Molecular mechanism behind methamphetamine-induced damages in testicular tissue: Evidences for oxidative stress, autophagy, and apoptosis.

Methamphetamine (METH) is shown to cause massive oxidative stress and apoptosis in testicular tissue. This study attempted to investigate the possible effects of METH chronic administration on the crosstalk between oxidative DNA damage (ODD), the ODD repairing process, autophagy, and apoptosis in testicular tissue. For this purpose, 20 rats were divided into control and METH (2.5 mg/kg)-received groups (N = 10 rats/group). Following 7 days, the tubular differentiation (TDI) and spermiogenesis (SPI) indices, histomorphometric alterations, intracytoplasmic carbohydrate and lipid storage in germ and Sertoli cells along with expression levels of proliferating cell nuclear antigen (PCNA), as a key element in regulating base excision repair (BER) enzymes expression/activity were assessed. Moreover, the expression levels of uracil-DNA (UDG) and methylpurine (MPG) DNA glycosylases and microtubule-associated protein light chain 3 (LC3-I/II), and apoptotic cells distribution in testicular tissue were evaluated. Observations revealed that METH significantly suppressed spermatogenesis and spermiogenesis development, altered intracytoplasmic carbohydrate and lipid storage, increased ODD, and suppressed the PCNA expression compared to the control group (p < 0.05). Furthermore, METH-received animals exhibited a remarkable (p < 0.05) reduction in UDG and MPG, increment in LC3-I/II expressions, and apoptotic cells distribution. In conclusion, METH consumption results in a failed intracytoplasmic glucose storage (primary metabolites of Sertoli and germ cells) and oxidative stress (OS) circumstance in the testicular tissue. Further, METH can induce ODD by suppressing the expression levels of PCNA and BER enzymes, UDG and MPG. Finally, we demonstrated that METH-induced massive ODD is capable of initiating autophagy signalling that leads to progressive apoptosis in the testicular tissue.

Running exercise training-induced impact on oxidative stress and mitochondria-related apoptosis in rat's testicles.

The current study has been designed to explore the effects of running exercise training protocols (ETPs), with different intensities, on testicular redox and antioxidant capacities. Moreover, the crosstalk between oxidative stress (OS) and mitochondria-related apoptosis was analysed. To this end, 24 Wistar rats were subdivided into sedentary control, low- (LICT), moderate- (MICT), and high (HICT)-intensity continuous running ETP groups. Following 8 weeks, the Johnsen score, sperm count, testicular malondialdehyde (MDA) content, total oxidant status (TOS), and redox biomarkers, including glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) levels were evaluated. Additionally, the expression levels of Bcl-2, Bax, caspase-3, proteins involving in the mitochondria-related apoptosis, and the apoptotic index were analysed. The LICT and MICT running ETPs did not affect the spermatogenesis development, sperm count, and antioxidant and redox capacities. Accordingly, no significant changes were revealed in Bcl-2, Bax, and caspase-3 expression levels and apoptosis index compared to sedentary rats. In contrast, the HICT-induced rats showed a significant (p < 0.05) reduction in spermatogenesis development, sperm count, antioxidant and redox capacities versus control, LICT, and MICT groups. Moreover, the expression of Bcl-2 was decreased, while the Bax and caspase-3 expression levels were increased in the HICT-induced group. Finally, the apoptosis index was increased in the HICT group. In conclusion, the suppressed redox system after HICT can trigger the mitochondria-mediated ROS overload, result in OS condition in the testicular tissue, and reversely target the mitochondrial membrane permeability. All of these molecular alterations are suspected to initiate progressive mitochondria-related apoptosis after HICT.

Repro-protective role of royal jelly in phenylhydrazine-induced hemolytic anemia in male mice: Histopathological, embryological, and biochemical evidence.

To estimate the repro-protective effect of royal jelly (RJ) on phenylhydrazine (PHZ)-induced anemia's detrimental effects, 24 mature mice were divided into control group (0.10 mL normal saline; intra-peritoneally), RJ group (100 mg/kg/day; orally), experimental anemia (EA) group that received only PHZ (6 mg/100 g/48 h; intra-peritoneally), and RJ + EA (according to the previous prescription) group. After 35 days, testicular histoarchitecture, RNA damage in germinal cells, sperm characteristics, testicular total anti-oxidant capacity and malondialdehyde as well as serum testosterone levels, pre-implantation embryo development and cyclin D1 and c-myc mRNA levels at two-cell, morula and blastocyst stages were analyzed. Spermatogenesis indices were ameliorated following RJ co-administration. Moreover, RJ co-treatment reduced germinal cells RNA damage, improved sperm characteristics, boosted pre-implantation embryo development and restored androgenesis, and oxidant/anti-oxidant status. Co-administration of RJ also decreased mRNA levels of cyclin D1 and up-regulated those of c-myc in two-cell embryos, morulas and blastocysts. The findings suggest that RJ can play a repro-protective role in PHZ-induced anemia in mice through anti-oxidant defense system reinforcement and androgenesis restoration as well as cyclin D1 and c-myc expressions regulation.

Insight into the mechanism of aspartame-induced toxicity in male reproductive system following long-term consumption in mice model.

Aspartame is one of the most common consumed artificial sweeteners utilized in many food products and beverages. It has been indicated that long-term consumption of aspartame leads to reproductive toxicity but its mechanism is not well-clear. In this study we investigated mechanism of aspartame-induced reproductive toxicity in male mice. For this purpose, 36 NMRI mature male mice received three doses of 40, 80, and 160 mg/kg body weight of aspartame, respectively per day by gavage for 90 days and also a control group was considered which received 0.5 mL of normal saline as the same route. The results revealed that long-term administration of aspartame at high doses significantly (P < .05) reduced gonadosomatic index, serum concentration of pituitary-testicular axis hormones (FSH, LH, and testosterone). It also decreased sperm parameters and total antioxidant capacity, antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase), while it caused increase in nitric oxide and malondialdehyde levels in testis tissue and sperm samples. Also, it decreased attenuated testicular histomorphometric indices (tubular differentiation index, spermiogenesis index, and repopulation index), and steroidogenic foci, while increased mRNA damages and apoptosis rate, downregulated antiapoptotic (Bcl-2) and upregulated proapoptotic (P53, BAX, and caspase-3) mediators respectively in testis. These findings indicated that consumption of aspartame for a long period results in male reproductive toxicity by decrease in serum concentration of pituitary-testis axis hormones and induction of oxidative stress and apoptosis in testis.

Experimental diabetes negatively affects the spermatogonial stem cells' self-renewal by suppressing GDNF network interactions.

The present study was done to analyse the time-dependent effects of diabetes on Sertoli cells-spermatogonial stem cells' (SSCs) network interaction by focusing on glial cell line-derived neurotrophic factor (GDNF) and its special receptors, gfrα1 and c-RET as well as the Bcl-6b. In total, 40 Wistar rats were considered in; control, 20, 45 and 60 days diabetes-induced groups. An experimental diabetes was induced by STZ. The GDNF, gfrα1, c-RET and Bcl-6b expressions were evaluated. The serum level of testosterone, tubular repopulation (RI) and spermiogenesis (SPI) indices, general histological alterations, germ cells, mRNA damage, sperm count and viability were assessed. The diabetes, in a time-dependent manner, diminished mRNA and protein levels of GDNF, gfrα1, c-RET and Bcl-6b versus control group (p < .05), enhanced percentage of seminiferous tubules with negative RI, SPI, and diminished Leydig and Sertoli cells distribution, serum levels of testosterone, sperm count and viability. Finally, the number, percentage of cells and seminiferous tubules with normal mRNA content were significantly (p < .05) diminished. In conclusion, as a new data, we showed that the diabetes by inducing severe mRNA damage and suppressing GDNF, gfrα1, c-RET and Bcl-6b expressions, potentially affects the Sertoli-SSCs' network and consequently inhibits the SSCs' self-renewal process.

Berberine ameliorates experimental varicocele-induced damages at testis and sperm levels; evidences for oxidative stress and inflammation.

The present study was performed to show the ameliorative effect of berberine (BBR), as an antioxidant and anti-inflammatory agent, against experimental varicocele (VCL)-induced molecular and histological damages. For this purpose, 50 mature Wistar rats were divided into control, control-sham, VCL-sole, 50 mg/kg and 100 mg/kg BBR-treated VCL-induced groups. The tissue levels of interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), nitric oxide (NO), total antioxidant capacity (TAC), malondialdehyde (MDA), superoxide dismutase (SOD) and gluthatione peroxidase (GSH-px) as well as the mRNA levels of testicular CuZn SOD, MnSOD, EC-SOD and GSH-px were evaluated. The serum concentration of testosterone and germ cells mRNA damage were analysed. Finally, the sperm viability, motility, DNA integrity and chromatin condensation were analysed. Observations revealed that, the BBR significantly downregulated VCL-increased IL-6, TNF-α and NO levels, upregulated the CuZn SOD, MnSOD, EC-SOD and GSH-px mRNA level, decreased testicular MDA content, enhanced serum testosterone level and ameliorated testicular TAC, SOD and GSH-px levels. The animals in BBR-treated groups exhibited diminished mRNA damage versus non-treated VCL-induced group. The BBR has significantly (p < 0.05) improved sperm parameters. In conclusion, the BBR by promoting testicular antioxidant potential and by downregulating inflammatory reactions fairly promotes spermatogenesis and upregulates the sperm quality.

Zeta and hyaluronic acid assessments, novel sperm selection procedures, in animal model for male infertility.

Considering varicocele (VCL)-induced severe, progressive DNA damage, histone-protamine anomalies and low sperm production, in the current study, the experimental VCL was induced and the efficiency of hyaluronic acid (HA)-binding method (HABM) and zeta preparation procedure (ZPP) in selection of appropriate spermatozoa was compared with those spermatozoa from intact animals. Following 2 and 4 months, the histological alterations in testicular tissue, sperm count and viability were assessed to prove the VCL condition. The spermatozoa were undergone simple wash, HABM and ZPP. The chromatin condensation, active caspase-3 expression, DNA fragmentation and apoptosis index were analysed after applying selection techniques and compared with the spermatozoa from intact and VCL-induced animals, which were undergone a simple wash. Observations showed that both HABM and ZPP effectively prepared the spermatozoa with higher chromatin condensation and lower DNA damage. Meanwhile, the ZPP exerted a more preferable effect by preparing the spermatozoa with higher chromatin condensation, and lower caspase-3 expression, and DNA disintegrity versus the HABM, especially after 4 months. In conclusion, ZPP seems to exert much more reliable efficiency in selecting appropriate spermatozoa for ICSI processes, while more studies are needed to find out which one is more useful in the clinical assisted reproductive technique (ART) process.

Moderate-intensity exercise training ameliorates the diabetes-suppressed spermatogenesis and improves sperm parameters: Insole and simultaneous with insulin.

The current study was conducted to investigate the ameliorative effect of moderate-intensity exercise training insole and simultaneous with insulin on diabetes (DM)-induced pathogenesis at the testicular tissue and sperm level. For this purpose, 36 mature male Wistar rats were divided into six groups, including sedentary control (Con), exercise training (EX), sedentary experimental DM-induced (SDM), exercise training + DM-induced (DM + EX), insulin-treated sedentary DM-induced (DM + INS) and exercise training and insulin-treated DM-induced (DM + INS + EX) groups. Following DM induction, the 6-week exercise training intervention (30 min of moderate-intensity running on a treadmill, once daily [5 days/week]) was considered in EX groups. The tubular differentiation (TDI) and spermiogenesis (SPI) indices, testicular total antioxidant capacity (TAC), superoxide dismutase (SOD) and glutathione peroxidase (GPX) contents, serum testosterone and insulin levels, the apoptosis ratio and sperm parameters were assessed. The exercise in sole (EX) and simultaneous forms with INS (DM + INS + EX group) ameliorated the DM-suppressed spermatogenesis and spermiogenesis indices, up-regulated the serum testosterone and insulin levels, enhanced testicular SOD content, inhibited the apoptosis and improved almost all sperm parameters. In conclusion, exercise training, when simultaneously considered with insulin, fairly boosts the insulin-induced impacts, including the up-regulated testicular endocrine and antioxidant status, spermatogenesis and sperm quality.

Deoxynivalenol reduces quality parameters and increases DNA damage in mice spermatozoa.

This study was performed to investigate in vitro effects of deoxynivalenol (DON) on mice sperm quality parameters including viability, motility and DNA damages at various concentrations and exposure times. Mice spermatozoa were exposed to DON at 0, 2.5, 5 and 10 µM for 1, 3 and 6 hr, motility parameters were evaluated by computer-assisted analysis and viability was examined by colorimetric metabolic activity assay and HOS test. DNA damage was examined by acridine orange staining, and sperm damages via lipid peroxidation pathway were determined by malondialdehyde (MDA) content measurement. DON affected sperm parameters in a concentration- and time-dependent manner. In all test groups, the average path velocity and progressive motile spermatozoa were remarkably reduced. In comparison with the controls, after 1, 3 and 6 hr exposure to DON, viability of spermatozoa was reduced 25, 30 and 49% respectively. DON exposure at 10 µM for 6 hr resulted in 15% DNA damage and 2.5-fold more MDA generation, when compared with nonexposed spermatozoa. Our data suggest that DON causes sperm quality parameters decline in concentration- and time-dependent fashion, which attribute to the reduction in sperm metabolic activity and membrane integrity and equally to increase in lipid peroxidation rate and DNA damage.

Moderate-intensity Exercise Training in Sole and Simultaneous Forms with Insulin Ameliorates the Experimental Type 1 Diabetes-induced Intrinsic Apoptosis in Testicular Tissue.

The aim of this study was to investigate the ameliorative effect of moderate-intensity exercise training in sole and simultaneous forms with insulin on experimental type 1 diabetes (T1D)-induced apoptosis. A total of 36 mature male Wistar rats were divided into six equally sized groups, including sedentary control (Con), moderate-intensity exercise training (E-sole), sedentary T1D-induced (D-sole), moderate-exercise-trained T1D-induced (DE), insulin-treated sedentary T1D-induced (DI) and exercise-trained, and insulin-treated T1D-induced (DEI) groups. The 6-week exercise training intervention was involved 30 min of moderate-intensity running on a treadmill once daily (5 days/week). Next, tubular differentiation (TDI) and spermiogenesis (SPI) indices were assessed. The Bcl-2, Bax and caspase-3 expressions were determined using RT-PCR, immunohistochemistry and western blot techniques. Finally, the TUNEL staining was used to analyze the apoptosis ratio. The moderate-intensity exercise training in the sole and when simultaneously considered with insulin (DEI) maintained testicular cellularity, up-regulated Bcl-2 expression, reduced Bax expression and ameliorated the diabetes-induced apoptosis. We failed to show remarkable alterations in caspase-3 mRNA and protein levels in the DE group versus D-sole animals. In conclusion, the moderate-intensity exercise training is able to potentially protect testicular cells from T1D-induced intrinsic apoptosis via up-regulating Bcl-2 and downregulating Bax expressions. Moreover, it amplifies the insulin-induced anti-apoptotic impacts.

Roles of p21, p53, cyclin D1, CDK-4, estrogen receptor α in aflatoxin B1-induced cytotoxicity in testicular tissue of mice.

This study was done in order to investigate time-dependent effect of AFB1 on expression of genes involving in cell cycle check point machinery at G, S, and M phases. For this purpose, 24 mature male Swiss albino mice were randomly divided into control and test groups. The animals in test group subdivided into three groups, which received the AFB1 at a daily dose of 20 µg/kg body weight, through intraperitoneal (i.p.) route, for 7, 14, and 21 days. The p21, p53, cyclin D1, CDK4, and ERα expressions at both mRNA and protein level were analyzed by using reverse transcription PCR (RT-PCR) and immunohistochemistry, respectively. Moreover, the tubular differentiation (TDI) and spermiogenesis (SPI) indices were analyzed. Finally, the testicular DNA fragmentation was assessed by using DNA Ladder test. Observations revealed that the AFB1 remarkably (P < .05) reduced cyclin D1, Cdk4, and ERα expression at both mRNA and protein levels. Up-regulated p21 and p53 expression was revealed in AFB1-received animals, which developed time dependently. Histological examinations exhibited a significant reduction in TDI and SPI indices. Finally, the AFB1 resulted in severe DNA fragmentation. Our data showed that the AFB1 by down-regulating the cyclin D1, Cdk4, and ERα expression adversely affects cyclin D1/Cdk4 and cyclin D1/ERα interactions. Moreover, the AFB1-induced overexpression of p21 (as a kinase inhibitor), in turn results in cell cycle arrest via inhibiting the Cdk4 interaction with cyclin D1. Finally, the AFB1-induced DNA damage triggers the p53-dependent apoptosis pathway independent to p21 overexpression.

Fennel induces cytotoxic effects against testicular germ cells in mice; evidences for suppressed pre-implantation embryo development.

Foeniculum vulgare (FVE; fennel) is an aromatic plant belonging to Umbelliferae family, which is widely used in traditional societies because of its different pharmaceutical properties. To uncover the fennel-derived essential oil (FVEO)-induced effects on male reproductive potential, 24 mature male albino mice were divided into, control, 0.37, 0.75, and 1.5 mg kg-1 FVEO-received groups. Following 35 days, the animals were euthanized and the testicular tissue and sperm samples were collected. The histological alterations, tubular differentiation (TDI), spermiogenesis (SPI) indices, apoptosis ratio, and RNA damage of germinal cells were analyzed. Moreover, the sperm count, motility, viability, chromatin condensation, and DNA fragmentation were assessed. Finally, the pre-implantation embryo development including; the percentage of zygote, 2-cell embryos and blastocysts were assessed. Observations showed that the FVEO, dose dependently, increased histological damages, resulted in germ cells dissociation, depletion, nuclear shrinkage and significantly (P < .05) decreased tubular differentiation and spermiogenesis ratios. Moreover, the FVEO-received animals (more significantly in 1.5 mg kg-1 -received group) exhibited decreased sperm count, viability, and motility and represented enhanced percentage of sperms with decondensed chromatin and DNA fragmentation. Finally, the animals in FVEO-received group showed diminished zygote formation and represented decreased pre-implantation embryo development compared to control animals. In conclusion, our data showed that, FVEO albeit at higher doses, is able to adversely affect cellular DNA and RNA contents, which in turn is able to negatively affect the sperm count and morphology. All these impairments are able to negatively affect the fertilization potential as well as pre-implantation embryo development.

Nanosilver particles increase follicular atresia: Correlation with oxidative stress and aromatization.

Present study was performed in order to update the possible mechanism(s), involving in nanosilver particles (NSPs)-induced detrimental impacts in ovarian tissue. For this purpose, 24 mature female rats were divided into control and 0.5, 1, 5 mg/kg NSPs-received groups (intraperitoneally, for 35 days). Follicular growth and atresia, ovarian total antioxidant capacity (TAC), malondialdehyde (MDA), superoxide dismutase (SOD) contents, serum estrogen (E2 ) level and macrophages infiltration were investigated. Moreover, ovarian angiogenesis, cellular mRNA damage and cytochrome aromatase CYP19 expression were analyzed. The NSPs enhanced follicular atresia diminished E2, reduced TAC and SOD level, elevated MDA content and up-regulated macrophages infiltration. Cellular mRNA damage, impaired angiogenesis and diminished CYP19 expression were revealed in NSPs-received groups. Therefore NSPs by down-regulating aromatization, reduce E2 synthesis which then it leads to impaired angiogenesis. The impaired angiogenesis in turn down-regulates ovarian antioxidant status, which partially enhances follicular atresia by triggering lipid peroxidation and mRNA damage.

Simultaneous Administration of Dexamethasone and Vitamin E Reversed Experimental Varicocele-induced Impact in testicular tissue in Rats; Correlation with Hsp70-2 Chaperone Expression.

PURPOSE: This study aimed to investigate the protective effects of isolated and co-administration of vitamin E (VitE) and dexamethasone (DEX) on varicocele (VCL)-induced damages in testicular tissue. MATERIALS AND METHODS: Wistar rats were divided into five groups (n=6), including; control-sham, non-treated VCL-induced, VitE-treated VCL-induced (VitE, 150 mg/kg, orally), DEX-administrated VCL-induced (DEX, 0.125 mg/kg, i.p.), VitE+DEX-received VCL-induced animals. The antioxidant status analyses, histopathological examinations, hormonal assay and tissue levels of alkaline phosphatase (ALP) were analyzed. The germinal epithelium RNA damage and Leydig cells steroidogenesis were analyzed. Moreover, the Hsp70-2 protein expression was examined based on immunohistochemical and western blot analyses. The sperm parameters, DNA integrity and chromatin condensation were investigated. RESULTS: VitE and DEX in simultaneous form of administration significantly (P<0.05) down-regulated the tissue ALP level and attenuated the VCL-decreased GSH-px, SOD and TAC levels and remarkably (P<0.05) down-regulated the testicular malondialdehyde (MDA) and nitric oxide (NO) contents. The VCL-induced histopathological alterations significantly (P<0.05) improved in VitE and DEX-administrated animals. The VitE and DEX co-administration reduced the VCL-increased RNA damage and elevated the Leydig cells steroidogenic activity. The Hsp70-2 protein level completely (P<0.05) increased in VitE and DEX alone-and-simultaneous-administrated animals. Finally, the VitE and DEX could significantly (P<0.05) improve the VCL-decreased semen quality and improved the sperm DNA integrity and chromatin condensation. CONCLUSION: Our data suggest that Vit E by up-regulating the antioxidant status and DEX by reducing inflammation-dependent oxidative and nitrosative stresses could improve the VCL-reduced Hsp70-2 chaperone expression and ultimately protected the testicular endocrine activities and promoted the spermatogenesis process.

Evaluation of heat-shock protein A2 (HSPA2) in male rats before and after varicocele induction.

Varicocele is a major cause of infertility and may impair spermatogenesis. This study evaluated the molecular consequences of varicocele on the induction of heat-shock proteins, intracellular chaperones involved in stress responses, and of the ubiquitin-proteasome system, which is participates in the removal of defective sperm in the testis and epididymis. Wistar rats were randomly divided into three groups: surgically induced left varicocele, sham-operated, and untreated controls. Two months after surgery, we observed significantly reduced sperm parameters, DNA integrity, and protamine content in the sperm retrieved from the left epididymis compared to the right epididymis in the varicocele group, as well as compared to sperm retrieved from the left epididymis of the sham and control groups. According to Western blot analysis, we observed significantly higher HSPA2 expression in testicular tissue from the left testis compared to the right testis in the varicocele group or the left testis of the control group. Immunohistochemical analysis showed that expression of HSPA2 was higher in the round spermatid and sperm from the left varicocele compared to the control group. There was normally less HSPA2 expressed in the caput and corpus compared to the cauda of the epididymis in the control group, but this pattern was altered in the caput epididymis of the varicocele group. Levels of ubiquitination were also remarkably lower in the left testis of the varicocele group. Therefore, varicocele impacts expression of HSPA2 and ubiquitination.

Testosterone and vitamin E administration up-regulated varicocele-reduced Hsp70-2 protein expression and ameliorated biochemical alterations.

PURPOSE: This study was designed to evaluate the protective effects of vitamin E (VitE) and testosterone on varicocele (VCL)-induced damage in testis and sperm parameters and their effects on Hsp70-2 chaperone expression and on antioxidant status. METHODS: Wistar rats were divided into five groups: control-sham, VCL-induced, VitE-treated varicocelized (150 mg/kg, orally), testosterone-administrated varicocelized (400 µg/kg, intraperitoneally) and VitE + testosterone-received VCL-induced rats. The sperm count, DNA integrity, motility, viability and histone-protamine transition were evaluated after 60 days. The antioxidant status was analyzed by determining testicular malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide desmutase (SOD) and glutathione peroxidase (GSH-Px). Endocrine status of the testicular tissue was estimated by evaluating the Leydig cells steroidogenic activity using fluorescent analyses for cytoplasmic steroid foci and by determination of serum testosterone. The expression of Hsp70-2 protein was analyzed using imunohistochemical and western blot analyses. RNA damage of the germinal cells was examined with epi-fluorescent examination. RESULTS: VitE and testosterone administration ameliorated the varicocele-reduced Leydig cell and testosterone level. In addition, co-administration of these compounds recovered the VCL-induced reduction of TAC, SOD, and GSH-px and lowered significantly (P < 0.05) the VCL-elevated content of MDA. The treated animals revealed with a significant (P < 0.05) up-regulation of the VCL-reduced expression of Hsp70-2 protein. Moreover, VitE and testosterone significantly (P < 0.05) inhibited the VCL-increased RNA damage in germinal cells. CONCLUSION: Our data suggest that the protective effects of VitE and testosterone on VCL-induced derangements may depend on enhancing testicular antioxidant status and up-regulating endocrine activities, which enhanced the Hsp70-2 chaperone expression.

Vitamin E improved cypermethrin-induced damages in the ovary of rats; evidence for angiogenesis and p53 involvement.

This study aimed to investigate the protective effect of vitamin E (VitE) on cypermethrin (CPM)-induced damages in the ovary. Wistar rats were divided into seven groups (n=6) including; control-sham (c), CPM-received (CPM, 75 mg/kg, i.p.), and CPM and VitE-treated (VitE, 150 mg/kg, orally) for 7, 14 and 24 days. The antioxidant status determination and hormonal assays along with histological and immunofluorescent assessments were performed. The expression of p53 at mRNA level was also examined. The CPM administration affected the ovarian structure and functions as it elevated the follicular atresia and significantly (P<0.05) lowered the estradiol level, time dependently. VitE administration enhanced the CPM-reduced antioxidant capacity, gonadotropins and estradiol levels. Co-administration of VitE and CPM remarkably attenuated the CPM-induced RNA damage in granulosa and theca cells and elevated the deranged angiogenesis. The CPM-reduced micro and macro vessels distribution was significantly (P<0.05) elevated in the VitE-received animals. Expression of p53 at mRNA level was down regulated in the VitE-treated groups completely and relatively following 7 and 14 days, respectively. Our data showed that the CPM-induced biochemical and histological damages could be prevented by VitE. Moreover, protective effects of VitE attribute to its potency in enhancing the antioxidant capacity and promoting the gonadotropins secretion, which resulted in down regulation of p53 overexpression and RNA damage in follicular cells accomplished with improved angiogenesis.

Effect of running exercise training on inflammatory mediators and cytokines expression in testicular tissue; effect of exercise intensity.

The aim of this study is to investigate the impact of running exercise training protocols (ETPs) with varying intensities on inflammatory responses, with a specific focus on the interactions between inflammatory mediators, cytokines, and Leydig cell steroidogenic activity, as well as testosterone secretion. To this end, 24 Wistar rats were subdivided into sedentary control, low (LICT), moderate (MICT), and high (HICT) intensity continuous running ETP groups. After 8 weeks, the expression levels of Toll-like receptor-4 (TLR-4), nuclear factor-kappa-B (NF-KB), interleukin-6 (IL-6), interleukin-10 (IL-10), Tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and the testicular nitric oxide (NO) content were assessed and compared between groups. Moreover, the mean distributions of Leydig cells/mm2 of interstitial connective tissue, their steroidogenic activity, and serum level of testosterone were assessed. The LICT did not show any significant (p > 0.05) change in the expression levels of all aforementioned biomarkers. In contrast, both the MICT and HICT groups demonstrated a significant (p < 0.05) increase in the expression levels of TLR-4, NFK-B, IL-6, TNF-α, iNOS, and COX-2 at both the mRNA and protein levels. The testicular NO has increased in HICT and MICT groups. Despite a decrease in the distribution of Leydig cells in both the MICT and HICT groups, the HICT group exhibited a significant (p < 0.05) reduction in Leydig cell steroidogenic activity and serum testosterone levels. In conclusion, our findings revealed that ETPs can influence Leydig cell steroidogenic activity and testosterone secretion, contingent on their intensity. These effects are attributed to alterations in the expression levels of pro-inflammatory mediators and cytokines.

The Effect of Different Exercise Modalities on Sertoli-germ Cells Metabolic Interactions in High-fat Diet-induced Obesity Rat Models: Implication on Glucose and Lactate Transport, Igf1, and Igf1R-dependent Pathways.

The study aimed to uncover a unique aspect of obesity-related metabolic disorders in the testicles induced by a high-fat diet (HFD) and explored the potential mitigating effects of exercise modalities on male fertility. Thirty mature male Wistar rats were randomly assigned to control, HFD-sole, moderate-intensity exercise with HFD (HFD+MICT), high-intensity continuous exercise with HFD (HFD+HICT), and high-intensity interval exercise with HFD (HFD+HIIT) groups (n=6/group). Intracytoplasmic carbohydrate (ICC) storage, expression levels of GLUT-1, GLUT-3, MCT-4, Igf1, and Igf1R, and testicular lactate and lactate dehydrogenase (LDH) levels were assessed. ICC storage significantly decreased in HFD-sole rats, along with decreased mRNA and protein levels of GLUT-1, GLUT-3, MCT-4, Igf1, and Igf1R. The HFD-sole group exhibited a notable reduction in testicular lactate and LDH levels (p<0.05). Conversely, exercise, particularly HIIT, upregulated ICC storage, expression levels of GLUT-1, GLUT-3, MCT-4, Igf1, and Igf1R, and enhanced testicular lactate and LDH levels. These results confirm that exercise, especially HIIT, has the potential to mitigate the adverse effects of HFD-induced obesity on testicular metabolism and male fertility. The upregulation of metabolite transporters, LDH, lactate levels, Igf1, and Igf1R expression may contribute to maintaining metabolic interactions and improving the glucose/lactate conversion process. These findings underscore the potential benefits of exercise in preventing and managing obesity-related male fertility issues.

Oxidative Stress and Cell Cycle Arrest in Seminiferous Tubules Nearby Varicose Vessels: New Perspectives from Experimental Varicocele.

Varicocele (VCL) has been shown to induce severe oxidative stress in the testicular tissue resulting in 35% of males with primary infertility. To compare the exacerbating impacts of varicose on oxidative DNA damage and homeostatic antioxidant reactions in the seminiferous tubules (ST), enclosed and far from varicose vessels. Thirty mature Wistar rats were divided into control and VCL-induced groups. To approve VCL, the testicular diameters, volume, and blood circulation were measured using B-mode and Doppler ultrasonography. Next, to confirm oxidative stress (OS), the global homeostatic antioxidant biomarkers were evaluated. Moreover, the OS-induced oxidative DNA damage and homeostatic antioxidant reactions were compared between STs nearby and far from varicose vessels. Finally, to clarify the DNA damage-induced impact on the cell cycle progression, the global and local expressions of Cyclin D1, Cdk4, and p21 were examined. The VCL-induced group exhibited diminished global antioxidant status (marked with TAC, GPX, SOD, and CAT) and UNG and MPG expression levels. Moreover, the cross-sections of the VCL group represented a prominent reduction in the UNG, MPG, Cyclin D1, and cdk4, and upregulation in the p21 expression levels, more prominently in the STs nearby varicose vessels. Concerning severe oxidative DNA damage and intensive molecular changes in the STs nearby the varicose vessels, they can be considered the main cause of oxidative DNA damage in enclosed tubules. Thus, the varicose-mediated oxidative DNA damage negatively impacts the cell cycle progression in the tubules more intensively in the subcapsular area.