Bi-allelic Mutations in M1AP Are a Frequent Cause of Meiotic Arrest and Severely Impaired Spermatogenesis Leading to Male Infertility.

Male infertility affects ∼7% of men, but its causes remain poorly understood. The most severe form is non-obstructive azoospermia (NOA), which is, in part, caused by an arrest at meiosis. So far, only a few validated disease-associated genes have been reported. To address this gap, we performed whole-exome sequencing in 58 men with unexplained meiotic arrest and identified the same homozygous frameshift variant c.676dup (p.Trp226LeufsTer4) in M1AP, encoding meiosis 1 associated protein, in three unrelated men. This variant most likely results in a truncated protein as shown in vitro by heterologous expression of mutant M1AP. Next, we screened four large cohorts of infertile men and identified three additional individuals carrying homozygous c.676dup and three carrying combinations of this and other likely causal variants in M1AP. Moreover, a homozygous missense variant, c.1166C>T (p.Pro389Leu), segregated with infertility in five men from a consanguineous Turkish family. The common phenotype between all affected men was NOA, but occasionally spermatids and rarely a few spermatozoa in the semen were observed. A similar phenotype has been described for mice with disruption of M1ap. Collectively, these findings demonstrate that mutations in M1AP are a relatively frequent cause of autosomal recessive severe spermatogenic failure and male infertility with strong clinical validity.

Semen reactive oxygen species levels are correlated with erectile function among chronic prostatitis/chronic pelvic pain syndrome patients.

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is often associated with erectile dysfunction (ED). However, the underlying pathophysiological mechanisms of ED occurrence are still unclear in patients with CP/CPPS. The aim of the study was to investigate superoxide anion (O2•-) and total reactive oxygen species (ROS) production in semen of men with category IIIA CP/CPPS and their association with ED. This prospective study included 33 men with category IIIA CP/CPPS. Control group consisted of 13 healthy men. Total ROS and O2•- production were assayed by luminol and lucigenin-dependent chemiluminescence (CL) methods, respectively. ED was evaluated using the IIEF-5 questionnaire. Patients with CP/CPPS had significantly higher seminal total ROS and O2•- levels than healthy control subjects (2.9 ± 0.5 relative light unit (RLU) vs. 2.4 ± 0.2 RLU, p < 0.001; luminol-dependent CL and 2.5 ± 0.4 RLU vs. 2.3 ± 0.2 RLU, p = 0.02; lucigenin-dependent CL, respectively). Seminal O2•- and ROS levels were negatively correlated with IIEF-5 scores (r = -0.556, r = -0.536; p < 0.001, respectively). These results may suggest O2•-/ROS overproduction could be one of the important mechanisms in the etiology of ED development in CP/CPPS patients.

Prevalence of sexual dysfunction and urinary incontinence and associated risk factors in Turkish women.

OBJECTIVES: Female sexual dysfunction (FSD) and urinary incontinence (UI) are associated risk factors that might cause each other. No study has investigated prevalence of FSD and UI in the same population. The aims of the study were to investigate the prevalence of FSD and UI and associated risk factors in the same population. STUDY DESIGN: The study included 1217 women in 20 provinces, representing the geographical regions of Turkey. Women aged ≥18 years with active sexual life in the last 6 months were enrolled. FSD, overactive bladder, UI, depression, and sexual distress were investigated using validated scales. Risk factors that might predict FSD and UI were determined in the same population. RESULTS: The prevalence of FSD and UI was 52.5% and 14.6%, respectively. Comparing the women with and without FSD, those with FSD were older, had higher body mass index (BMI), less physical exercise, older spouses, lower educational level, and lower rates of smoking and alcohol consumption. The rates of women in menopause and those with a spouse/partner having erection problem and the rates of UI, depression, and sexual distress were higher in the FSD group. Age of spouse, low educational level, not smoking, not consuming alcohol, menopause, not giving consent to spouse/partner to use sexual performance-enhancing drugs when necessary, depression, and sexual distress were the significant risk factors for FSD. Of the women with UI, 56% had overactive bladder symptoms, 32% had stress UI, and 12% had mixed type UI. Comparing the women with and without UI, those with UI were older, had higher BMI, lower educational level, and older spouses. The rate of menopausal women and the rates of FSD, depression, and sexual distress were higher in the UI group. Menopause and FSD were the significant risk factors for UI. CONCLUSIONS: This is the first study to investigate prevalence of FSD and UI in the same population. UI deteriorates sexual functions of women. Therefore, both conditions should be assessed when women complain of either sexual or urinary problems.

Apoptosis in testicular tissue of rats after vasectomy: evaluation of eNOS, iNOS immunoreactivities and the effects of ozone therapy.

OBJECTIVE: We aimed to investigate the changes in endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) expression and apoptotic index in rat testicular tissue, as well as serum and seminal plasma sex hormone levels after vasectomy, and the effect of ozone therapy (OT). MATERIAL AND METHODS: Adult male Wistar rats were used (n=6 per group). Control (G1), sham for 4 weeks (G2) or 6 weeks (G3), orchiectomy at the 4(th) (G4) or 6(th) (G5) week after left vasectomy, orchiectomy at the 4(th) (G6) or 6(th) (G7) week after bilateral vasectomy, orchiectomy after 6 weeks OT following left (G8) or bilateral (G9) vasectomy, orchiectomy after 6 weeks OT (G10). RESULTS: In the left testes, while there were increases in eNOS and iNOS immunoreactivity and apoptotic indexes in G4 and G5, no changes were observed in contralateral testis. These values increased in G6 and G7, while OT inhibited these parameters in the left testis of G8 and both testes of G9. Sex hormone levels did not show any changes after vasectomy and ozone therapy. CONCLUSION: While OT was found to be protective against some parameters mentioned above under stress conditions, it seemed to cause some harmful effects when used in healthy conditions.

Orexin expression in different prostate histopathologic examinations: Can it be a marker for prostate cancer? A preliminary result.

OBJECTIVE: The aim of this study was to evaluate the expression of the orexin receptor in different prostate pathologies, including prostate adenocarcinoma, benign prostate hyperplasia and chronic prostatitis. MATERIAL AND METHODS: A total of 90 patients (mean age 64.01±7.2 years) were enrolled in the study. The patients were divided into three groups of equal numbers based on their histopathologic findings: prostate cancer (Group 1), benign prostate hyperplasia (Group 2) and chronic prostatitis (Group 3). All the tissues were incubated with a primary antibody recognizing the Orexin receptor. The specific cytoplasmic immunoreactivity of the Orexin receptor was semiquantitatively scored for intensity and distribution based on a grading scale. The staining intensity and orexin expression were evaluated using Pearson χ(2) test. RESULTS: A heterogeneous staining pattern of the Orexin receptor was observed between the groups. The expression rates were 90% (27/30) in Group 1, 53.3% (16/30) in Group 2 and 26.7% (8/30) in Group 3. While 5 patients (9.3%) in Group 1 showed strong staining, all samples from the other 2 groups showed only weak staining. There were significant differences in staining intensity between the three groups. The expression and distribution of the Orexin receptor was more widespread in Group 1 than in the other groups and was higher in patients with poorly differentiated malignancy. However, there was no significant difference based on Gleason score. CONCLUSION: Orexin receptors are found in human prostate tissues and their expression is widespread in prostate cancer and in patients with a higher Gleason score. Therefore, we believe that Orexin immunoreactivity can be considered to be an indicator of poor prognosis and of poorly differentiated prostate cancer cases.

Citrate levels in fresh tomato juice: a possible dietary alternative to traditional citrate supplementation in stone-forming patients.

OBJECTIVES: To detect citrate levels in fresh tomato juice, to reveal whether it can be studied for prevention of recurrent hypocitraturic nephrolithiasis. METHODS: Juices of tomato, orange, lemon, and mandarin were extracted and blended with a hand blender, and 10 samples of 100 mL were taken from each. Citrate, oxalate, calcium, phosphorus, magnesium, sodium, potassium, chloride, and pH levels were examined in these. The same variables were re-evaluated after the samples were stored at +4 degrees C for 1 week. RESULTS: In fresh tomato juice, higher citrate and magnesium levels as well as lower sodium and oxalate levels were detected as compared with the other juices. No differences were observed with regard to all variables among fresh orange, lemon, and mandarin juices. The level of citrate in the fresh tomato juice was higher at a statistically significant level than that in tomato juice that was stored for 1 week. The amount of oxalate increased in stored tomato juice. CONCLUSIONS: Fresh tomato juice is considered a rich source of citrate. Furthermore, a high level of magnesium and a low level of sodium and oxalate content were detected in fresh tomato juice, the usability of which in recurrent hypocitraturic nephrolithiasis can be investigated in clinical studies.

Can prilocaine infiltration alone be the most minimally invasive approach in terms of anesthesia during extracorporeal shock wave lithotripsy?

OBJECTIVES: To evaluate the analgesic effect and utility of prilocaine infiltration alone for minimal morbidity during extracorporeal shock wave lithotripsy. METHODS: A total of 114 patients with kidney stones, aged 18 to 69 years, were randomly separated into two groups. The 58 patients in group 1 received intramuscular diclophenac 30 minutes before extracorporeal shock wave lithotripsy, and the 56 patients in group 2 received prilocaine infiltration into the 30 cm2 area below the 12th rib right before the session. A visual analog scale (0 to 100 mm) was used to evaluate pain. RESULTS: The visual analog scale scores for group 2 were statistically lower at 1, 10, and 20 minutes compared with the scores for group 1 (P = 0.006, P = 0.005, and P = 0.006, respectively). However, no difference was detected at the end of the procedure. The requirement for additional analgesic was less in group 2 (P = 0.007). CONCLUSIONS: Prilocaine infiltration alone can be used for analgesic purposes efficiently and safely during extracorporeal shock wave lithotripsy with minimal morbidity.

Optimal frequency in extracorporeal shock wave lithotripsy: prospective randomized study.

OBJECTIVES: To determine the optimal frequency of extracorporeal shock wave lithotripsy of urolithiasis, in terms of efficacy and duration, by comparing three different shock wave frequencies. METHODS: A total of 170 patients between the ages of 18 and 69 years with radiopaque kidney stones were included in the study. The patients were randomly separated into three groups. Group 1 (56 patients) received 120 shock waves per minute, group 2 (57 patients) received 90 shock waves per minute, and group 3 (57 patients) received 60 shock waves per minute. The duration, analgesic or sedative requirement, and complications were recorded for each treatment. All patients were evaluated in terms of successful treatment by radiography of the kidneys, ureters, and bladder and abdominal ultrasonography 10 days after the single-session therapy. RESULTS: No statistically significant difference was observed in patients according to age, sex, stone size, side, composition, location in the kidney, total energy level, or number of shocks. The successful therapy rate in groups 2 and 3 was prominently greater compared with that for group 1, and the difference was statistically significant (P = 0.032 between groups 1 and 2 and P = 0.015 between groups 1 and 3). The analgesic or sedative requirement in groups 2 and 3 was lower than that in group 1, and the difference was statistically significant (P = 0.003 between groups 1 and 2 and P = 0.001 between groups 1 and 3). The duration was longer in group 3 than in groups 1 and 2, and the difference was statistically significant (P = 0.000 between groups 1 and 3 and P = 0.009 between groups 2 and 3). CONCLUSIONS: The results of our study have shown that the optimal frequency during extracorporeal shock wave lithotripsy is 90 shock waves per minute in terms of duration, efficacy, and analgesic and sedative requirement at the same total energy level.