Recent studies have shown significant associations of aberrant DNA methylation in spermatozoa with idiopathic male infertility, increased frequency of spontaneous abortions and imprinting disorders. Thus, the analysis of DNA methylation of specific genes in spermatozoa has the potential to become a new valuable diagnostic marker in clinical andrology. This perspective article discusses the current state and value of DNA methylation analysis in the diagnostic setup of infertile men and outlines challenges and perspectives. It highlights the potential of DNA methylation in andrological diagnostics and its putative benefit in the examination of hitherto idiopathic infertile patients is described.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

It is well-documented that male overweight and obesity causes endocrine disorders that might diminish the male reproductive capacity; however, reports have been conflicting regarding the influence of male body mass index (BMI) on semen quality and the outcome of assisted reproductive technology (ART). The aim of this study was to investigate whether increased male BMI affects sperm quality and the outcome of assisted reproduction in couples with an overweight or obese man and a non-obese partner. Data was prospectively collected from 612 infertile couples undergoing ART at a Danish fertility center. Self-reported information on paternal height and weight were recorded and BMI was calculated. The men were divided into four BMI categories: underweight BMI < 20 kg m⁻² , normal BMI 20-24.9 kg m⁻² , overweight BMI 25-29.9 kg m⁻² and obese BMI > 30 kg m⁻² . Conventional semen analysis was performed according to the World Health Organization guideline and sperm DNA integrity was analyzed by the Sperm Chromatin Structure Assay (SCSA). No statistically significant effect of male BMI was seen on conventional semen parameters (sperm concentration, total sperm count, seminal volume and motility) or on SCSA-results. Furthermore, the outcome of ART regarding fertilization rate, number of good quality embryos (GQE ), implantation and pregnancy outcome was not influenced by the increasing male BMI.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

To analyze the learning curve for cancer control from an initial 250 cases (Group I) and subsequent 250 cases (Group II) of robotic-assisted laparoscopic radical prostatectomy (RALP) performed by a single surgeon. Five hundred consecutive patients with clinically localized prostate cancer received RALP and were evaluated. Surgical parameters and perioperative complications were compared between the groups. Positive surgical margin (PSM) and biochemical recurrence (BCR) were assessed as cancer control outcomes. Patients in Group II had significantly more advanced prostate cancer than those in Group I (22.2% vs 14.2%, respectively, with Gleason score 8-10, P= 0.033; 12.8% vs 5.6%, respectively, with clinical stage T3, P= 0.017). The incidence of PSM in pT3 was decreased significantly from 49% in Group I to 32.6% in Group II. A meaningful trend was noted for a decreasing PSM rate with each consecutive group of 50 cases, including pT3 and high-risk patients. Neurovascular bundle (NVB) preservation was significantly influenced by the PSM in high-risk patients (84.1% in the preservation group vs 43.9% in the nonpreservation group). The 3-year, 5-year, and 7-year BCR-free survival rates were 79.2%, 75.3%, and 70.2%, respectively. In conclusion, the incidence of PSM in pT3 was decreased significantly after 250 cases. There was a trend in the surgical learning curve for decreasing PSM with each group of 50 cases. NVB preservation during RALP for the high-risk group is not suggested due to increasing PSM.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

We aimed to determine the mechanisms of the anabolic actions of androgens in skeletal muscle by investigating potential androgen receptor (AR)-regulated genes in in vitro and in vivo models. The expression of the myogenic regulatory factor myogenin was significantly decreased in skeletal muscle from testosterone-treated orchidectomized male mice compared to control orchidectomized males, and was increased in muscle from male AR knockout mice that lacked DNA binding activity (AR^ΔZF2 ) versus wildtype mice, demonstrating that myogenin is repressed by the androgen/AR pathway. The ubiquitin ligase Fbxo32 was repressed by 12 h dihydrotestosterone treatment in human skeletal muscle cell myoblasts, and c-Myc expression was decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle, and increased in AR^∆ZF2 muscle. The expression of a group of genes that regulate the transition from myoblast proliferation to differentiation, Tceal7 , p57 ^Kip2, Igf2 and calcineurin Aa, was increased in AR^∆ZF2 muscle, and the expression of all but p57 ^Kip2 was also decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle. We conclude that in males, androgens act via the AR in part to promote peak muscle mass by maintaining myoblasts in the proliferative state and delaying the transition to differentiation during muscle growth and development, and by suppressing ubiquitin ligase-mediated atrophy pathways to preserve muscle mass in adult muscle.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Various methods are currently under investigation to preserve fertility in males treated with high-dose chemotherapy and radiation for malignant and nonmalignant disorders. Human umbilical cord mesenchymal stem cells (HUC-MSCs), which possess potent immunosuppressive function and secrete various cytokines and growth factors, have the potential clinical applications. As a potential alternative, we investigate whether injection of HUC-MSCs into the interstitial compartment of the testes to promote spermatogenic regeneration efficiently. HUC-MSCs were isolated from different sources of umbilical cords and injected into the interstitial space of one testis from 10 busulfan-treated mice (saline and HEK293 cells injections were performed in a separate set of mice) and the other testis remained uninjected. Three weeks after MSCs injection, Relative quantitative reverse transcription polymerase chain reaction was used to identify the expression of 10 of germ cell associated, which are all related to meiosis, demonstrated higher levels of spermatogenic gene expression (2-8 fold) in HUC-MSCs injected testes compared to the contralateral uninjected testes (five mice). Protein levels for germ cell-specific genes, miwi, vasa and synaptonemal complex protein (Scp3) were also higher in MSC-treated testes compared to injected controls 3 weeks after treatment. However, no different expression was detected in saline water and HEK293 cells injection control group. We have demonstrated HUC-MSCs could affect mouse germ cell-specific genes expression. The results also provide a possibility that the transplanted HUC-MSCs may promote the recovery of spermatogenesis. This study provides further evidence for preclinical therapeutic effects of HUC-MSCs, and explores a new approach to the treatment of azoospermia.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Dapoxetine hydrochloride is a selective serotonin reuptake inhibitor and the first drug approved for the on-demand treatment of premature ejaculation (PE). Our objective in this study was to characterize the efficacy of on-demand dapoxetine (30 and 60 mg) and daily paroxetine (20 mg) usage in treating PE. We conducted a 1 month study involving a total of 150 patients. Patients were divided into three groups of 50. Group 1 were treated with on-demand dapoxetine (30 mg), Group 2 with on-demand dapoxetine (60 mg) and Group 3 with daily paroxetine (20 mg). Our outcome measurement was increased from baseline intravaginal ejaculatory latency time (IELT) after treatment. The IELT increased from baseline to posttreatment by 117%, 117% and 170% in the paroxetine group (P < 0.01), 30 mg dapoxetine group (P < 0.01) and 60 mg dapoxetine group (P < 0.01), respectively. The increase from baseline IELT were similar for the 30 mg dapoxetine and paroxetine groups (P > 0.05), while the 60 mg dapoxetine group had a larger posttreatment IELT increase compared with the 30 mg dapoxetine (P < 0.05) and paroxetine (P < 0.01) groups. Dapoxetine (60 mg) 1-3 h before planned intercourse is a very effective treatment modality for PE. However, an on-demand dose of 30 mg dapoxetine is no more effective than the currently prescribed paroxetine treatment.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Childhood inguinal herniorrhaphy is one common cause of seminal tract obstruction. Vasovasostomy (VV) can reconstruct seminal deferens and result in appearance of sperm and natural pregnancy in some patients. Secondary epididymal obstruction caused by a relatively long-term vasal obstruction is a common cause of lower patency compared with VV due to vasectomy in adults. From July 2007 to June 2012, a total of 62 patients, with history of childhood inguinal herniorrhaphy and diagnosed as obstructive azoospermia were treated in our center. The overall patency rate and natural pregnancy rate were 56.5% (35/62) and 25.8% (16/62), respectively. 48.4% (30/62) of the patients underwent bilateral VV in the inguinal region, with a patency rate of 76.7% (23/30) and a natural pregnancy rate of 36.7% (11/30), respectively. 30.6% (19/62) of the patients underwent bilateral VV and unilateral or bilateral vasoepididymostomies due to ipsilateral epididymal obstruction with the patency and natural pregnancy rate decreasing to 63.2% (12/19) and 26.3% (5/19). 21.0% (13/62) of the patients merely underwent vasal exploration without reconstruction due to failure to find distal vasal stump, etc. Our study indicate that microsurgical reanastomosis is an effective treatment for some patients with seminal tract obstruction caused by childhood inguinal herniorrhaphy.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

This study was undertaken to evaluate the influence of treatment with rifaximin followed by the probiotic VSL#3 versus no treatment on the progression of chronic prostatitis toward chronic microbial prostate-vesiculitis (PV) or prostate-vesiculo-epididymitis (PVE). A total of 106 selected infertile male patients with bacteriologically cured chronic bacterial prostatitis (CBP) and irritable bowel syndrome (IBS) were randomly prescribed rifaximin (200 mg, 2 tablets bid, for 7 days monthly for 12 months) and probiotic containing multiple strains VSL#3 (450 × 10 ^[9] CFU per day) or no treatment. Ninety-five of them (89.6%) complied with the therapeutic plan and were included in this study. Group A = "6Tx/6-": treatment for the initial 6 and no treatment for the following 6 months (n = 26); Group B = "12Tx": 12 months of treatment (n = 22); Group C = "6-/6Tx": no treatment for the initial 6 months and treatment in the last 6 months (n = 23); Group D = "12-": no treatment (n = 24). The patients of Groups A = "6Tx/6-" and B = "12Tx" had the highest frequency of chronic prostatitis (88.5% and 86.4%, respectively). In contrast, group "12-": patients had the lowest frequency of prostatitis (33.4%). The progression of prostatitis into PV in groups "6Tx/6-" (15.5%) and "6-/6Tx" (13.6%) was lower than that found in the patients of group "12-" (45.8%). Finally, no patient of groups "6Tx/6-" and "6-/6Tx" had PVE, whereas it was diagnosed in 20.8% of group "12-" patients. Long-term treatment with rifaximin and the probiotic VSL#3 is effective in lowering the progression of prostatitis into more complicated forms of male accessory gland infections in infertile patients with bacteriologically cured CBP plus IBS.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

To investigate the prevalence, correlates, attitude and treatment seeking behavior of erectile dysfunction (ED) in type 2 diabetes mellitus (T2DM) patients in the primary care setting, a multi-center cross-sectional survey using a structured anonymous self-administered questionnaire was performed in 10 general outpatient clinics. Of the 603 subjects (91% response rate), the prevalence of ED men, as defined by the International Index of Erectile Function, was 79.1%. Most subjects had mild ED (28.9%), followed by mild-to-moderate ED (27.9%), then moderate ED (13.4%) and severe ED (9%). Nearly 55% of those with ED did not consider themselves as having ED. Less than 10% of them had ever sought medical treatment, although 76.1% of them wished to receive management from doctor(s) should they be diagnosed with ED. They considered the most important management from doctors to be clinical assessment (41.7%), followed by management of potential underlying cause (37.8%), referral to specialist (27.5%), education (23.9%), prescription of phosphodiesterase type 5 inhibitors (16.9%) and referral to counseling service (6.7%). The prevalence of ED was strongly associated with subjects who thought they had ED (odds ratio (OR) = 90.49 (20.00-409.48, P< 0.001)) and were from the older age group (OR = 1.043 (1.011-1.076, P= 0.008)). In conclusion, ED is highly prevalent among T2DM men. The majority of them wanted management from doctors should they have ED, but only a minority would actually voice out the request. Screening of ED among T2DM men using structural questionnaire allowed the diagnosis of more than half of the ED cases, which otherwise would have gone undiagnosed.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Male accessory gland inflammation or infection (MAGI) is a potentially underdiagnosed complication of type 2 diabetes (DM2); specifically, we reported in a recent study that the frequency of MAGI was 43% among DM2 patients. In previous studies, we have demonstrated that diabetic autonomic neuropathy (DAN) is associated with a peculiar ultrasound characterization of the seminal vesicles (SVs) in DM2 patients. The aim of the present study was to evaluate the frequency of MAGI in two different categories of DM2 patients (i.e. patients with and without symptoms that possibly reflect DAN) and the respective ultrasound characterizations. Sixty DM2 patients with a mean (± s.e.m.) age of 42.0 ± 6.0 years (range: 34-47 years) were classified according to the presence or the absence of symptoms that could possibly reflect DAN (group A: DM2 with symptoms possibly reflecting DAN, n = 28 patients and group B: DM2 without symptoms possibly reflecting DAN, n = 32 patients). The patients in Group A exhibited a significantly higher frequency of MAGI compared with those in group B patients (P < 0.05); moreover, the Group A patients exhibited a significantly higher frequency of ultrasound signs suggestive of vesiculitis (P < 0.05). Finally, the concentrations of lymphocytes but not the concentrations of the leukocytes in the semen were significantly higher (P < 0.05) in group A compared with group B.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Whether the 370-371insACA, 494T>C, and 1423C>T haplotype in ubiquitin-specific protease 26 (USP26) gene is associated with male infertility is controversial. To clarify this issue, we conducted a meta-analysis based on the most recent studies. Eligible studies were screened by using PubMed and Embase. Pooled odd ratio (OR) with 95% confidence interval (CI) was calculated with fixed effect models. Ten studies with 1603 patients and 2505 controls were included. Overall, the results indicated that there was an association between the haplotype and male infertile risk (OR = 1.74, 95% CI: 1.09-2.77). The OR calculated based on the five studies in Asia and three in Europe was 1.96 (95% CI: 1.05-3.67) and 1.54 (95% CI: 0.75-3.16) respectively, however, the OR was 0.86 (95% CI: 0.05-15.29) based on the two investigations in America. In addition, the data from the patients with azoospermia (AZO) showed an increased pooled OR of 2.35 (95% CI: 1.22-4.50). In contrast, the studies with oligoasthenoteratozoospermia (OAT) exhibited that the pooled OR was 0.97 (95% CI: 0.43-2.16). Our analyses indicate that there is an association of alteration in USP26 with male infertility, especially in AZO and Asian population.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

The aim of this study was to design a molecular assay for the diagnosis of Klinefelter syndrome (KS), based on the detection of supernumerary X-chromosomes (X-chs). DNA was extracted from peripheral blood samples of twenty-six 47,XXY males; two 46,XY/47,XXY males; twenty-two 46,XY males; and 15 females; and deaminated. Methylation-specific quantitative polymerase chain reaction (MS-qPCR) was performed using primers for unmethylated and methylated copies of the X-ch inactive-specific transcript (XIST-U and XIST-M) gene. X-ch disomy was determined on the basis of XIST methylation status. Degree of mosaicism in the 46,XY/47,XXY males was compared with karyotype and fluorescent in situ hybridization (FISH) results. Data analysis was performed using the Roche® LightCycler software V. 3.5.3., including determination of crossing points (CPs) by fit-point analysis and melting curve analysis. X-ch disomy was detected in all female controls and KS patients; male controls expressed XIST-M only. CPs ranged from 29.5 to 32.5 (standard deviation (s.d.) 0.8) for XIST-U and from 29 to 31 (s.d. 0.6) for XIST-M. Limit of detection of mosaicism was 1%. Based on XIST-U/XIST-M ratios for the two 47,XXY/46,XY patients, the calculated degree of mosaicism (1.8% and 17.8%) was comparable to FISH results (2.3% and 15%, respectively). Turnaround time from DNA deamination to final data analysis was under 9 h. We conclude that MS-qPCR is a sensitive, specific and rapid test for the detection of X-ch disomy, with applicability for the screening and diagnosis of KS, even in the setting of low grade 47,XXY/46,XY mosaicism.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Reactive stromal changes in prostate cancer (PCa) are likely involved in the emergence of castration-resistant PCa (CRPC). This study was designed to investigate stromal changes in patients with clinically advanced PCa and analyze their prognostic significance. Prostate needle biopsies obtained from 148 patients before castration therapy were analyzed by Masson trichrome staining and immunohistochemical analysis of vimentin and desmin. Reactive stroma grading was inversely correlated with Gleason score. Stroma grade (Masson stain 82.8% vs 45.6%, P < 0.001) and vimentin expression (P = 0.005) were significantly higher, and desmin expression (P = 0.004) significantly lower, in reactive stroma of tumors with a Gleason score of 6-7 than in adjacent peritumoral tissue. Kaplan-Meier analysis showed a significant association between reactive stroma grade in tumors and the occurrence of CRPC in patients with a Gleason score of 6-7 (P = 0.009). Furthermore, patients with higher vimentin or lower desmin expression had a shorter disease-free period. In multivariate analysis, only vimentin expression was a significant predictor of tumor relapse (hazard ratio 1.78, 95% confidence interval 1.12-10.26, P = 0.012). These findings indicate that the intensity of reactive stroma is associated with castration responsiveness, especially in patients with a lower Gleason score where the abundant stroma component is most frequently found. High expression of vimentin in tumor stroma was independently associated with poor outcomes in patients with Gleason scores of 6-7, and may serve as a new prognostic marker in daily practice.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

To examine the outcomes of patients with high-risk prostate cancer (PCa) treated by robot-assisted radical prostatectomy (RARP) and evaluate the value of multi-parametric magnetic resonance imaging (MRI) in estimating tumor stage, extracapsular extension, and grade, and the application of nerve sparing (NS) techniques. Patient demographics, preoperative imaging, surgical parameters, pathological features, functional and recurrence outcomes were collected retrospectively in patients with high-risk PCa who underwent RARP between December 2009 and October 2013. Pathological whole mount slides to assess NS were compared with potency, recovery of continence, and surgical margins (SM). Forty-four cases of high-risk PCa were identified with a median followup of 24 months and positive surgical margins (PSM) rate of 14%. Continence returned in 86%, with potency rate of 58%. Of the 25 cases with a preoperative multi-parametric MRI, MRI improved clinical staging from 28% to 88%, respectively. Following risk stratification of NS by microscopic analysis of whole mount pathology, patients with Group A (bilateral NS), Group B (unilateral NS), Group C (partial NS), and Group D (non-NS) had 100%, 92%, 91%, and 50% continence rates, and 100%, 80%, 45%, and 0% potency rates, respectively, with an inverse correlation to PSM. RARP in men with high-risk PCa can achieve favorable oncologic and functional outcomes. Preoperative MRI may localize high-grade tumors and improve clinical staging. Extent of NS is influenced by clinical staging and may balance potency and continence with PSMs.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Digito-rectal examination (DRE) of the prostate provides useful information on the state of prostate growth and on the presence of suspected peripheral nodules. The aim of this study is to describe the clinical and biochemical correlates of finding an enlarged prostate size at DRE in subjects with sexual dysfunction (SD). A consecutive series of 2379 patients was retrospectively studied. The analysis was focused on a subset of subjects (n = 1823; mean age 54.7 ± 11.4) selected for being free from overt prostatic diseases. Several parameters were investigated. After adjusting for confounders, the presence of an enlarged prostate size at DRE was associated with a higher risk of metabolic syndrome (HR = 1.346 (1.129-1.759); P = 0.030), type 2 diabetes mellitus (HR = 1.489 (1.120-1.980); P = 0.006), increased LDL cholesterol (>100 mg dl⁻¹ ; HR = 1.354 (1.018-1.801); P = 0.037) and increased mean blood pressure (BP) values (HR = 1.017 (1.007-1.027) for each mmHg increment; P = 0.001). Accordingly, enlarged prostate size was also associated with a higher risk of arteriogenic erectile dysfunction (ED), as well as with other andrological conditions, such as varicocele and premature ejaculation (PE). PSA levels were significantly higher in subjects with enlarged prostate size when compared to the rest of the sample (HR = 3.318 (2.304; 4.799) for each log unit increment in PSA levels; P < 0.0001). Arteriogenic ED, according to different criteria, was also associated with increased PSA levels. In conclusion, our data support the need to examine prostate size either by clinical (DRE) or biochemical (PSA) inspection in subjects with SD, in order to have insights into the nature of the SD and the metabolic and cardiovascular (CV) background of the patient.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

This case-controlled study was designed to evaluate the association between various baseline parental factors and the risk of hypospadias in China. Patients were selected from tertiary referral hospitals in Anhui, a province in mid-eastern China. A questionnaire was given to the parents of each patient. The final database included 193 cases and 835 controls. The incidence of additional coexistent anomalies was 13.0%, primarily cryptorchidism (9.8%). Ten patients (5.1%) were from families with genital anomaly, including five families (2.6%) with hypospadias. The risks of hypospadias was higher for children of mothers > 35 (odds ratio [OR] =1.47) and < 18 (OR = 2.95) years of age, and in mothers who had consumed alcohol (OR = 2.67), used drugs (OR = 1.53) and had an infection (OR = 1.87) during pregnancy. The risk of hypospadias was also higher when mothers (OR = 1.68) and fathers (OR = 1.74) were engaged in agriculture. Other factors assessed were not associated with the risk of hypospadias.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Prostate cancer is one of the most common cancers in men. Traditional screening and diagnostic methods include digital rectal examinations (DREs), biopsies and serum prostate-specific antigen (PSA) tests, with the latter being the more popular. PSA is a biomarker for prostate cancer; however, it is highly sensitive to external factors as well as other prostate diseases. As such, the reliability of of the serum PSA level as a sole screening and diagnostic tool for prostate cancer is controversial. Recently, it has been shown that fasting extremes can affect concentrations of serum chemistry analytes, thus raising the question of whether or not fasting has an effect on the highly sensitive PSA biomarker. Patients testing for serum PSA levels are often concomitantly submitting to other tests that require fasting, subjecting certain patients to a fasting PSA level while others not. The objective of this study was to investigate whether this discrepancy in fasting state translates into an effect on serum PSA levels. Serum PSA levels and fasting time records for 157 276 men who underwent testing at Calgary Laboratory Services (CLS; Calgary, Alberta, Canada) between 01 January 2010 and 31 March 2013 were accessed. Linear regression models of mean PSA levels and fasting times revealed a statistically important relationship at certain fasting times. Applying a dynamic mathematical model to explore the clinical effect of fasting suggests minimal impact on serum PSA result interpretation. Thus, patients can be tested for serum PSA levels regardless of their fasting state.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

SET is a multifunctional protein involved in regulating many biological processes of the cell cycle. It is also a regulator of steroidogenesis in the ovary. However, the expression of SET protein in testis, and its function, still remains ambiguous. In this study, we observed the expression of SET in the testes of mice at different developmental stages, and have discussed its potential function in regulating spermatogenesis and androgen production. Forty-eight male mice at different developmental stages (1 week old as the infancy group; 4 weeks old as the prepubertal group; 12 weeks old as the adult group; over 12 months old as the ageing group) were used. Cellular location of SET protein in the testes was observed by immuno-histochemistry. Expression levels of Set mRNA and SET protein were analyzed by quantitative polymerase chain reaction and Western blotting. SET protein was expressed in spermatogonial cells and spermatocytes; the highest level was mainly in haploid and tetraploid cells of the prepubertal and adult groups, and Leydig cells of the adult and ageing groups. There was a low expression in Sertoli cells. Expression of Set mRNA in the prepubertal group was significantly higher than that in the adult group (P < 0.05), while expression of SET protein was at the highest level in the adult group (P < 0.05). SET protein is mainly expressed in spermatogonial cells and spermatocytes, and poorly expressed in Sertoli cells, suggesting that it is involved in spermatogenesis. Expression of SET protein in Leydig cells suggests a possible role in steroidogenesis.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Monocarboxylic acid transporter 2 (MCT2) transports pyruvate and lactate outside and inside of sperms, mainly as energy sources and plays roles in the regulation of spermatogenesis. We investigated the association among genetic variations in the MCT2 gene, male infertility and MCT2 expression levels in sperm. The functional and genetic significance of the intron 2 (+28201A > G, rs10506398) and 3' untranslated region (UTR) single nucleotide polymorphism (SNP) (+2626G > A, rs10506399) of MCT2 variants were investigated. Two MCT2 polymorphisms were associated with male infertility (n = 471, P < 0.05). In particular, the MCT2-3' UTR SNP (+2626 G > A) had a strong association with the oligoasthenoteratozoospermia (OAT) group. The +2626GG type had an almost 2.4-fold higher sperm count than that of the +2626AA type (+2626GG; 66 × 10 ⁶ vs +2626AA; 27 × 10 ⁶ , P < 0.0001). The MCT2-3' UTR SNP may be important for expression, as it is located at the MCT2 3' UTR. The average MCT2 protein amount in sperm of the +2626GG type was about two times higher than that of the +2626AA type. The results suggest that genetic variation in MCT2 has functional and clinical relevance with male infertility.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Cancer cells often depend on altered metabolism compared with their normal counterparts. ^{[1],[2],[3],[4]} As observed in 1924 by Otto Warburg, cancer cells show preferential glucose consumption by way of aerobic glycolysis while normal cells generally assume mitochondrial oxidative phosphorylation. ^[4] Another metabolic hallmark of carcinogenesis is altered lipid metabolism, whereby cancer cells may adopt enhanced de novo lipid production (lipogenesis). ^[1],[2],[3] Enhanced lipid metabolism is also observed in individuals with metabolic syndromes potentially a consequence of increasing popularity of the Standard American Diet, composed of high levels of saturated fats and carbohydrates. ^[5] A growing body of epidemiological data indicates a positive correlation between the occurrence of metabolic syndromes, such as cardiovascular disease, obesity, type-2 diabetes and associated hyperinsulemia, with the aggressiveness of cancer. ^{[6],[7],[8],[9]} Remarkably, it is estimated that for every 1% reduction in saturated fats, replaced by polyunsaturated, there would be a 2%-3% reduction in cardiovascular disease. ^[10] Thus, it is conceivable that an equally remarkable attenuation in cancer progression might be achieved with such a reduction in lipid accumulation.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

The predictive factors of prognosis and treatment strategies for small-cell carcinoma (SCC) of the urinary tract are controversial. This study was aimed to investigate the clinical experience and management of patients with SCC of the urinary tract. We collected data of patients who were diagnosed with genitourinary SCC (GSCC) between 2002 and 2013 and were treated in the Fudan University Shanghai Cancer Center. A total of 18 patients were diagnosed with GSCC of which 10 originated from the prostate, seven from the bladder and one from the adrenal gland. The mean follow-up time was 15.5 months and progression-free survival (PFS) was 9.3 months. Primary tumor resection was attempted in 13 of 18 patients (72.2%) in whom radical surgery was performed in six of 14 (42.9%) limited disease patients. Most of the patients (13, 72.2%) received cisplatin-based chemotherapy. Patients who had normal lactic dehydrogenase (LDH) levels showed a significantly higher median PFS and overall survival (OS) compared with patients with high LDH levels (P = 0.030, P= 0.010). Patients with limited disease treated with a radical operation experienced a non-significant (P = 0.211) longer PFS compared with patients who were not treated, but this reached statistical significance after analyzing OS (P = 0.211, P= 0.039). Our patients showed a poor prognosis as reported previously. Serum LDH levels beyond the normal range indicate a poor prognosis. For GSCC patients who are diagnosed with limited disease, radical surgery is strongly recommended along with cisplatin-based chemotherapy.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Recent reports and discussions of preclinical prostate cancer models have emphasized the possibility that enzalutamide resistance may be mediated by glucocorticoid receptors (GR). ^[1],[2] In both in vitroand xenograft animal studies, it is possible to show that the GR is up-regulated in prostate cancer cell lines and that dexamethasone reverses enzalutamide induced growth inhibition. In these model systems, GR agonists can induce a subset of androgen receptor target genes including prostate-specific antigen. These investigators also report a correlation between GR expression in patient-derived prostate cancer specimens and clinical response to enzalutamide. The authors discuss the possibility that these findings have important clinical relevance. We note that the current clinical evidence for GR mediating drug resistance or disease progression in patients with castrate-resistant prostate cancer (CRPC) is very limited at best.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Some published evidence has revealed that the dendritic cells can interact with pathogens that exist in the inner foreskin. This information provides a new vision that pathogens could play a role through the redundant prepuce; numerous studies have failed to find pathogens in prostates of patients who had chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, no studies have reported an association between foreskin length and CP/CPPS. Hence, we conducted a retrospective case-control study of clinical data from 322 CP/CPPS patients (case group) and 341 nonCP/CPPS patients (control group). Demographic characteristics, lifestyle factors, and foreskin lengths were collected and analyzed. Multivariate logistic regression was adopted to calculate the odds of foreskin length for CP/CPPS. According to the multivariate logistic regression results, when the foreskin length covered up more than half of the glans penis, the odds for CP/CPPS were higher with an increased foreskin (odds ratio (OR): 1.66, 95% confidence interval (CI): 1.04-2.66). In comparison, when the glans penis was completely covered by the foreskin, the OR value increased to 1.86 (95% CI, 1.2-2.88). The study results showed an association between foreskin length and the odds of CP/CPPS. When the foreskin length covered up more than half of the glans penis, there were greater odds for CP/CPPS. This possible mechanism might result from interaction between pathogens and DCs in the inner foreskin, consequently activating T-cells to mediate allergic inflammation in the prostate and producing the autoimmunizations causing CP/CPPS.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Large scale exome sequencing studies have revealed regions of the genome, which contribute to the castrate resistant prostate cancer (CRPC) phenotype. ^[1],[2],[3] Such studies have identified mutations in genes, which may have diagnostic/prognostic potential, or which may be targeted therapeutically. Two of these genes include the androgen receptor (AR) and speckle-type POZ protein (SPOP) genes. However, the findings from these exome sequencing studies can only be translated therapeutically once the functional consequences of these mutations have been determined. Here, we highlight the recent study by An et al. ^[4] which investigated the functional effects of mutations in the SPOP gene that were identified in the aforementioned exome sequencing studies, particularly in the context of SPOP-mediated degradation of the AR.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

A recently published paper addressed the interesting topic of prevention of erectile dysfunction (ED) with tadalafil, a phosphodiesterase-type 5 inhibitor (PDE5i) in patients undergoing radiation therapy for localized prostate cancer. ^[1] Tadalafil 5 mg or placebo was administered once-daily for 24 weeks in patients undergoing external-beam radiotherapy (EBRT) or brachytherapy (BT) for prostate cancer. This randomized trial did not show superior efficacy of the active drug compared with placebo 4-6 weeks after stopping the study drug. Furthermore, patients younger than 65 years did not respond significantly better than older patients.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]

A fundamental question for meiosis is how homologous chromosomes (homologs) find each other and pair together to ensure homologous recombination and segregation. Intuitively, the answer to the question is related to the interaction between homologous sequences. However, that is not the whole story according to some studies on the role of cohesins in homolog pairing. The most recent one by Ishiguro et al.^[1] of the Watanabe group indicates that chromosome architecture defined by a meiosis-specific cohesin protein RAD21L is the key to homology searching. Moreover, they report that homologous pairing is dependent on neither SPO11, an evolutionarily conserved type 2 isomerase responsible for generating DNA double-strand breaks (DSBs), nor SUN1, which tethers the ends of chromosomes to the nuclear envelop (NE) and facilitates chromosome movement and bouquet formation. These discoveries are quite some surprises!

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]