Showing papers in "Asian Journal of Andrology in 2018"
TL;DR: There was a threshold effect among studies investigating FSH and SCOS, and the histopathological findings were helpful to some extent, but all the investigated factors in the study had limited predictive value.
Abstract: We performed this meta-analysis to evaluate the predictive value of different parameters in the sperm retrieval rate (SRR) of microdissection testicular sperm extraction (TESE) in patients with nonobstructive azoospermia (NOA). All relevant studies were searched in PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO. We chose three parameters to perform the meta-analysis: follicle-stimulating hormone (FSH), testicular volume, and testicular histopathological findings which included three patterns: hypospermatogenesis (HS), maturation arrest (MA), and Sertoli-cell-only syndrome (SCOS). If there was a threshold effect, only the area under the summary receiver operating characteristic curve (AUSROC) was calculated. Otherwise, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR) were also calculated. Twenty-one articles were included in our study finally. There was a threshold effect among studies investigating FSH and SCOS. The AUSROCs of FSH, testicular volume, HS, MA, and SCOS were 0.6119, 0.6389, 0.6758, 0.5535, and 0.2763, respectively. The DORs of testicular volume, HS, and MA were 1.98, 16.49, and 1.26, respectively. The sensitivities of them were 0.80, 0.30, and 0.27, while the specificities of them were 0.35, 0.98, and 0.76, respectively. The PLRs of them were 1.49, 10.63, and 1.15, respectively. And NLRs were 0.73, 0.72, and 0.95, respectively. All the investigated factors in our study had limited predictive value. However, the histopathological findings were helpful to some extent. Most patients with HS could get sperm by microdissection TESE.
69 citations
TL;DR: Sperm DNA damage as measured by the SCD appears useful for predicting the clinical pregnancy rate following IVF, and was negatively correlated with IVF outcomes.
Abstract: Sperm DNA damage is recognized as an important biomarker of male infertility. To investigate this, sperm DNA damage was assessed by the sperm chromatin dispersion (SCD) test in semen and motile spermatozoa harvested by combined density gradient centrifugation (DGC) and swim-up in 161 couples undergoing in vitro fertilization (IVF). Semen analysis and sperm DNA damage results were compared between couples who did or did not achieve pregnancy. The sperm DNA damage level was significantly different between the two groups (P < 0.05) and was negatively correlated with IVF outcomes. Logistic regression analysis confirmed that it was an independent predictor for achieving clinical pregnancy. The effects of different levels of sperm DNA damage on IVF outcomes were also compared. There were significant differences in day 3 embryo quality, blastocyst formation rate, and implantation and pregnancy rates (P < 0.05), but not in the basic fertilization rate between the two groups. Thus, sperm DNA damage as measured by the SCD appears useful for predicting the clinical pregnancy rate following IVF.
63 citations
TL;DR: Clinical data are limited which support the use of vitamin D compounds in the management of men with prostate cancer, however, clinical trials guided by existing preclinical data arelimited.
Abstract: Signaling through the vitamin D receptor has been shown to be biologically active and important in a number of preclinical studies in prostate and other cancers. Epidemiologic data also indicate that vitamin D signaling may be important in the cause and prognosis of prostate and other cancers. These data indicate that perturbation of vitamin D signaling may be a target for the prevention and treatment of prostate cancer. Large studies of vitamin D supplementation will be required to determine whether these observations can be translated into prevention strategies. This paper reviews the available data in the use of vitamin D compounds in the treatment of prostate cancer. Clinical data are limited which support the use of vitamin D compounds in the management of men with prostate cancer. However, clinical trials guided by existing preclinical data are limited.
63 citations
TL;DR: A SWOT (strengths, weaknesses, opportunities, and threats) analysis is used to summarize the advantages and drawbacks of Testi-ICSI, and suggests a call for continuous monitoring is nonetheless required concerning the health of generated offspring and the potential complications of sperm retrieval.
Abstract: Spermatozoa retrieved from the testis of men with high levels of sperm DNA fragmentation (SDF) in the neat semen tend to have better DNA quality. Given the negative impact of SDF on the outcomes of Assisted Reproductive Technology (ART), an increased interest has emerged about the use of testicular sperm for intracytoplasmic sperm injection (Testi-ICSI). In this article, we used a SWOT (strengths, weaknesses, opportunities, and threats) analysis to summarize the advantages and drawbacks of this intervention. The rationale of Testi-ICSI is bypass posttesticular DNA fragmentation caused by oxidative stress during sperm transit through the epididymis. Hence, oocyte fertilization by genomically intact testicular spermatozoa may be optimized, thus increasing the chances of creating a normal embryonic genome and the likelihood of achieving a live birth, as recently demonstrated in men with high SDF. However, there is still limited evidence as regards the clinical efficacy of Testi-ICSI, thus creating opportunities for further confirmatory clinical research as well as investigation of Testi-ICSI in clinical scenarios other than high SDF. Furthermore, Testi-ICSI can be compared to other laboratory preparation methods for deselecting sperm with damaged DNA. At present, the available literature supports the use of testicular sperm when performing ICSI in infertile couples whose male partners have posttesticular SDF. Due to inherent risks of sperm retrieval, Testi-ICSI should be offered when less invasive treatments for alleviating DNA damage have failed. A call for continuous monitoring is nonetheless required concerning the health of generated offspring and the potential complications of sperm retrieval.
53 citations
TL;DR: The weight of evidence from long-term epidemiological studies supports a protective effect as evidenced by a reduction in major adverse CV events (MACEs) and mortality in studies which have treated men with testosterone deficiency.
Abstract: Testosterone deficiency is common in men with cardiovascular disease (CVD), and randomized placebo-controlled trials (RCTs) have reported beneficial effects of testosterone therapy on exercise-induced cardiac ischemia in chronic stable angina, functional exercise capacity, maximum oxygen consumption during exercise (VO2max) and muscle strength in chronic heart failure (CHF), shortening of the Q-T interval, and improvement of some cardiovascular risk factors. Testosterone deficiency is associated with an adverse CV risk profile and mortality. Clinical and scientific studies have provided mechanistic evidence to support and explain the findings of the RCTs. Testosterone is a rapid-onset arterial vasodilator within the coronary circulation and other vascular beds including the pulmonary vasculature and can reduce the overall peripheral systemic vascular resistance. Evidence has demonstrated that testosterone mediates this effect on vascular reactivity through calcium channel blockade (L-calcium channel) and stimulates potassium channel opening by direct nongenomic mechanisms. Testosterone also stimulates repolarization of cardiac myocytes by stimulating the ultra-rapid potassium channel-operated current. Testosterone improves cardiac output, functional exercise capacity, VO2maxand vagally mediated arterial baroreceptor cardiac reflex sensitivity in CHF, and other mechanisms. Independent of the benefit of testosterone on cardiac function, testosterone substitution may also increase skeletal muscle glucose metabolism and enhance muscular strength, both factors that could contribute to the improvement in functional exercise capacity may include improved glucose metabolism and muscle strength. Testosterone improves metabolic CV risk factors including body composition, insulin resistance, and hypercholesterolemia by improving both glucose utilization and lipid metabolism by a combination of genomic and nongenomic actions of glucose uptake and utilization expression of the insulin receptor, glucose transporters, and expression on regulatory enzymes of key metabolic pathways. The effect on high-density lipoprotein-cholesterol (HDL-C) differs between studies in that it has been found to fall, rise, or have no change in levels. Testosterone replacement can suppress the levels of circulating pro-inflammatory cytokines and stimulate the production of interleukin-10 (IL-10) which has anti-inflammatory and anti-atherogenic actions in men with CVD. No effect on C-reactive protein has been detected. No adverse effects on clotting factors have been detected. RCTs have not clearly demonstrated any significant evidence that testosterone improves or adversely affects the surrogate markers of atherosclerosis such as reduction in carotid intima thickness or coronary calcium deposition. Any effect of testosterone on prevention or amelioration of atherosclerosis is likely to occur over years as shown in statin therapy trials and not months as used in testosterone RCTs. The weight of evidence from long-term epidemiological studies supports a protective effect as evidenced by a reduction in major adverse CV events (MACEs) and mortality in studies which have treated men with testosterone deficiency. No RCT where testosterone has been replaced to the normal healthy range has reported a significant benefit or adverse effect on MACE nor has any recent meta-analysis.
50 citations
TL;DR: It is suggested that HPV infection of semen was a risk factor for male fertility abnormality with an OR of 3.02, and sensitivity analysis revealed that the results of this study were robust.
Abstract: Human papillomavirus (HPV) is the most common sexually transmitted virus in males and females worldwide; yet its impact upon male fertility remains unclear. The objective of this study was to evaluate the potential impact of HPV infection in semen on male fertility abnormality. A systematic literature search was performed in PubMed, Medline, Embase, Web of Science, and the Cochrane Library database for relevant publications up to May 6, 2017. The odds ratio (OR), and its corresponding 95% confidence interval (CI), was selected to represent the effect size. Statistical analysis was conducted using STATA 12.0. In total, eight articles, providing data on 1955 participants, were included in this meta-analysis. Collectively, the data suggested that HPV infection of semen was a risk factor for male fertility abnormality with an OR of 3.02 (95% CI: 2.11-4.32; I2 = 6.9%). Sensitivity analysis revealed that the results of this study were robust. In conclusion, HPV infection of semen represents a risk factor for male fertility abnormality.
31 citations
TL;DR: Transurethral seminal vesiculoscopy for recurrent hemospermia is an effective and safe procedure in the management of seminal tract disorders and may help other surgeons to become familiar with and improve this procedure.
Abstract: We summarized our experience in transurethral seminal vesiculoscopy (TSV) for recurrent hemospermia by introducing surgical techniques, intraoperative findings, and treatment outcomes. TSV was performed in 419 patients with an initial diagnosis of persistent hemospermia at Shanghai Changhai Hospital (Shanghai, China) from May 2007 to November 2015. TSV was successfully performed in 381 cases (90.9%). Hemospermia was alleviated or disappeared in 324 (85.0%) patients by 3 months after surgery. Common intraoperative manifestations were bleeding, obstruction or stenosis, mucosal lesions, and calculus. Endoscopic presentation of the ejaculatory duct orifice and the verumontanum was categorized into four types, including 8 (1.9%), 32 (7.6%), 341 (81.4%), and 38 (9.1%) cases in Types A, B, C, and D, respectively. TSV is an effective and safe procedure in the management of seminal tract disorders. This study may help other surgeons to become familiar with and improve this procedure. However, further multicentric clinical trials are warranted to validate these findings.
26 citations
TL;DR: Andro increases the sensitivity of PCa cells to TRAIL-induced apoptosis through the generation of ROS and up-regulation of p53 and then promotes PCa cell apoptosis associated with the activation of DR4.
Abstract: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent for anticancer therapy. The identification of small molecules that can establish the sensitivity of prostate cancer (PCa) cells to TRAIL-induced apoptosis is crucial for the targeted treatment of PCa. PC3, DU145, JAC-1, TsuPr1, and LNCaP cells were treated with Andrographolide (Andro) and TRAIL, and the apoptosis was measured using the Annexin V/PI double staining method. Real time-polymerase chain reaction (PCR) and Western blot analysis were performed to measure the expression levels of target molecules. RNA interference technique was used to down-regulate the expression of the target protein. We established a nude mouse xenograft model of PCa, which was used to measure the caspase-3 activity in the tumor cells using flow cytometry. In this research study, our results demonstrated that Andro preferentially increased the sensitivity of PCa cells to TRAIL-induced apoptosis at subtoxic concentrations, and the regulation mechanism was related to the up-regulation of DR4. In addition, it also increased the p53 expression and led to the generation of reactive oxygen species (ROS) in the cells. Further research revealed that the DR4 inhibition, p53 expression, and ROS generation can significantly reduce the apoptosis induced by the combination of TRAIL and Andro in PCa cells. In conclusion, Andro increases the sensitivity of PCa cells to TRAIL-induced apoptosis through the generation of ROS and up-regulation of p53 and then promotes PCa cell apoptosis associated with the activation of DR4.
25 citations
TL;DR: Data show that CHRM1 is involved in the regulation of prostate cancer migration and invasion through the hedgehog signaling pathway.
Abstract: The autonomic nervous system contributes to prostate cancer proliferation and metastasis However, the exact molecular mechanism remains unclear In this study, muscarinic acetylcholine receptor M1 (CHRM1) expression was measured via immunohistochemical analysis in human prostate cancer tissue array slides PC-3, LNCaP, and A549 cells were treated with pirenzepine or carbachol, and the cell migration and invasion abilities were evaluated Western blotting and quantitative real-time PCR were performed to measure GLI family zinc finger 1 (GLI1), patched 1 (PTCH1), and sonic hedgehog (SHH) expression levels High expression of CHRM1 was found in early-stage human prostate cancer tissues In addition, the selective CHRM1 antagonist pirenzepine inhibited PC-3, LNCaP, and A549 cell migration and invasion, but the agonist carbachol promoted the migration and invasion of these three cell lines Muscarinic signaling can be relayed by hedgehog signaling These data show that CHRM1 is involved in the regulation of prostate cancer migration and invasion through the hedgehog signaling pathway
25 citations
TL;DR: To clarify the functions and mechanism of stimulated by retinoic acid gene 8 (Stra8) in spermatogenesis, the testes from Stra8 knockout and wild-type mice during the first wave of sperMatogenesis were analyzed and a preliminary regulatory network of Stra8 was established.
Abstract: To clarify the functions and mechanism of stimulated by retinoic acid gene 8 (Stra8) in spermatogenesis, we analyzed the testes from Stra8 knockout and wild-type mice during the first wave of spermatogenesis. Comparisons showed no significant differences in morphology and number of germ cells at 11 days postpartum, while 21 differentially expressed genes (DEGs) associated with spermatogenesis were identified. We speculate that Stra8 performs many functions in different phases of spermatogenesis, such as establishment of spermatogonial stem cells, spermatogonial proliferation and self-renewal, spermatogonial differentiation and meiosis, through direct or indirect regulation of these DEGs. We therefore established a preliminary regulatory network of Stra8 during spermatogenesis. These results will provide a theoretical basis for further research on the mechanism underlying the role of Stra8 in spermatogenesis.
24 citations
TL;DR: A case of cryptozoospermia is reported in a 33-year-old patient, who sought treatment for primary sterility that had been ongoing for 5 years, and was born of consanguineous parents who were maternal cousins.
Abstract: screening was carried out according to the European Academy of Andrology (EAA) guidelines by real-time fluorescent PCR using the Y Chromosomal Microdeletion Test Kit (Shanghai Tellgen Corporation, Shanghai, China), which detected the sY84 and sY86 sequence-tagged sites (STSs) of azoospermia factor a (AZFa), the sY127 and sY134 STSs of AZFb, and the sY254 and sY255 STSs of AZFc. All six STSs were present, indicating that the patient did not have a Y-chromosome microdeletion. The initial clinical diagnosis was primary infertility with cryptozoospermia, bilateral testicular dysplasia, and high-gonadotropin gonadal-function decline. With the approval of the Ethics Committee of Yantai Yuhuangding Hospital and with the patient’s informed consent, peripheral blood was extracted for exome sequencing. Because the patient’s parents were consanguineous, bioinformatics analysis was performed to identify inheritance of recessive characteristics. All the homozygous mutations were screened to identify potentially pathogenic gene alterations related to spermatogenesis, through phenotype and genotype correlation analysis. A novel nonsense mutation was identified at exon 1:c.6934G>A (p.R2312X) of the testis-expressed 15 (TEX15) gene, which resulted in a truncated TEX15 protein. This mutation was confirmed by Sanger sequencing. Both parents of the proband were carriers of this mutation (Figure 2). We speculated that this mutation was at least in part the cause of the spermatogenic dysfunction. Because of the extremely limited availability of the patient’s spermatozoa, detection of TEX15 mRNA or TEX15 protein in spermatozoa was not possible. Spermatogenesis is a highly complex process of cell differentiation, which is necessary for the formation of haploid spermatozoa. The core of this process is meiosis in spermatocytes, during which synapsis and recombination of homologous chromosomes occur. TEX15 was first identified as a protein that is required for chromosomal synapsis and meiotic recombination in 2008.5 In TEX15-deficient male mice, DNA double-strand breaks (DSBs) are formed and not repaired, suggesting that TEX15 functions in the repair of DSBs via regulation of the loading of DNA repair proteins (RAD51 and DMC1) onto sites of DSBs. Homozygous deletion of TEX15 in mice also leads to significantly reduced testis volume.5 In an analysis of single-nucleotide polymorphisms (SNPs) in TEX15, rs323346 and rs323347 were identified as genetic risk factors for spermatogenic failure in the Chinese Han population.6 In 2015, Okutman and colleagues reported that a nonsense mutation (c.2130T>G, p.Y710X) Dear Editor, Male infertility, which affects approximately 20 million people worldwide, is commonly caused by spermatogenic dysfunctions, including severe oligozoospermia, cryptozoospermia, and nonobstructive azoospermia, which are largely genetic in origin.1–3 Here, we report a case of cryptozoospermia in a 33-year-old patient, who sought treatment for primary sterility that had been ongoing for 5 years. The patient had intercourse with his spouse without contraception two to three times per week, but they had not achieved pregnancy. The patient was born of consanguineous parents who were maternal cousins (Figure 1). He had no history of adverse sexual contact or inappropriate hobbies. He was 161 cm tall and weighed 80 kg, and his external genital organs were normally developed, with both testes around 6 ml in size, and no palpable abnormality in his bilateral spermatic veins. The patient underwent three semen examinations in our hospital and other institutions. In our hospital, the semen analysis was carried out according to the guidelines in the WHO Laboratory Manual for the Examination and Processing of Human Semen.4 The patient’s semen volume was 3.0–3.5 ml, pH 7.2–7.5, and spermatozoa were absent from his semen smear. Semen centrifugal sediment smear showed a sperm count of 0–2 cells per high-power field (HPF), and very few active spermatozoa were observed. Staining with Diff-Quik indicated normal morphology in 2.5%–4.0% of spermatozoa. Sex-hormone levels were follicle-stimulating hormone (FSH) 20.8 mIU ml−1 (reference value 1.5–12.4 mIU ml−1), luteinizing hormone (LH) 10.4 mIU ml−1 (reference value 1.7–8.6 mIU ml−1), testosterone (T) 2.9 ng ml−1 (reference value 2.5–8.4 ng ml−1), estradiol (E2) 40.5 pg ml−1 (reference value 7.6–42.6 pg ml−1), and prolactin (PRL) 5.1 ng ml−1 (reference value 2.6–13.1 ng ml−1). No abnormalities were revealed by peripheral-blood chromosomal-karyotype analysis. Y-chromosome-microdeletion Case study of a patient with cryptozoospermia associated with a recessive TEX15 nonsense mutation
TL;DR: PEDT was valid in the diagnosis of evidenced-based-defined PE and IIEF-15 was negatively related to PEDT in men with different types of PE, and was suggested that a score of ≥9 indicated PE in both LPE and APE.
Abstract: The premature ejaculation diagnostic tool (PEDT) is a brief diagnostic measure to assess premature ejaculation (PE). However, there is insufficient evidence regarding its validity in the new evidence-based-defined PE. This study was performed to evaluate the validity of PEDT and its association with IIEF-15 in different types of evidence-based-defined PE. From June 2015 to January 2016, a total of 260 men complaining of PE and defined as lifelong PE (LPE)/acquired PE (APE) according to the evidence-based definition from Andrology Clinic of the First Affiliated Hospital of Anhui Medical University, along with 104 male healthy controls without PE from a medical examination center, were enrolled in this study. All individuals completed questionnaires including demographics, medical and sexual history, as well as PEDT and IIEF-15. After statistical analysis, it was found that men with PE reported higher PEDT scores (14.28 ± 3.05) and lower IIEF-15 (41.26 ± 8.20) than men without PE (PEDT: 5.32 ± 3.42, IIEF-15: 52.66 ± 6.86, P < 0.001 for both). It was suggested that a score of ≥9 indicated PE in both LPE and APE by sensitivity and specificity analyses (sensitivity: 0.875, 0.913; specificity: 0.865, 0.865, respectively). In addition, IIEF-15 were higher in men with LPE (42.64 ± 8.11) than APE (39.43 ± 7.84, P < 0.001). After adjusting for age, IIEF-15 was negatively related to PEDT in men with LPE (adjust r = -0.225, P < 0.001) and APE (adjust r = -0.378, P < 0.001). In this study, we concluded that PEDT was valid in the diagnosis of evidenced-based-defined PE. Furthermore, IIEF-15 was negatively related to PEDT in men with different types of PE.
TL;DR: Weight loss and treatment to replace testosterone levels improve the metabolic profile and quality of life in patients with obesity and hypogonadism; these beneficial effects depend on treatment modality and duration of therapy.
Abstract: Male hypogonadism associated with obesity is a very prevalent condition and is increasing in parallel with the epidemic prevalence of obesity. Low testosterone levels promote higher fat mass with reduced lean mass. Male hypogonadism is related to an increase in associated cardiometabolic complications, such as hypertension, type 2 diabetes mellitus, the metabolic syndrome, and cardiovascular disease. Its influence as a comorbidity of obesity is becoming more evident and should be evaluated and treated in at-risk patients. Mechanisms involved in this relationship include body composition changes, the presence of adipokines, insulin resistance, and other factors, some of which are still unknown. Weight loss and treatment to replace testosterone levels improve the metabolic profile and quality of life in patients with obesity and hypogonadism; these beneficial effects depend on treatment modality and duration of therapy. The use of testosterone replacement therapy may be indicated, as it has not been shown to increase cardiovascular risk, and retrospective studies suggest a reduction in events in men with metabolic syndrome and type 2 diabetes.
TL;DR: The results showed that ZEB1 could be a key promoter of tumoral progression toward advanced stages of PCa, and expression of Z EB1 regulates epithelial–mesenchymal transition and malignant characteristics in PCa cell lines.
Abstract: It has been reported that one of the factors that promotes tumoral progression is the abnormal activation of the epithelial-mesenchymal transition program. This process is associated with tumoral cells acquiring invasive and malignant properties and has the transcription factor zinc finger E-box-binding homeobox 1 (ZEB1) as one of its main activators. However, the role of ZEB1 in promoting malignancy in prostate cancer (PCa) is still unclear. Here, we report that ZEB1 expression correlates with Gleason score in PCa samples and that expression of ZEB1 regulates epithelial-mesenchymal transition and malignant characteristics in PCa cell lines. The results showed that ZEB1 expression is higher in samples of higher malignancy and that overexpression of ZEB1 was able to induce epithelial-mesenchymal transition by upregulating the mesenchymal marker Vimentin and downregulating the epithelial marker E-Cadherin. On the contrary, ZEB1 silencing repressed Vimentin expression and upregulated E-Cadherin. ZEB1 expression conferred enhanced motility and invasiveness and a higher colony formation capacity to 22Rv1 cells whereas DU145 cells with ZEB1 silencing showed a decrease in those same properties. The results showed that ZEB1 could be a key promoter of tumoral progression toward advanced stages of PCa.
TL;DR: The testes of the adult rats were the most affected by chronic stress, however, the stressed adult rats recovered well from the testicular alterations and could be reversed when stress induction is ended.
Abstract: The objective of this study was to investigate the effects of chronic stress on the testes of prepubertal and adult rats and to evaluate whether any alterations could be reversed when stress induction is ended. Seventy-six male rats were assigned to eight groups depending on the type of treatment (control or stressed), the age at which stress was initiated (prepubertal or adult), and the time of evaluation (immediate or late). Stress stimuli were applied for 6 weeks. Stressed prepubertal and adult rats evaluated immediately after the last stress stimulus were included in SP-I and SA-I groups, respectively. The late prepubertal (SP-L) and adult (SA-L) groups of stressed rats were evaluated 6 weeks after the last stress stimulus. Age-matched rats were used as controls (CP-I, CA-I, CP-L, and CA-L groups). Application of stress stimuli to rats in the SP-I group resulted in body weight and seminiferous tubule diameter reduction. The rats in the SA-I group also showed several functional (testosterone level and sperm parameter) and morphological (testicular weight and seminiferous tubule diameter) reductions. The rats in the SP-L group showed increased body weight and intertubular compartment volumetric and absolute densities and reduced tubular compartment volumetric density. The rats in the SA-L group presented only reduced sperm viability. Stress stimuli promoted changes in the rats in all the study groups. The testes of the adult rats were the most affected by chronic stress. However, the stressed adult rats recovered well from the testicular alterations.
TL;DR: Seminal plasma miR-192a appears to be a potential marker for successfully indicating spermatozoa in the ejaculate following microsurgical varicocelectomy in men with nonobstructive azoospermia andvaricoceles.
Abstract: This study was performed to investigate a potential marker for the presence of spermatozoa in the ejaculate following varicocelectomy in Chinese men with nonobstructive azoospermia and varicoceles. The micro-RNA (miR)-192a levels in seminal plasma and testicular tissue were evaluated by quantitative real-time polymerase chain reaction from 60 men with nonobstructive azoospermia and varicoceles (Group A: 27 men with spermatozoa found in the ejaculate after surgery; Group B: 33 men without spermatozoa found in the ejaculate after surgery) and 30 controls. The seminal plasma and testicular tissue miR-192a levels were higher in Group B than in Group A and the controls (P 0.05). Apoptosis and proliferation assays with miR mimics and inhibitors showed that miR-192a induced GC-2 cell apoptosis through the activation of Caspase-3 protein. Thus, seminal plasma miR-192a appears to be a potential marker for successfully indicating spermatozoa in the ejaculate following microsurgical varicocelectomy in men with nonobstructive azoospermia and varicoceles. Seminal plasma miR-192a may be a useful clinical marker for prescreening to determine which patients with nonobstructive azoospermia and varicoceles would benefit from varicocelectomy.
TL;DR: It is demonstrated that nanotechnology can be used to further improve the effect of small dosage of ADSCs to improve erectile function and is related to the regeneration of the smooth muscle, endothelium, and nerve tissues.
Abstract: Stem cell therapy is a potentially promising option for erectile dysfunction; however, its risk of tumorigenicity is a clinical hurdle and the risk is positively related to the number of injected cells. Our previous study showed that nanotechnology improved adipose-derived stem cell (ADSC) therapy for erectile dysfunction of cavernous nerve injury (CNI) by attracting cells in the corpus cavernosum. These results indicated the possibility of using a reduced dosage of ADSCs for intracavernous injection. In this exploratory study, we used lower dosage (2 × 105 cells) of ADSCs for intracavernous injection (ICI) and the nanotechnology approach. Intracavernous pressure and mean arterial pressure were measured at day 28 to assess erectile function. The low-dose ADSC therapy group showed favorable treatment effects, and nanotechnology further improved these effects. In vivo imaging of ICI cells revealed that the fluorescein signals of NanoShuttle-bound ADSCs (NanoADSCs) were much stronger than those of ADSCs at days 0, 1, and 3. Both immunofluorescence and Western blot analysis showed a significant increase in smooth muscle, endothelium, and nerve tissue in the ADSC group compared to that in the CNI group; further improvement was achieved with assisted nanotechnology. These findings demonstrate that nanotechnology can be used to further improve the effect of small dosage of ADSCs to improve erectile function. Abundant NanoADSCs remain in the corpus cavernosum in vivo for at least 3 days. The mechanism of erectile function improvement may be related to the regeneration of the smooth muscle, endothelium, and nerve tissues.
TL;DR: It was concluded that the PI-RADS v2 could be used as a reliable and independent predictor of PCa and CSPCa and may help in preventing unnecessary invasive procedures.
Abstract: Prostate cancer (PCa) is one of the most common cancers among men globally. The authors aimed to evaluate the ability of the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) to classify men with PCa, clinically significant PCa (CSPCa), or no PCa, especially among those with serum total prostate-specific antigen (tPSA) levels in the "gray zone" (4-10 ng ml-1). A total of 308 patients (355 lesions) were enrolled in this study. Diagnostic efficiency was determined. Univariate and multivariate analyses, receiver operating characteristic curve analysis, and decision curve analysis were performed to determine and compare the predictors of PCa and CSPCa. The results suggested that PI-RADS v2, tPSA, and prostate-specific antigen density (PSAD) were independent predictors of PCa and CSPCa. A PI-RADS v2 score ≥4 provided high negative predictive values (91.39% for PCa and 95.69% for CSPCa). A model of PI-RADS combined with PSA and PSAD helped to define a high-risk group (PI-RADS score = 5 and PSAD ≥0.15 ng ml-1 cm-3, with tPSA in the gray zone, or PI-RADS score ≥4 with high tPSA level) with a detection rate of 96.1% for PCa and 93.0% for CSPCa while a low-risk group with a detection rate of 6.1% for PCa and 2.2% for CSPCa. It was concluded that the PI-RADS v2 could be used as a reliable and independent predictor of PCa and CSPCa. The combination of PI-RADS v2 score with PSA and PSAD could be helpful in the prediction and diagnosis of PCa and CSPCa and, thus, may help in preventing unnecessary invasive procedures.
TL;DR: These age-related values are valuable in evaluating the growth and development status of male external genitalia and could be helpful in diagnosing genital disorders.
Abstract: Genital size is a crucial index for the assessment of male sexual development, as abnormal penile or testicular size may be the earliest visible clinical manifestation of some diseases. However, there is a lack of data regarding penile and testicular size measurements for Chinese boys at all stages of childhood and puberty. This cross-sectional study aimed to develop appropriate growth curves and charts for male external genitalia among children and adolescents aged 0-17 years in Chongqing, China. A total of 2974 boys were enrolled in the present study. Penile length was measured using a rigid ruler, penile diameter was measured using a pachymeter, and testicular volume was determined using a Prader orchidometer. Age-specific percentile curves for penile length, penile diameter, and testicular volume were drawn using the generalized additive models for location, scale, and shape. Very similar growth curves were found for both penile length and penile diameter. Both of them gradually rose to 10 years of age and then sharply increased from 11 to 15 years of age. However, testicular volume changed little before the age of 10 years. This study contributes to the literature covering age-specific growth curve and charts about male external genitalia in Chinese children and adolescents. These age-related values are valuable in evaluating the growth and development status of male external genitalia and could be helpful in diagnosing genital disorders.
TL;DR: A dramatic decline in sperm density was recorded over the first 5 years of study and was reported in Wuhan, Central China, in 2010–2015.
Abstract: The present study aims to analyze sperm concentration trends among young and healthy Chinese adults in Wuhan, Central China, from 2010 to 2015. Semen analysis data from 9357 participants were collected and analyzed using a general linear model and the Cochran-Armitage trend test. A significant decline was observed in sperm concentration (β [standard deviation]: -1.53 [0.16]; P < 0.001). In addition, a decline in sperm density was observed by stratifying student versus nonstudent sperm donors and by analyzing the year of birth or birth year cohort of the participants. Furthermore, the percentage of participants with sperm densities of over 40 × 106 ml-1 significantly decreased with year. Notably, a dramatic decline in sperm density was recorded over the first 5 years of study. This research reported a decline in sperm concentration among young adults in Wuhan, Central China, in 2010-2015.
TL;DR: Novel epithelial cell-derived miRNAs that may regulate the expression of important gene networks that are responsible for the regionalized gene expression and function of the epididymis are shown.
Abstract: The epithelium of the human epididymis maintains an appropriate luminal environment for sperm maturation that is essential for male fertility. Regional expression of small noncoding RNAs such as microRNAs contributes to segment-specific gene expression and differentiated functions. MicroRNA profiles were reported in human epididymal tissues but not specifically in the epithelial cells derived from those regions. Here, we reveal miRNA signatures of primary cultures of caput, corpus, and cauda epididymis epithelial cells and of the tissues from which they were derived. We identify 324 epithelial cell-derived microRNAs and 259 tissue-derived microRNAs in the epididymis, some of which displayed regionalized expression patterns in cells and/or tissues. Caput cell-enriched miRNAs included miR-573 and miR-155. Cauda cell-enriched miRNAs included miR-1204 and miR-770. Next, we determined the gene ontology pathways associated with in silico predicted target genes of the differentially expressed miRNAs. The effect of androgen receptor stimulation on miRNA expression was also investigated. These data show novel epithelial cell-derived miRNAs that may regulate the expression of important gene networks that are responsible for the regionalized gene expression and function of the epididymis.
TL;DR: Peroxynitrite-mediated nitrosative stress induces the regulated variant of cell death known as MPT-driven necrosis in human spermatozoa and opens up a new focus for developing specific therapeutic strategies to better preserve sperm viability or to avoid cell death.
Abstract: Peroxynitrite is a highly reactive nitrogen species and a potent inducer of apoptosis and necrosis in somatic cells. Peroxynitrite-induced nitrosative stress has emerged as a major cause of impaired sperm function; however, its ability to trigger cell death has not been described in human spermatozoa. The objective here was to characterize biochemical and morphological features of cell death induced by peroxynitrite-mediated nitrosative stress in human spermatozoa. For this, spermatozoa were incubated with and without (untreated control) 3-morpholinosydnonimine (SIN-1), in order to generate peroxynitrite. Sperm viability, mitochondrial permeability transition (MPT), externalization of phosphatidylserine, DNA oxidation and fragmentation, caspase activation, tyrosine nitration, and sperm ultrastructure were analyzed. The results showed that at 24 h of incubation with SIN-1, the sperm viability was significantly reduced compared to untreated control (P < 0.001). Furthermore, the MPT was induced (P < 0.01) and increment in DNA oxidation (P < 0.01), DNA fragmentation (P < 0.01), tyrosine nitration (P < 0.0001) and ultrastructural damage were observed when compared to untreated control. Caspase activation was not evidenced, and although phosphatidylserine externalization increased compared to untreated control (P < 0.001), this process was observed in <10% of the cells and the gradual loss of viability was not characterized by an important increase in this parameter. In conclusion, peroxynitrite-mediated nitrosative stress induces the regulated variant of cell death known as MPT-driven necrosis in human spermatozoa. This study provides a new insight into the pathophysiology of nitrosative stress in human spermatozoa and opens up a new focus for developing specific therapeutic strategies to better preserve sperm viability or to avoid cell death.
TL;DR: The study provides preliminary evidence on bilateral intervention in testes in the rituximab era and validates common prognostic factors for Chinese PTL patients.
Abstract: This study aims to investigate the effect of different local testicular treatments and validate common prognostic factors on primary testicular lymphoma (PTL) patients We retrospectively reviewed the clinical records of 32 patients from 1993 to 2017 diagnosed with PTL and included 22 patients for analysis The Kaplan–Meier method, Log-rank test, and multivariate Cox proportional hazard regression analysis were applied to evaluate progression-free survival (PFS), overall survival (OS), and determine prognosis predictors The median follow-up time was 30 months Median OS and PFS were 96 months and 49 months, respectively In univariate analysis, advanced Ann Arbor stage (III/IV) (P
TL;DR: A novel technique utilizing a ventral incision to perform the PP implantation and a double-dorsal patch graft, or “sliding technique” (ST), in patients with severe Peyronie's disease is described.
Abstract: A circumcising incision to deglove the penis for penile prosthesis (PP) implantation can increase the risk of ischemic injury to the glans penis. In order to avoid vascular complications, we describe a novel technique utilizing a ventral incision to perform the PP implantation and a double-dorsal patch graft, or “sliding technique” (ST), in patients with severe Peyronie's disease (PD). Three patients with severe PD and erectile dysfunction at our institution underwent ST and PP implantation through a ventral incision. This new approach was not only successful in facilitating the ST and PP implantation in these patients but also allowed for adequate exposure of the penile shaft with no reported loss of sensation. We also conducted a review of current literature regarding the approaches for PD. While ischemic complications of PP implantation and ST are rare, there are reports of ischemic injury in patients undergoing a circumcising incision. The combination of a circumcising incision and a patient's underlying peripheral artery disease potentially raises a patient's risk of this rare complication. Our innovative ventral incision provides an alternative method for PP implantation and ST in order to avoid ischemia of the penis, while still allowing for adequate exposure.
TL;DR: In men over 55 years old, SCI decreases the prostate cancer risk up to 65.0% than that in controls, which confirms its poor reliability as a screening tool for prostate cancer in SCI.
Abstract: A lower risk of prostate cancer has been reported in men with spinal cord injury (SCI) as compared to that observed in able-bodied subjects. As injury-related consequences can have opposite effects on prostate pathophysiology, this meta-analysis aimed to (1) establish the existence/quantify the extent of decreased prostate cancer risk following SCI and (2) find out if there is any statistically significant difference in prostate-specific antigen (PSA) levels between SCI and able-bodied subjects. MEDLINE, Cochrane Library, Scopus, CINAHL, and ScienceDirect databases were used. Only studies reporting a prostate cancer diagnosis and/or PSA levels following SCI and in able-bodied controls were included. Five studies provided information about prostate cancer on 35 293 subjects with SCI and 158 140 controls. Six studies were included in PSA analysis which reported information on 391 men with SCI and 1921 controls. Pooled estimates indicated that SCI reduced the prostate cancer risk by approximately 50% as compared to controls, whereas differences in PSA levels were not statistically significant. Funnel plots suggested the presence of publication bias only in PSA analysis. Between-study heterogeneity was established and when, according to meta-regression models, analysis was restricted to studies including men with mean age over 55 years, prostate cancer risk in SCI decreased up to 65.0% than that in controls with no heterogeneity (P = 0.33, I2 = 9%). In conclusion, in men over 55 years old, SCI decreases the prostate cancer risk up to 65.0% than that in controls. The large between-study heterogeneity on PSA confirms its poor reliability as a screening tool for prostate cancer in SCI.
TL;DR: It was shown that men who presented isolated chronic epididymitis were more likely to have high percentages of low sperm motility and abnormal sperm morphology as well as a high number of white blood cells.
Abstract: Chronic epididymitis and varicocele are frequently observed genital disorders in men consulting for couple infertility, but their impact on semen characteristics at the time of infertility consultation is still a matter of debate. We investigated 652 male partners of couples who had their first infertility consultation between 1999 and 2015 in Argentina. Men with chronic epididymitis (n = 253), Grade III varicocele (n = 106), and both conditions (n = 125) were compared with a control group (n = 168) composed of men without these disorders or any other recognized causes of male infertility. We showed that men who presented isolated chronic epididymitis were more likely to have high percentages of low sperm motility and abnormal sperm morphology as well as a high number of white blood cells. Men with isolated Grade III varicocele had low sperm production and motility and an increased percentage of abnormal sperm morphology. Finally, men who simultaneously presented chronic epididymitis with Grade III varicocele had a low sperm motility and increased percentage of abnormal sperm morphology as well as a high number of white blood cells. Physical examination of the genital organs may identify common disorders, potentially involved as causal factors of patient's infertility. These disorders are associated with specific seminal profiles that should help in identifying the best treatment from the available therapeutic options, effectiveness, safety, and allowing as much as possible natural conception.
TL;DR: It is proposed that testicular angiotensin-converting enzyme could be used to aid embryologists in selecting better semen samples for obtaining high-quality blastocysts during in vitro fertilization procedures.
Abstract: Angiotensin-converting enzyme functions in the male reproductive system, but the extent of its function in reproduction is not fully understood. The primary objective of this work was to investigate the relationship between the testicular isoform of angiotensin-converting enzyme present in human spermatozoa and semen parameters, human embryo quality, and assisted reproduction success. A total of 81 semen samples and 635 embryos from couples undergoing oocyte donation cycles at the IVI Bilbao Clinic were analyzed. Semen parameters, embryos quality, and blastocyst development were examined according to the World Health Organization standards and the Spanish Association of Reproduction Biology Studies criteria. The percentage of testicular angiotensin-converting enzyme-positive spermatozoa and the number of molecules per spermatozoon were analyzed by flow cytometry. Both parameters were inversely correlated with human sperm motility. Higher percentages of testicular angiotensin-converting enzyme-positive spermatozoa together with fewer enzyme molecules per spermatozoon were positively correlated with better embryo quality and development. Our results suggest that embryos with a higher implantation potential come from semen samples with higher percentages of testicular angiotensin-converting enzyme-positive cells and fewer enzyme molecules per spermatozoon. Based on these findings, we propose that testicular angiotensin-converting enzyme could be used to aid embryologists in selecting better semen samples for obtaining high-quality blastocysts during in vitro fertilization procedures.
TL;DR: The data suggest that the inhibition of LimK2, particularly with administration of 10.0 mg kg−1 body weight LIMK2i, can improve corporal fibrosis and erectile function by normalizing the LIMK 2/Cofilin pathway.
Abstract: We evaluated whether LIM-kinase 2 inhibitor (LIMK2i) could improve erectile function by suppressing corporal fibrosis through the normalization of the Rho-associated coiled-coil protein kinase 1 (ROCK1)/LIMK2/Cofilin pathway in a rat model of cavernous nerve crush injury (CNCI). Sixty 11-week-old male Sprague-Dawley rats were divided equally into five groups: sham surgery (S), CNCI (I), and CNCI treated with low-dose (L), medium-dose (M), and high-dose (H) LIMK2i. The L, M, and H groups were treated with a daily intraperitoneal injection of LIMK2i (2.5, 5.0, and 10.0 mg kg-1 body weight, respectively) for 1 week after surgery. The erectile response was assessed using electrostimulation at 1 week, postoperatively. Penile tissues were processed for Masson's trichrome staining, double immunofluorescence, and Western blot assay. Erectile responses in the H group improved compared with the I group, while the M group showed only partial improvement. A significantly decreased smooth muscle/collagen ratio and an increased content of fibroblasts positive for phospho-LIMK2 were noted in the I group. The M and H groups revealed significant improvements in histological alterations and the dysregulated LIMK2/Cofilin pathway, except for LIMK2 phosphorylation in the M group. The inhibition of LIMK2 did not affect the ROCK1 protein expression. The content of fibroblasts positive for phospho-LIMK2 in the H group returned to the level found in the S group, whereas it did not in the M group. However, the L group did not exhibit such improvements. Our data suggest that the inhibition of LIMK2, particularly with administration of 10.0 mg kg-1 body weight LIMK2i, can improve corporal fibrosis and erectile function by normalizing the LIMK2/Cofilin pathway.
TL;DR: Sipuleucel-T demonstrated a survival benefit in this population, indicating that prostate cancer is an immunoresponsive disease; however, these results have not been matched by other agents.
Abstract: Despite impressive survival benefits with immunotherapy in patients with various solid tumors, the full potential of these agents in prostate cancer has yet to be realized. Sipuleucel-T demonstrated a survival benefit in this population, indicating that prostate cancer is an immunoresponsive disease; however, these results have not been matched by other agents. A large trial with ipilimumab in prostate cancer failed to meet its primary objective, and small trials with PD-1/PD-L1 inhibitors did not yield a significant improvement in overall response. However, several late-stage clinical trials are underway with other vaccines in prostate cancer. Reports of clinical benefit with immunotherapies, particularly when used in combination or a select population, have provided the framework to develop sound clinical trials. Understanding immunogenic modulation, antigen spread, biomarkers, and DNA-repair defects will also help mold future strategies. Through rational patient selection and evidence-based combination approaches, patients with prostate cancer may soon derive durable survival benefits with immunotherapies.
TL;DR: The PSA-AV score performed equally with PSAD and was better than PSA in predicting PCa in a Chinese biopsy population, indicating that PSA -AV score could be a useful tool for predicting prostate cancer in Chinese population.
Abstract: This study was performed to evaluate prostate-specific antigen-age volume (PSA-AV) scores in predicting prostate cancer (PCa) in a Chinese biopsy population. A total of 2355 men who underwent initial prostate biopsy from January 2006 to November 2015 in Huashan Hospital were recruited in the current study. The PSA-AV scores were calculated and assessed together with PSA and PSA density (PSAD) retrospectively. Among 2133 patients included in the analysis, 947 (44.4%) were diagnosed with PCa. The mean age, PSA, and positive rates of digital rectal examination result and transrectal ultrasound result were statistically higher in men diagnosed with PCa (all P < 0.05). The values of area under the receiver operating characteristic curves (AUCs) of PSAD and PSA-AV were 0.864 and 0.851, respectively, in predicting PCa in the entire population, both performed better than PSA (AUC = 0.805; P < 0.05). The superiority of PSAD and PSA-AV was more obvious in subgroup with PSA ranging from 2.0 ng ml-1 to 20.0 ng ml-1. A PSA-AV score of 400 had a sensitivity and specificity of 93.7% and 40.0%, respectively. In conclusion, the PSA-AV score performed equally with PSAD and was better than PSA in predicting PCa. This indicated that PSA-AV score could be a useful tool for predicting PCa in Chinese population.