensure the achievement of the structural maturation of sperm cells as well as their protection against ROS-induced damage. We review here the roles played by the sperm-associated forms of GPx4 (mitochondrial GPx4 and nuclear GPx4), the secreted GPx5 protein, and the epithelial proteins GPx1, GPx3, and cellular GPx4, all functioning in the mammalian epididymis at different stages of the sperm's epididymal journey, and in different epididymis compartments.
Thirsty business: cell, region, and membrane specificity of aquaporins in the testis, efferent ducts, and epididymis and factors regulating their expression.
Hermo L, Smith CE
J Androl · 2011 · PMID 21441426 · Publisher ↗
Water content within the male reproductive tract is stringently regulated in order to promote sperm differentiation and maturation. Aquaporins (AQP) are a family of integral membrane proteins allowing the transcellular t...
Water content within the male reproductive tract is stringently regulated in order to promote sperm differentiation and maturation. Aquaporins (AQP) are a family of integral membrane proteins allowing the transcellular transport of water, gases, urea, glycerol, and ions. Past studies from our lab have revealed the following. In the testis, Sertoli cells express AQP 8, whereas germ cells express AQP 7. In the efferent ducts (ED), AQP 1, 9, and 10 localize to microvilli of nonciliated cells, in addition to a basolateral staining for AQP 1, whereas AQP 1 and 10 localize to ciliated cells. AQP 7 and 11 are expressed in the ED epithelium of young but not adult rats, suggesting suppression of translation as rats age. In the adult epididymis, AQP 1 appears in endothelial cells of vascular channels and myoid cells, whereas AQP 3 delineates basal cells. In principal cells, AQP 9 and 11 appear on microvilli, whereas AQP 7 localizes to lateral then to basal plasma membranes in a region-specific manner; AQP 7 also associates with myoid cells. AQP 5 is expressed in corpus and cauda regions. Additionally, several AQPs are expressed by some but not all basal (AQP 7, 11), clear (AQP 7, 9), and halo (AQP 7, 11) cells. Regulation studies reveal a role for estrogen, androgens, and lumicrine factors. These findings indicate unique associations of AQPs with specific membrane domains in a cell type- and region-specific manner within the EDs and epididymis, as well as complex regulation patterns of expression.
Estrogen and its receptors in efferent ductules and epididymis.
Hess RA, Fernandes SA, Gomes GR … +3 more , Oliveira CA, Lazari MF, Porto CS
J Androl · 2011 · PMID 21441425 · Publisher ↗
Estrogens play key roles in the development and maintenance of male reproductive function and fertility. In this review, we briefly describe the localization and function of estrogen receptors ESR1 and ESR2 (also known a...
Estrogens play key roles in the development and maintenance of male reproductive function and fertility. In this review, we briefly describe the localization and function of estrogen receptors ESR1 and ESR2 (also known as ERα and ERβ, respectively) and the expression of G protein-coupled estrogen receptor-1 (GPER, formerly known as GPR30) in efferent ductules and epididymis. The efferent ductules present the highest levels of ESR1 and ESR2 in the male reproductive system, and represent a major target of estrogen action. In efferent ductules, ESR1 has a crucial role in the regulation of fluid reabsorption, and in the epididymis the receptor helps to maintain fluid osmolality and pH. ESR1 expression in the epididymal epithelium shows considerable variation among species, but differences in laboratory techniques may also contribute to this variation. Here we report that Esr1 mRNA and protein are higher in corpus than in other regions of the rat epididymis. The mRNA level for Gper was also higher in corpus. Although ESR1 is expressed constitutively in efferent ductules and down-regulated by estrogen, in the epididymis, both testosterone (T) and estradiol (E2) may regulate its expression. T and E2 are, respectively, higher and lower in the corpus than in the initial segment/caput and cauda regions. It is important to determine the expression of GPER, ESR1, androgen receptor, and their respective cofactors in specific cell types of this tissue, as well as the intracellular signaling pathways involved in efferent ductules and epididymis. These studies will help to explain the consequences of exposures to environmental endocrine disruptors and provide potential targets for the development of a male contraceptive.
Epididymal protein CRISP1 plays different roles during the fertilization process.
Cohen DJ, Maldera JA, Vasen G … +4 more , Ernesto JI, Muñoz MW, Battistone MA, Cuasnicú PS
J Androl · 2011 · PMID 21441424 · Publisher ↗
Rat epididymal CRISP1, the first described member of the evolutionarily conserved Cysteine-RIch Secretory Protein (CRISP) family, is expressed in the proximal regions of the epididymis and associates with the sperm durin...
Rat epididymal CRISP1, the first described member of the evolutionarily conserved Cysteine-RIch Secretory Protein (CRISP) family, is expressed in the proximal regions of the epididymis and associates with the sperm during epididymal transit. Evidence indicates the existence of 2 populations of CRISP1 in spermatozoa: a major one, loosely bound, which is released during capacitation and, therefore, proposed as a decapacitating factor; and a minor one, strongly associated with spermatozoa that remains on the cells after capacitation and is proposed to participate in gamete interaction. Originally localized to the dorsal region of capacitated sperm, CRISP1 migrates to the equatorial segment with capacitation and acrosome reaction. Consistent with these localizations, in vitro fertilization experiments support the involvement of CRISP1 in the first step of sperm-zona pellucida (ZP) interaction and subsequent gamete fusion through its interaction with egg-complementary sites. The potential roles of CRISP1 in capacitation and fertilization have been further supported by the finding that capacitated spermatozoa from CRISP1 "knockout" animals exhibit low levels of protein tyrosine phosphorylation and have an impaired ability to fertilize zona-intact and zona-free eggs in vitro. Moreover, recent evidence from mutant spermatozoa reveals that CRISP1 mediates the stage of sperm binding to the ZP. Altogether, these observations support the view that CRISP1 is a multifunctional protein playing different roles during fertilization through its different associations with and localizations on spermatozoa. We believe these results contribute to a better understanding of the molecular mechanisms involved in both the fertilization process and the acquisition of sperm-fertilizing ability that occurs during epididymal maturation.
Establishment of cell-cell cross talk in the epididymis: control of luminal acidification.
Shum WW, Ruan YC, Da Silva N … +1 more , Breton S
J Androl · 2011 · PMID 21441423 · Full text
Male infertility is often caused by sperm that have low motility and interact poorly with the oocyte. Spermatozoa acquire these crucial functions in the epididymis. A low luminal bicarbonate (HCO(3)(-)) concentration and...
Male infertility is often caused by sperm that have low motility and interact poorly with the oocyte. Spermatozoa acquire these crucial functions in the epididymis. A low luminal bicarbonate (HCO(3)(-)) concentration and low pH keep sperm quiescent during their maturation and storage in this organ. This review describes how epididymal epithelial cells work in a concerted manner, together with spermatozoa, to establish and maintain this acidic luminal environment. Clear cells express the proton-pumping ATPase (V-ATPase) in their apical membrane and actively secrete protons. HCO(3)(-) induces V-ATPase accumulation in apical microvilli in clear cells via HCO(3)(-)-sensitive adenylyl cyclase-dependent cAMP production. HCO(3)(-) is secreted from principal cells following basolateral stimulation, to transiently "prime" spermatozoa before ejaculation. Luminal ATP and adenosine also induce V-ATPase apical accumulation in clear cells via activation of P2 and P1 receptors, respectively. ATP is released into the lumen from sperm and principal cells and is then metabolized into adenosine by local nucleotidases. In addition, the V-ATPase is regulated by luminal angiotensin II via activation of basal cells, which can extend narrow body projections that cross the tight junction barrier. Basal cells then secrete nitric oxide, which diffuses out to stimulate proton secretion in clear cells via activation of the cGMP pathway. Thus, an elaborate communication network is present between principal cells and clear cells, and between basal cells and clear cells, to control luminal acidification. Monitoring and decoding these "intercellular conversations" will help define pathophysiologic mechanisms underlying male infertility.
Looking to the future of epididymal research: why this, why now?
Turner TT
J Androl · 2011 · PMID 21441422 · Publisher ↗
Epididymal biology is an area of science at risk. Never a large field to begin with (the number of papers produced by laboratories studying the epididymis is roughly only 20% of the number produced by laboratories studyi...
Epididymal biology is an area of science at risk. Never a large field to begin with (the number of papers produced by laboratories studying the epididymis is roughly only 20% of the number produced by laboratories studying the testis), it tends to shrink even further in times of funding crisis. This matters because the numbers of laboratories, investigators, and trainees in any area of science affects the number of new people coming into the field, the new ideas that new people can bring, and the number of interested scientists on important grant review panels. How can epididymal biologists face the current challenges? First, great ideas are the key. They prompt compelling hypotheses that can be challenged with interesting experiments. Second, it must be recognized that the past is past. The fact that studies on sperm maturation, epididymal histology, or tubule physiology are significant parts of the past does not mean that they are no longer interesting, but it does mean that truly original questions in those areas will likely be difficult to find. In the real world of competitive science, national granting agencies require applications that clearly answer the questions, why is this of interest and why is it important now? Productive areas of future research may include lumicrine regulation of the epithelium, immunobiology of the epididymis, and cell-cell communication between epididymal epithelial cells and cells in the peritubular/interstitial space.
How do you get six meters of epididymis inside a human scrotum?
Hinton BT, Galdamez MM, Sutherland A … +4 more , Bomgardner D, Xu B, Abdel-Fattah R, Yang L
J Androl · 2011 · PMID 21441421 · Publisher ↗
It is very clear that the epididymis plays a crucial role in the maturation of spermatozoa, and without a fully developed and functional epididymis, male infertility will result. We are especially interested in understan...
It is very clear that the epididymis plays a crucial role in the maturation of spermatozoa, and without a fully developed and functional epididymis, male infertility will result. We are especially interested in understanding the mechanisms that regulate the development of this important organ because disruptions to epididymal function will also arise as a consequence of abnormal development. Very little is known either of the process of epididymal development or the nature and causes of congenital defects that lead to male infertility. A major event during Wolffian/epididymal duct embryonic development is elongation and coiling and this short review outlines potential mechanisms by which these events occur. It is hypothesized that elongation is the result of cell proliferation coupled with directed cell rearrangements, the later regulated by the planar cell polarity signaling pathway. Coiling proceeds in a proximal to distal manner, with three-dimensional coiling beginning approximately embryonic day 16.5 to 18.5 in the mouse. The exact mechanisms of coiling are not known but we hypothesize that it involves an interaction between the Wolffian duct epithelium and the surrounding mesenchyme cells, such that the extracellular matrix is remodeled to allow coiling and growth of the duct. Cell proliferation in the Wolffian duct appears to be dependent on the presence of androgens and mesenchymal factors during embryonic development, but lumicrine factors play an additional role during postnatal development.
A novel treatment of chronic orchialgia.
Basal S, Ergin A, Yildirim I … +6 more , Goktas S, Atim A, Sizlan A, Irkilata HC, Kurt E, Dayanc M
J Androl · 2012 · PMID 21436311 · Publisher ↗
We evaluated the effectiveness of pulsed radiofrequency (PRF) denervation of spermatic cord for the treatment of chronic orchialgia. Five patients diagnosed with chronic orchialgia were evaluated with a thorough medical...
We evaluated the effectiveness of pulsed radiofrequency (PRF) denervation of spermatic cord for the treatment of chronic orchialgia. Five patients diagnosed with chronic orchialgia were evaluated with a thorough medical and psychiatric history, physical examination, and scrotal Doppler ultrasound, urinary system x-ray film, and urine analyses. One of the patients had bilateral chronic orchialgia. All of the patients had pain for a period of at least 3 months, and multiple conservative therapies failed to alleviate the pain. The patients, who had temporary pain relief after undergoing outpatient diagnostic cord block, were determined to be candidates for PRF denervation. PRF denervation of spermatic cord was performed for 6 testicular units. Visual analog scores were noted before and after the procedure. There were no pathologic conditions that indicated chronic orchialgia in any of the patients. No complications, including testicular atrophy or hypoesthesia of the scrotal or penile skin, occurred after the procedure. Mean visual analog scores before and after the procedure were 9 and 1, respectively. None of the patients needed any analgesics after the procedure or during the follow-up period. Mean follow-up period was 20 ± 2.5 weeks. No recurrence was noted, and none of the patients needed additional therapy. This is a limited case report on the short-term use of PRF. Randomized, placebo-controlled, and long follow-up period studies are needed to better assess the efficacy of this procedure for chronic orchalgia.
The mitochondria of stallion spermatozoa are more sensitive than the plasmalemma to osmotic-induced stress: role of c-Jun N-terminal kinase (JNK) pathway.
García BM, Moran AM, Fernández LG … +7 more , Ferrusola CO, Rodriguez AM, Bolaños JM, da Silva CM, Martínez HR, Tapia JA, Peña FJ
J Androl · 2012 · PMID 21436310 · Publisher ↗
Cryopreservation introduces extreme temperature and osmolality changes that impart lethal and sublethal effects on spermatozoa. Additionally, there is evidence that the osmotic stress induced by cryopreservation causes o...
Cryopreservation introduces extreme temperature and osmolality changes that impart lethal and sublethal effects on spermatozoa. Additionally, there is evidence that the osmotic stress induced by cryopreservation causes oxidative stress to spermatozoa. The main sources of reactive oxygen species in mammalian sperm are the mitochondria. In view of this, the aim of our study was to test whether or not osmotic stress was able to induce mitochondrial damage and to explore the osmotic tolerance of the mitochondria of stallion spermatozoa. Ejaculates from 7 stallions were subjected to osmolalities ranging from 75 to 1500 mOsm/kg, and the effect on sperm membrane integrity and mitochondrial membrane potential was studied. Additionally, the effects of changes in osmolality from hyposmotic to isosmotic and from hyperosmotic to isosmotic solutions were studied (osmotic excursions). The cellular volume of stallion spermatozoa under isosmotic conditions was 20.4 ± 0.33 μm(3). When exposed to low osmolality, the stallion spermatozoa behaved like a linear osmometer, whereas exposure to high osmolalities up to 900 mOsm/kg resulted in decreased sperm volume. Although sperm membranes were relatively resistant to changes in osmolality, mitochondrial membrane potential decreased when osmolalities were low or very high (10.7 ± 1.74 and 16.5 ± 1.70 at 75 and 150 mOsm/kg, respectively, and 13.1 ± 1.83 at 1500 mOsm/kg), whereas in isosmolar controls the percentage of stallion sperm mitochondria with a high membrane potential was 41.1 ± 1.69 (P < .01). Osmotic excursions induced greater damage than exposure of spermatozoa to a given nonphysiologic osmolality, and again the mitochondria were more prone to damage induced by osmotic excursions than was the sperm plasma membrane. In search of intracellular components that could mediate these changes, we have detected for the first time the c-Jun N-terminal kinase 1/2 in stallion spermatozoa, which are apparently involved in the regulation of the viability of these cells.
Potential role of poly(ADP-ribose) polymerase activation in the pathogenesis of experimental left varicocele.
Tekcan M, Koksal IT, Tasatargil A … +3 more , Kutlu O, Gungor E, Celik-Ozenci C
J Androl · 2012 · PMID 21436309 · Publisher ↗
The aim of this study was to evaluate whether the poly(adenosine diphosphate[ADP]-ribose) polymerase (PARP) pathway is activated by experimental left varicocele. Rats underwent partial ligation of the left renal vein to...
The aim of this study was to evaluate whether the poly(adenosine diphosphate[ADP]-ribose) polymerase (PARP) pathway is activated by experimental left varicocele. Rats underwent partial ligation of the left renal vein to induce experimental varicocele, and left testes were analyzed 13 weeks after surgery. Tubule degeneration was evaluated by Johnsen score. Expression of 4-hydroxy-2-nonenal (4-HNE)-modified proteins, PARP-1, and poly(-ADP-ribose) (PAR) was detected by immunohistochemistry and Western blot. The degree of apoptosis within testes was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling. Light microscopy revealed testicular damage comprising various degrees of seminiferous tubule degeneration. Germ cell apoptotic index and 4-HNE, PAR, and PARP-1 expression in germ cells increased after varicocele induction. Increased oxidative stress and PARP overactivation in testes might be important with regard to impaired testicular function associated with varicocele.
The association of smoking and erectile dysfunction: results from the Fangchenggang Area Male Health and Examination Survey (FAMHES).
Wu C, Zhang H, Gao Y … +7 more , Tan A, Yang X, Lu Z, Zhang Y, Liao M, Wang M, Mo Z
J Androl · 2012 · PMID 21436308 · Publisher ↗
To describe the prevalence of erectile dysfunction (ED) and its association with smoking and other risk factors among a large male population. Data were collected from 2686 men attending the Fangchenggang Area Male Healt...
To describe the prevalence of erectile dysfunction (ED) and its association with smoking and other risk factors among a large male population. Data were collected from 2686 men attending the Fangchenggang Area Male Health and Examination Survey from September 2009 to December 2009. ED was assessed using the 5-item International Index of Erectile Function. Self-reported smoking history was obtained from the questionnaire. Prevalence of ED was 49.5% among 2686 Chinese men in Fangchenggang aged 20-79 years. After adjusting for age, alcohol drinking, physical activity, hypertension, diabetes, dyslipidemia, and obesity, smokers who smoked ≥20 cigarettes daily had a significantly increased risk of ED than never smokers (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.03-1.49; P = .02). After further adjustment for education, the risk of ED was still significantly higher in men smoking more than 23 years than never smokers (OR, 1.60; 95% CI, 1.22-2.09; P = .001). Association of age and education with ED was statistically significant after adjusting for the other variables. A history of diabetes and hypertension all increased the risk of ED, but statistically significant differences did not exist after adjustment for other variables. The association between smoking and ED risk in men was higher with a habit of drinking alcohol (OR, 1.32; 95% CI, 1.01-1.74) or physical inactivity (OR, 1.33; 95% CI, 1.05-1.67), or with a with a history of hypertension (OR, 1.71; 95% CI, 1.11-2.62), dyslipidemia (OR, 1.39; 95% CI, 1.06-1.81), and diabetes (OR, 2.69; 95% CI, 1.4-6.98). Our results show that heavy smoking might cause ED and that the duration of the habit increases the risk of ED. Furthermore, it highlights the potential interaction of smoking with other life habits or medical history on ED risk.
Acupuncture for chronic nonbacterial prostatitis/chronic pelvic pain syndrome: a systematic review.
Posadzki P, Zhang J, Lee MS … +1 more , Ernst E
J Androl · 2012 · PMID 21436307 · Publisher ↗
The objective of this systematic review was to assess the effectiveness of acupuncture as a treatment option for chronic prostatitis/chronic pelvic pain syndrome. Eight databases were searched from their inception to Oct...
The objective of this systematic review was to assess the effectiveness of acupuncture as a treatment option for chronic prostatitis/chronic pelvic pain syndrome. Eight databases were searched from their inception to October 2010. Randomized clinical trials (RCT) were considered if they tested acupuncture against any control intervention or no therapy in humans with chronic prostatitis/chronic pelvic pain syndrome. The selection of studies, data extraction, and validation were performed independently by 2 reviewers. The methodologic quality of all included RCTs was assessed using the Jadad scale. Studies of stimulation of acupoints other than by needles were excluded. Nine RCTs met the inclusion criteria. They all suggested that acupuncture is effective as a range of control interventions. Their methodologic quality was variable; most were associated with major flaws. Only one RCT had a Jadad score of more than 3. The evidence that acupuncture is effective for chronic prostatitis/chronic pelvic pain syndrome is encouraging but, because of several caveats, not conclusive. Therefore, more rigorous studies seem warranted.
Localization, distribution, and function of the calcium-sensing receptor in sperm.
Mendoza FJ, Perez-Marin CC, Garcia-Marin L … +4 more , Madueño JA, Henley C, Aguilera-Tejero E, Rodriguez M
J Androl · 2012 · PMID 21393549 · Publisher ↗
The intracellular movement of calcium, through calcium channels, plays a major role on sperm cell function. The calcium-sensing receptor (CaSR), a molecular mechanism by which many cells detect changes in extracellular c...
The intracellular movement of calcium, through calcium channels, plays a major role on sperm cell function. The calcium-sensing receptor (CaSR), a molecular mechanism by which many cells detect changes in extracellular calcium concentration, has not been described in spermatozoa. The aim of this study was to investigate the expression of the CaSR in testicular tissue and sperm cells and the functional consequences of spermatozoid CaSR activation by calcimimetics. CaSR mRNA and protein were identified both in rat testicular tissue and in rat spermatozoa using real-time reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. Functionality of CaSR was evaluated by studying the influence of calcimimetic AMG 641 on rat and pig sperm motility. Treatment with AMG 641 100 nM for 1 hour increased rat sperm motility from a score of 1.0 ± 0.1 to 3.8 ± 0.3 (P < .05). AMG 641 also resulted in a modest but significant increase in the pig sperm motility parameters evaluated by computer-assisted sperm analysis. AMG 641 was effective in a wide range of concentrations but resulted in a more marked effect at 50-100 nM. In addition, AMG 641 did not have any negative effect on sperm viability, which was measured by flow cytometry. In conclusion, our results demonstrate the expression of functional CaSR in testicular tissue and sperm, which can be activated by calcimimetic AMG 641.
Analysis of 6 single-nucleotide polymorphisms in the androgen receptor gene in Chilean patients with primary spermatogenic failure.
Parada-Bustamante A, Lardone MC, Valdevenito R … +5 more , Ebensperger M, López PV, Madariaga M, Piottante A, Castro A
J Androl · 2012 · PMID 21393548 · Publisher ↗
Androgens are essential for spermatogenesis. It has been postulated that androgen activity is modulated directly or indirectly by genetic variability in the androgen receptor gene sequence, including CAG/GGN polymorphism...
Androgens are essential for spermatogenesis. It has been postulated that androgen activity is modulated directly or indirectly by genetic variability in the androgen receptor gene sequence, including CAG/GGN polymorphisms and single-nucleotide polymorphisms (SNP). In this study, the frequency of 6 SNPs that constitute a haplotype in the androgen receptor sequence was determined by enzyme restriction assays and allele-specific polymerase chain reactions in 117 secretory azo/oligozoospermic men (93 idiopathic and 24 excryptorchidic), and in 121 controls with normal spermatogenesis (42 obstructive and 79 normozoospermic men) whose hormonal measurements and length of CAG/GGN polymorphisms were previously determined. The frequency of these 6 SNPs was not different between patients and controls. A total of 10 haplotypes (HAPs 1-10) formed by these 6 SNPs were found, and one of these haplotypes was observed with high frequency in the total population (HAP1, 83.2%; P < .001, χ(2) test). The frequency of the 10 haplotypes was not different between patients and controls, except for HAP5, which was only detected in one patient with a history of bilateral cryptorchidism (P = 0.014, Bonferroni test). On the other hand, no associations were found between the haplotypes studied and shorter or longer CAG or GGN polymorphisms. Interestingly, we found that the CAG 21 allele, which was previously correlated with an increased risk of idiopathic spermatogenic impairment, was more frequently found among the less common haplotypes that have higher follicle-stimulating hormone serum levels. In summary, we did not find an increased frequency of particular haplotypes in infertile men with idiopathic spermatogenic impairment compared with control men; however, we found that the CAG 21 allele, which appears to be associated with male infertility, is observed at a significantly higher proportion among the less common androgen receptor haplotypes.
Nonsurgical interventions for Peyronie disease: 2011 update.
Schaeffer AJ, Burnett AL
J Androl · 2012 · PMID 21350241 · Publisher ↗
Peyronie disease (PD) arises from the deposition of collagen and fibrin that creates a plaque in the tunica albuginea of the penis. The resulting induration and curvature of the penis leads to sexual dysfunction in many...
Peyronie disease (PD) arises from the deposition of collagen and fibrin that creates a plaque in the tunica albuginea of the penis. The resulting induration and curvature of the penis leads to sexual dysfunction in many men. Despite the prevalence of the disease and natural history studies that suggest progression, men might not seek therapeutic intervention due to a lack of general knowledge about the disease, its pathophysiology, and treatments aimed at ameliorating its symptoms. Medical therapy using oral, topical, or intralesionally delivered drug is pursued in all but the most severe cases. This review of the literature in the last 4 years attempts to identify new trials of therapies and treatment modalities aimed at altering the PD process. Specifically, we will address clinical trials evaluating oral pharmacotherapies; topical, intralesional, and shockwave therapies; and penile traction devices. We will discuss the level of evidence and support for each of the new clinical trials.
Association of TNFα, TNFR1, and TNFR2 polymorphisms with sperm concentration and motility.
Lazaros LA, Xita NV, Chatzikyriakidou AL … +7 more , Kaponis AI, Grigoriadis NG, Hatzi EG, Grigoriadis IG, Sofikitis NV, Zikopoulos KA, Georgiou IA
J Androl · 2012 · PMID 21350240 · Publisher ↗
Tumor necrosis factor α (TNFα) is a multifunctional cytokine that regulates various cellular processes related to spermatogenesis. Two types of cell receptors, TNFR1 and TNFR2, mediate TNFα activity. In the present study...
Tumor necrosis factor α (TNFα) is a multifunctional cytokine that regulates various cellular processes related to spermatogenesis. Two types of cell receptors, TNFR1 and TNFR2, mediate TNFα activity. In the present study, we sought to explore the association of TNFα -857C→T, TNFR1 36A→G, and TNFR2 676T→G polymorphisms with sperm concentration and motility. Two hundred ninety men were examined during infertility investigation; of those, 170 men were normozoospermic and 120 were oligospermic. Polymerase chain reaction analysis revealed significant differences in genotype distribution of the TNFR1 36A→G polymorphism between normozoospermic and oligospermic men. Men with oligozoospermia presented TNFR1 36A/A genotypes less frequently than normozoospermic men (P < .001). The presence of the TNFR1 36G allele was significantly increased in oligospermic men (P < .001). Furthermore, the presence of the TNFR1 36G allele was associated with lower sperm concentration in normozoospermic men (P < .03) and in the total study population (P < .001), and with lower sperm motility in normozoospermic men (P < .007) and in the total study population (P < .001). No significant associations were found between TNFα -857C→T and TNFR2 676T→G polymorphisms and semen quality. The TNFR1 36A allele is associated with increased sperm concentration and motility in our series, supporting the significance of TNFR1 gene in semen quality.
Flow cytometry TUNEL standardization for assaying sperm DNA fragmentation.
Curi SM, Chenlo PH, Billordo LA … +6 more , Baz P, Sardi ML, Ariagno JI, Repetto H, Mendeluk GR, Pugliese MN
J Androl · 2012 · PMID 21350239 · Publisher ↗
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Negative androgen-response elements mediate androgen-dependent transcriptional inhibition of TGF-β1 and CDK2 promoters in the prostate gland.
Qi W, Gao S, Chu J … +2 more , Zhou L, Wang Z
J Androl · 2012 · PMID 21350238 · Publisher ↗
The androgen receptor (AR) is a ligand-dependent transcription factor that mediates androgen functions by regulating the expression of genes it targets. In the present study, we mapped 2 regions in human transforming gro...
The androgen receptor (AR) is a ligand-dependent transcription factor that mediates androgen functions by regulating the expression of genes it targets. In the present study, we mapped 2 regions in human transforming growth factor β1 and cyclin-dependent kinase 2 promoters that negatively regulated transcriptional activity in an androgen-dependent manner in close proximity to positive androgen-response elements (pARE). We identified 7 negative androgen-response elements (nARE) in the negative androgen-response region in the TGF-β1 promoter. Each nARE is composed of 15 nucleotides and mediates androgen-dependent inhibition of transcription in close proximity of pAREs. The 5' portions of nAREs are highly conserved and resemble core half sites in pAREs. The nAREs interacted weakly with AR DNA-binding domain (AR DBD) in gel shift assays. Mutations on the conserved nucleotides in the nARE abolished its interaction with the AR DBD and abolished its inhibition of androgen-driven transcription, suggesting that nARE/AR interaction is essential for nARE-mediated inhibition of transcription. Taken together, these findings indicate that the AR negatively regulates the expression of its target genes via a negative androgen-response region composed of multiple nAREs.
Functional cooperation between GATA factors and cJUN on the star promoter in MA-10 Leydig cells.
Martin LJ, Bergeron F, Viger RS … +1 more , Tremblay JJ
J Androl · 2012 · PMID 21350237 · Publisher ↗
Steroid hormone biosynthesis requires the steroidogenic acute regulatory protein (STAR). STAR is part of a protein complex that transports cholesterol through the mitochondrial membrane where steroidogenesis begins. Seve...
Steroid hormone biosynthesis requires the steroidogenic acute regulatory protein (STAR). STAR is part of a protein complex that transports cholesterol through the mitochondrial membrane where steroidogenesis begins. Several transcription factors participate to direct the proper spatiotemporal and hormonal regulation of the Star gene in Leydig cells. Mechanistically, this is believed to involve the functional interplay between many of these factors. Here we report a novel transcriptional cooperation between GATA factors and cJUN on the mouse Star and human STAR promoters in MA-10 Leydig cells. This cooperation was observed with different GATA members (GATA1, 4, and 6), whereas only cJUN could cooperate with GATA factors. GATA/cJUN transcriptional cooperation on the Star promoter is mediated via closely juxtaposed GATA and AP-1 binding motifs. Mutation of all functional GATA and cJUN elements abolished GATA/cJUN cooperation, which is in agreement with previous data reporting a direct interaction between GATA4 and cJUN in a heterologous system. These data add valuable new insights that further define the molecular mechanisms that govern Star transcription in steroidogenic cells of the testis.
Simultaneous accumulation of hyaluronan binding protein 1 (HABP1/p32/gC1qR) and apoptotic induction of germ cells in cryptorchid testis.
Kumar V, Misro MM, Datta K
J Androl · 2012 · PMID 21311052 · Publisher ↗
In the experimentally cryptorchid rat, spermatogenic arrest is associated with the formation of multinuclear giant cells, leading to large-scale apoptosis and elimination of germ cells from the seminiferous epithelium. U...
In the experimentally cryptorchid rat, spermatogenic arrest is associated with the formation of multinuclear giant cells, leading to large-scale apoptosis and elimination of germ cells from the seminiferous epithelium. Using this model, the role of Hyaluronan Binding Protein 1 (HABP1), which expresses a stage specifically in post-meiotic cells during spermatogenesis, was examined. Cryptorchidism induced complete arrest of spermatogenesis by 2 days, and by 3-5 days many large and small multinucleated giant cells populated the affected tubules. Ultrastructure of the giant cells revealed both single and multiple chromatin aggregation, with some less compact and distorted, and others broken down into tiny fragments. These cells along with other germ cells were stained terminal deoxynucleotidyl transferase dUTP nick-end labeling positive, demonstrating strong expression of Bax and Heat Shock Protein 70. Simultaneously, there was an up-regulation of the proprotein form of HABP1 in these cells and a decrease in the mature form of protein. The above findings indicate a possible role for HABP1 proprotein in apoptosis induction of germ cells in the cryptorchid testes.
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