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Abstract: Normal testicular function is dependent upon hormones acting through endocrine and paracrine pathways both in vivo and in vitro. Sertoli cells provide factors necessary for the successful progression of spermatogonia into spermatozoa. Sertoli cells have receptors for follicle stimulating hormone (FSH) and testosterone which are the main hormonal regulators of spermatogenesis. Hormones such as testosterone, FSH and luteinizing hormone (LH) are known to influence the germ cell fate. Their removal induces germ cell apoptosis. Proteins of the Bcl-2 family provide one signaling pathway which appears to be essential for male germ cell homeostasis. In addition to paracrine signals, germ cells also depend upon signals derived from Sertoli by direct membrane contact. Somatostatin is a regulatory peptide playing a role in the regulation of the proliferation of the male gametes. Activin A, follistatin and FSH play a role in germ cell maturation during the period when gonocytes resume mitosis to form the spermatogonial stem cells and differentiating germ cell populations. In vitro cultures systems have provided evidence that spermatogonia in advance stage of differentiation have specific regulatory mechanisms that control their fate. This review article provides an overview of the literature concerning the hormonal pathways regulating spermatogenesis. [Copyright &y& Elsevier]

Abstract: Isolated granulomatous orchitis is a rare chronic testicular inflammation, which should be differentiated from testicular malignancies on scrotal imaging. We present a case of a 33-year-old man, with a diffuse pattern of granulomatous orchitis, confirmed by means of testicular biopsy. MR imaging of the scrotum revealed the presence of two small-sized intratesticular lesions, hypointense on T2-weighted images, not enhancing after gadolinium administration suggesting the diagnosis of benignity. [Copyright &y& Elsevier]

The current study aimed to investigate the sensitivity of male testis parenchyma cells to chemotherapy agents and the protective effects and mechanisms of Morinda citrifolia (Noni) administration against structural and functional changes before and after chemotherapy (Paclitaxel (PTX)). For this purpose, rats were randomly assigned into four groups (Control = G1, PTX 5 mg/kg = G2; PTX + Noni 10 mg/kg = G3, PTX + Noni 20 mg/kg = G4). PTX was injected intraperitoneally for 4 consecutive weeks, at a dose of 5 mg/kg to all groups except the control group. Then noni was administrated in 10 (G3) and 20 (G4) mg/kg groups orally (gavage) for 14 days. Biochemical analyses, Real-Time Polymerase Chain Reaction (PCR), and immunohistochemical analyses were performed. According to our results, Total Oxidative Stress (TOS) and Malondialdehyde (MDA) were significantly increased in the PTX group (P < 0.01). Superoxide Dismutase (SOD) enzyme activity and Total Antioxidant Capacity (TAC) levels were decreased (P < 0.01). The changes in the rats treated with PTX + Noni 20 mg/kg were noteworthy. The increased levels of IL1-β (Interleukin 1 beta) and TNFα (tumor necrosis factor-alpha) with PTX were down-regulated after treatment with PTX + Noni 20 mg/kg (P < 0.01) (9 % and 5 % respectively). In addition, Noni restored the testicular histopathological structure by reducing caspase-3 expression and significantly (61 %) suppressed oxidative DNA damage and apoptosis (by regulating the Bax (bcl-2-like protein 4)/Bcl-2 (B-cell lymphoma gene-2) ratio). In conclusion, Noni reduced cellular apoptosis and drastically changed Caspase 8 and Bax/Bcl-2 levels. Furthermore, it considerably decreases oxidative damage and can be used in testicular degeneration. • PTX-induced toxicity was established in male germ cell Sprague Dawley. • Oxidative stress levels in germ cells and testis tissue were very high. • Noni increased TAC level and decreased SOD and MDA level. • Noni restored the testicular histopathological structure by reducing caspase-3 expression. • Noni significantly (61 %) suppressed oxidative DNA damage and apoptosis by regulating the Bax/Bcl-2 ratio. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the feasibility of testis diffusion tensor imaging (DTI), to determine normative apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values and to assess the efficacy of DTI in characterizing testicular pathology.Materials and Methods: Fifty-six men underwent MRI of the scrotum, including DTI. Parametric and non-parametric statistical tests were used to compare the ADC and FA between the cranial, middle and lower thirds of normal testis and between the bilateral testicular thirds. Comparison between the ADC and FA of normal testis, malignant and benign testicular lesions was performed.Results: No significant differences of the ADC and FA in normal testis between the cranial, middle and lower thirds and between the bilateral testicular thirds were found. ADC was significantly lower in malignancies compared to normal testis (P=0.006) and benign testicular lesions (P=0.006). FA was significantly higher both in malignancies (P=0.001) and benign lesions (P<0.001) compared to normal testis. FA in malignancies did not differ from FA in benign lesions (P=0.221) CONCLUSIONS: This study shows the feasibility of testis DTI. Both ADC and FA significantly differ between testicular lesions and normal testis, although FA did not show an incremental diagnostic value compared to ADC in lesion differentiation. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the difference in apparent diffusion coefficient (ADC) measurements at diffusion-weighted (DW) magnetic resonance imaging of differently shaped regions-of-interest (ROIs) in testicular germ cell neoplasms (TGCNS), the diagnostic ability of differently shaped ROIs in differentiating seminomas from nonseminomatous germ cell neoplasms (NSGCNs) and the interobserver variability.Materials and Methods: Thirty-three TGCNs were retrospectively evaluated. Patients underwent MR examinations, including DWI on a 1.5-T MR system. Two observers measured mean tumor ADCs using four distinct ROI methods: round, square, freehand and multiple small, round ROIs. The interclass correlation coefficient was analyzed to assess interobserver variability. Statistical analysis was used to compare mean ADC measurements among observers, methods and histologic types.Results: All ROI methods showed excellent interobserver agreement, with excellent correlation (P<0.001). Multiple, small ROIs provided the lower mean ADC in TGCNs. Seminomas had lower mean ADC compared to NSGCNs for each ROI method (P<0.001). Round ROI proved the most accurate method in characterizing TGCNS.Conclusion: Interobserver variability in ADC measurement is excellent, irrespective of the ROI shape. Multiple, small round ROIs and round ROI proved the more accurate methods for ADC measurement in the characterization of TGCNs and in the differentiation between seminomas and NSGCNs, respectively. [ABSTRACT FROM AUTHOR]

Introduction The aim of this study is to investigate the role of apparent diffusion coefficient (ADC) values and dynamic contrast enhancement (DCE) patterns in differentiating seminomas from nonseminomatous germ cell tumors (NSGCTs). Materials and methods The MRI examinations of the scrotum of 26 men with histologically proven testicular GCTs were reviewed. DWI was performed in all patients, using a single shot, multi-slice spin-echo planar diffusion pulse sequence and b -values of 0 and 900 s/mm 2 . Subtraction DCE-MRI was performed in 20 cases using a 3D fast-field echo sequence after gadolinium administration. Time-signal intensity curves were created and semi-quantitative parameters (peak enhancement, time to peak, wash-in and wash-out rate) were calculated. The Student's t -test was used to compare the mean values of ADC, peak enhancement, time to peak, wash-in and wash-out rate between seminomas and NSGCTs. ROC analysis was also performed. Results Histopathology disclosed the presence of 15 seminomas and 11 NSGCTs. The mean ± s.d. of ADC values (× 10 −3 mm 2 /s) of seminomas (0.59 ± 0.009) were significantly lower than those of NSGCTs (0.90 ± 0.33) ( P = 0.01). The optimal ADC cut-off value was 0.68 × 10 −3 mm 2 /s. No differences between the two groups were observed for peak enhancement ( P = 0.18), time to peak ( P = 0.63) wash-in rate ( P = 0.32) and wash-out rate ( P = 0.18). Conclusions ADC values may be used to preoperatively differentiate seminomas from NSGCTs. [ABSTRACT FROM AUTHOR]

Introduction The aim of this study is to improve detection of testicular intraepithelial neoplasia (TIN) by measurement of apparent diffusion coefficient (ADC) values. Materials and methods Fifty-six MRI examinations of the scrotum, including 26 histologically proven testicular germ cell neoplasms were retrospectively evaluated. DWI was performed using a single shot, multi-slice spin-echo planar diffusion pulse sequence and b -values of 0 and 900 s mm −2 . ADC measurements were classified into three groups according to their location: group 1 ( n = 19), non-tumoral part, adjacent to testicular carcinoma, where the possible location of TIN was; group 2 ( n = 26), testicular carcinoma; and group 3 ( n = 60), normal testicular parenchyma. Analysis of variance (ANOVA) followed by post hoc analysis (Dunnett T3) was used for statistical purposes. Results The mean ± s.d. of ADC values (×10 −3 mm 2 /s) of different groups were: group 1, 1.08 ± 0.20; group 2, 0.72 ± 0.27; and group 3, 1.11 ± 0.14. ANOVA revealed differences of mean ADC between groups ( F = 38.859, P < 0.001). Post hoc analysis showed differences between groups 2 and 3 ( P < 0.001), groups 2 and 1 ( P < 0.001), but not between groups 3 and 1 ( P = 0.87). Conclusions Based on our preliminary results, ADC values do not provide a reliable differentiation between TIN and testicular carcinoma or normal testicular parenchyma. [ABSTRACT FROM AUTHOR]

The association of sperm nuclear chromatin condensation and ploidy with embryo development and outcome after intra-cytoplasmic sperm injection (ICSI) was explored. The study population consisted of 16 couples referred to loannina University Medical School In vitro Fertilization Unit with male factor infertility and serious impairments in sperm nuclear chromatin condensation and ploidy, according to sperm flow cytometry. Additionally, 20 couples with male factor infertility and relatively high sperm flow cytometry parameters participated as controls. The 35 cycles of the study population were characterized by a lower fertilization rate (P < 0.001 ) as well as decreased grade A embryo rate (P = 0.004) and increased grade C embryo rate (P = 0.028), compared with the 29 cycles of the control group. Additionally, a significantly elevated arrested embryo rate (P < 0.001 ) and a decreased clinical pregnancy rate (P < 0.020) were observed in the couples of the study population. Consequently, high levels of sperm nuclear chromatin condensation abnormalities and sperm aneuploidies are probably associated with lower fertilization rates, impaired embryo quality, elevated arrested embryo rates and decreased pregnancy rates. These preliminary results strongly support the use of sperm flow cytometry as a potential prognostic tool of ICSI outcome. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between the ploidy status and the nuclear chromatin condensation of spermatozoa with conventional semen parameters by using semen flow cytometry (SFC). The prognostic value of SFC on the successful outcome of intrauterine insemination (IUI) was examined. Design: Prospective study. Setting: Patients referred to the IVF Unit of Ioannina University School of Medicine. Patient(s): Ninety-two men with sperm count between 15 × 106 and 40 × 106 spermatozoa/mL and one hundred normozoospermic men were analyzed. Intervention(s): Conventional semen analysis and SFC analysis after acridine orange and propidium iodide staining. IUI performed in 92 couples. Main Outcome Measure(s): Evaluation of sperm maturity and ploidy. Correlation with conventional semen parameters. Result(s): An association of the spermatozoa ploidy status with sperm morphology and motility was revealed. The highest aneuploidy rates were observed when <15% of spermatozoa had normal morphology. An inverse relation was found between sperm morphology and maturity. The pregnancy rates were significantly lower when semen with <15% normal forms (9% vs. 25%), low percentage of mature spermatozoa, and increased total aneuploidy rate were used for IUI. Conclusion(s): Ploidy status and sperm maturity are critical parameters for evaluation of the fertilizing capacity of spermatozoa. SFC could be used to evaluate semen samples before IUI and potentially prognose the outcome. [Copyright &y& Elsevier]

Objective: To understand and delineate the nature and level of DNA damage in association to semen parameters in infertile men. Design: A prospective experimental study. Setting: Alexandroupolis University General Hospital. Patient(s): Eleven fertile and 27 infertile men with various types of infertility. Intervention(s): DNA damage was induced by addition of mitomycin C and caffeine to lymphocyte cultures. Main Outcome Measure(s): Sister chromatid exchange (SCE) levels were assessed in cultures providing a quantitative index of genotoxicity and chromosomal analysis was performed using G-banding and C-banding techniques. Result(s): Karyotyping analysis indicated chromosomal fragility, trisomic lines, and marker chromosomes in some infertile men. Double minute chromosomes were noticed in 11 infertile men and were positively correlated with elevated SCE levels. Necrospermia and varicocele, irrespectively of the degree of severity, were positively correlated with elevated SCE levels. Conclusion(s): Infertile men are prone to have DNA damage; the nature and level of DNA damage varies and is associated with semen parameters. The presence of double minute chromosomes alone is associated with increased double-stranded breaks and abnormal sperm concentration. This study could provide the basis to establish whether and through which process double minute chromosomes could be related to poor semen parameters and regulation of DNA repair. [Copyright &y& Elsevier]

Purpose: To investigate the role of proton magnetic resonance spectroscopy. (1H-MRS) in the assessment of the biochemical environment of testes in infertile men with clinical varicocele.Methods: In this prospective IRB approved study, 13 infertile men with clinical varicocele and 11 age-matched controls were assessed. 1H-MRS was performed using a single voxel point-resolved spectroscopy (PRESS) sequence with TR/TE: 2000/25 ms. Normalized metabolite concentrations, defined as ratios of the calculated metabolite concentrations relative to total creatine (tCr) concentration were compared between infertile testes with clinical varicocele and normal testes using nonparametric statistical tests. Logistic regression analysis was performed to assess the most significant predictor for the diagnosis of varicocele.Results: Several metabolic peaks were found in both infertile testes with clinical varicocele and normal testes. Most prominent peaks were the following: total choline (tCho), tCr, myo-inositol (mI), Glx, and total lipids and macromolecules resonating at 0.9 ppm (TLM09), 1.3 ppm (TLM13) and 2.0 ppm (TLM20). Lower normalized concentrations of tCho (P = 0.001), mI (P = 0.012), Glx (P = 0.011), TLM09 (P = 0.027), TLM13 (P = 0.035) and TLM20 (P = 0.021) were found in infertile testes with clinical varicocele compared with normal men. Total Cho proved the most significant predictor for the diagnosis of clinical varicocele (P = 0.001).Conclusions: 1H-MR spectra of infertile testes with clinical varicocele showed decrease in normalized concentrations of tChol, ml, Glx and lipids. 1H-MRS of the testes might be used as a noninvasive marker of deranged spermatogenesis in infertile men with clinical varicocele. [ABSTRACT FROM AUTHOR]

Objective: To determine factors affecting successful sperm retrieval by testicular sperm extraction in patients with nonmosaic Klinefelter’s syndrome. Design: Medical record analysis for nonmosaic Klinefelter’s syndrome patients who underwent testicular sperm extraction. Setting: Three university-based tertiary centers. Patient(s): Fifty-one patients with nonobstructive azoospermia related to nonmosaic Klinefelter’s syndrome. Intervention(s): Testicular sperm extraction. Main Outcome Measure(s): Correlation of patient characteristics; serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T); as well as testicular volume with success in testicular sperm extraction. Result(s): We succeeded in obtaining spermatozoa in 26 patients and failed in 25. Levels of LH, FSH, and T and testicular volume did not differ between patient groups defined by success and failure. Median ages for successful and failed testicular sperm extraction were 31 and 38 years, respectively (statistically significant difference). When we analyzed success rates of testicular sperm extraction between two patient groups (<35 and ≥35 years old), the percentage of successful recovery of spermatozoa decreased after the age of 35 years (statistically significant difference). Conclusion(s): Testicular sperm extraction should be recommended before the critical age of 35 years. [Copyright &y& Elsevier]