Andrologia

Exposure to arsenic is linked to a wide range of diseases, in particular male reproductive toxicities. Trametes versicolor is a traditional medicinal fungus with a remarkable potential for antioxidant activity. The purpose of this study was to examine the ameliorating effects of water and methanol extracts of T. versicolor on arsenic-induced male reproductive toxicities via the abrogation of oxidative stress. The mice were divided as follows: control: normal saline, As: arsenic (15 mg/kg), WE: water extract (400 mg/kg), ME: methanol extract (400 mg/kg), As + WE: arsenic (15 mg/kg) + water extract (100, 200, 400 mg/kg), As + ME: arsenic (15 mg/kg) + methanol extract (100, 200, 400 mg/kg), and positive control: arsenic (15 mg/kg) + vitamin C (500 mg/kg). Animals were treated via the intraperitoneal route. About 24 hr later, the mice were euthanized, and oxidative stress parameters (reactive oxygen species [ROS], lipid peroxidation, glutathione concentration, protein carbonylation, glutathione peroxidase, and superoxide dismutase activity), histopathological changes and sperm parameters (count, motility, and morphology) were examined in the testicular tissue. Arsenic caused significant pathological changes in the testicular tissue and sperm morphology and significantly reduced sperm count and motility. Moreover, arsenic mediated oxidative stress via significant increases in ROS generation, lipid peroxidation, and protein carbonyl content, as well as significant depletion in glutathione concentration and superoxide dismutase and glutathione peroxidase activities. Although, coadministration of water and methanol extracts of T. versicolor at 200 and 400 mg/kg counteracted arsenic-induced oxidative and histopathological damages and improved sperm parameters. Our study indicated that T. versicolor ameliorated arsenic-induced testis toxicity and sperm dysfunction via attenuation of oxidative damage.

Several anticancer drugs are coadministered with ascorbate (ASCB) to complement their cytotoxic effects. However, it is not known if the treatment regimen prevents collateral oxidative damage to non-target sites. The current study evaluated the effect of ASCB cotreatment on the testes of young adult rats treated with an anticancer drug, busulfan (BUS). About 40 Wistar rats were arbitrarily assigned into four groups (N = 10), namely, control (<0.2% dimethyl sulfoxide vehicle), BUS (4 mg/kg b.w.; intraperitoneally for 4 days), BUS + ASCB (4 mg BUS/kg b.w. for 4 days + 100 mg ASCB/kg b.w.; intraperitoneally for 14 days and 7 days prior to start of BUS injection), and ASCB (100 mg/kg b.w.; intraperitoneally for 21 days). At the end of study, ASCB + BUS cotreatment reduced spermatogenesis score index, superoxide dismutase activity, total ASCB and decreased hydrogen peroxide level, and elevated catalase activity and nitrite concentration much more than treatment with BUS alone (). Other observations included elevated malondialdehyde level, DNA damage, and diminished glutathione concentration in the testes of BUS + ASCB animals. Interestingly, ASCB administration raised testicular ASCB concentration beyond the control values () and the antioxidant status of the testes. Histological aberrations included many single layers of germ cells, shrinked tubules, and vacuolated structures in the epithelium of BUS + ASCB, similar to those of BUS-treated animals. In conclusion, BUS treatment deregulated the redox status of the testes and caused a dramatic consumption of ASCB which were enhanced by exogenous ASCB resulting to testicular damage.

Calcium ion enters the sperm through a specific calcium channel, CatSper. This voltage-sensitive channel is stimulated by intracellular alkalization and progesterone. This study is aimed at investigating the effects of CatSper inhibition or stimulation on sperm motility, viability, and sperm function regulators such as mitochondrial membrane potential (MMP), ATP, and reactive oxygen species (ROS) production. This study was performed on 30 semen samples of fertile volunteers, referred to Shiraz Fertility Center. The semen samples were diluted to sperm/mL. The samples were divided randomly into control, solvent, progesterone (10 μM), NNC (2 μM), and NNC+progesterone groups. Sperm kinematics, viability, MMP, ATP content, and the amount of ROS production were assessed using VT-SPERM3.1, eosin staining, JC1 flow cytometry, bioluminescence, and chemiluminescence methods, respectively. Sperm viability and total and progressive motility were significantly decreased in the NNC and NNC+progesterone groups. The amplitude of lateral head displacement (ALH) and curvilinear velocity (VCL) was reduced in the NNC-containing groups. These parameters did not change in the progesterone group. ROS production by viable spermatozoa in the NNC and NNC+progesterone groups was significantly higher than the controls. MMP and ATP content did not show any significant difference with controls in none of the experimental groups. NNC inhibits the CatSper and reduces human sperm motility and viability. These harmful NNC effects were not due to their impact on MMP or ATP production but are likely because of intracellular calcium reduction and higher ROS production. Progesterone at 10 μM concentration had no significant effect and may not be a considerable stimulator for CatSper.

Ischemia–reperfusion injury (IRI) after testicular torsion is linked to significant damage in testicular tissue. Dimethyl fumarate (DMF) activates the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, thereby inducing antioxidant and anti-inflammatory effects. We analyzed the usefulness of DMF in preventing IRI following testicular torsion/detorsion in Sprague-Dawley rats (). The animals were classified into control (sham), DMF (200 mg/kg/day), IRI, and IRI+DMF (IRI with 200 mg/kg/day DMF) groups. Testicular IRI was induced by detorsion after 1.5 h of torsion. DMF was administered via oral gavage daily from 1 h before testicular detorsion until day 7, when orchiectomy was performed. The testis-to-body weight ratio was calculated. Histopathological evaluation was performed using the Johnsen and Cosentino scores for seminiferous tubules. Malondialdehyde, superoxide dismutase, and total glutathione levels were determined in testicular tissues. Moreover, Nrf2, heme oxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), nuclear factor kappa B (NF-κB), and inflammatory cytokine (interleukin 1b (IL1b), IL6, and tumor necrosis factor alpha (TNF-α)) levels were determined through quantitative polymerase chain reaction. Nuclear Nrf2 and cytoplasmic HO-1 and NQO1 protein levels were also evaluated. DMF significantly improved the testis-to-body weight ratio and reduced histopathological damage in the testes. Moreover, it significantly improved the concentration of malondialdehyde, superoxide dismutase, and total glutathione. Furthermore, it inhibited NF-κB and inflammatory cytokine mRNA expression compared with the findings obtained in untreated rats with IRI (all ). Nrf2, HO-1, and NQO1 expressions (mRNA and protein) were markedly elevated following DMF treatment in rats with IRI (all ). DMF administration activated the Nrf2 signaling pathway and induced antioxidant and anti-inflammatory effects, thereby improving IRI-induced testicular damage. Thus, DMF may prevent IRI following testicular torsion.

Background. Previously published predictive models for microdissection testicular sperm extraction (micro-TESE) were generally assumed patients with nonobstructive azoospermia (NOA) a homogenous population, i.e., the laboratory predictors were associated with sperm retrieval rate (SRR) in a similar way among different subpopulations. In addition, previous studies primarily regarded the success of sperm retrieval as the sole endpoint, although live birth is the ultimate goal for the couples. Objectives. The main objective is to develop and evaluate the clinical benefit of a model predicting the clinical outcome of micro-TESE in heterogeneous population with NOA. The outcome of pregnancy was taken into account via assessing the association between the predicted outcome of micro-TESE and pregnancy. Materials and Methods. A development cohort of 1,292 patients with NOA and an external validation cohort of 530 patients were included. Sperm retrieval was performed using micro-TESE. Clinical outcomes, including sperm retrieval, clinical pregnancy, and live birth, were collected. We developed a model using the machine learning method random forest and provided a web-based calculator. Results. The SRR was 38.1% (492/1,292) in the development cohort and 48.5% (257/530) in the validation cohort. The final model includes etiology, AMH, sperm retrieval surgical history, testicular volume, FSH, LH, and age as predictors (ordered by variable importance). The area under the curve of our model was 0.76 (0.74–0.79) in the development cohort and 0.75 (0.71–0.79) in the external validation cohort. The decision curve analysis showed that personalized model-based surgical decision provides additional clinical benefit. The clinical pregnancy rate (CPR) and cumulative live birth rate (CLBR) were 45.3% (405/895) and 57.6% (338/587), respectively, in the overall population. For patients of different SRR, the CPR and CLBR of whom had successful sperm retrieval were similar. Discussion and Conclusion. Our model predicting the SRR of micro-TESE was generalizable and easy to use. Predicted pregnancy outcomes like CPR and CLBR could also be derived from predicted SRR. A model-based surgical decision after personalized consultation would be beneficial to patients with NOA.

Background. Fuzheng Yiliu decoction (FZYLD) was a traditional prescription with an antitumor effect. We aimed to explore the antitumor effect of FZYLD and its active ingredient, quercetin, on prostate cancer (PCa). Methods. The effective components and potential targets of FZYLD were obtained from the TCMSP, Herb, and Batman databases. The relationship between the active compounds of FZYLD and PCa’s potential targets or pathways was analyzed by Cytoscape 3.8.0 software and the String database. The compound composition of FZYLD was detected by HPLC. The effects of quercetin, with the most effective active ingredient of FZYLD, on PC-3 cell growth, metastasis, and PI3K/AKT pathway were seen by CCK-8 Kit, transwell experiment, TUNEL assay, nude mouse tumorigenesis test, and Western blot analysis. Results. Through network pharmacological analysis, we screened 195 effective active components of FZYLD, covering 290 targets, of which 198 were related to PCa. Quercetin, luteolin, kaempferol, anhydroicaritin, and 7-O-methylismucronulatol were important active compounds. MAPK1, AKT1, MAPK3, STAT3, and Jun were common targets of PCa and FZYLD. Our in vivo and in vitro experimental results confirmed that quercetin inhibited PCa’s growth, cell migration, and the PI3K/AKT pathway and promoted cell apoptosis. Conclusions. As predicted by the network pharmacological strategy and verified by the basic experimental results, FZYLD might play an antitumor role through multiple components, targets, and pathways. These results provide a new basis for developing and applying FZYLD and its compound quercetin.