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.

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 role of the transsulfuration pathway in spermatogenesis of vitamin D deficient mice.

Vitamin D deficiency is a global health problem and has been linked to defective spermatogenesis and male infertility. In this study, we aimed to investigate the main enzymes involved in the transsulfuration pathway of 1-carbon metabolism, and spermatogenesis function. Therefore, sixteen male C57 mice were addressed to a control (standard diet) or vitamin D deficient (VDD) diet for 14 weeks. The results show that compared to the standard diet, VDD increased final body weight and reduced sperm quality, caused damage to the testicular structure, and decreased the serum levels of testosterone. In addition, serum concentrations of homocysteine, vitamin B12, and sperm oxidative stress markers increased. In testicular tissues, the CBS and CSE protein levels were down-regulated whereas HO-1 was up-regulated at both mRNA and protein expression levels. Within a mice deprivation model, VDD deeply suppressed testosterone and impaired spermatogenesis with oxidative stress-mediated mechanisms. The effects of the deprivation appeared to be at least in part independent of genomic and receptor-mediated vitamin D actions and suggest a specific impairment of the alternative transsulfuration pathway.

A caffeine pre-treatment and sole effect of bone-marrow mesenchymal stem cells-derived conditioned media on hyperglycemia-suppressed fertilization.

As a common metabolic disorder, hyperglycemia (HG) affects and disrupts the physiology of various systems in the body. Transplantation of mesenchymal stem cells (MSCs) has been used to control the complications of disease. Most of the therapeutic properties of MSCs are attributed to their secretome. This study aimed to investigate the effects of conditioned media extracted from sole or caffeine pre-treated bone-marrow-derived MSCs on hyperglycemia-induced detrimental impact on some aspects of reproduction. The HG was induced by intraperitoneally injection of streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg). Twenty-four male Wistar rats (190 ± 20 g) were divided into control, HG, and the hyperglycemic groups receiving conditioned media of proliferated MSCs solely (CM) or MSCs pre-treated with caffeine (CCM). During the 49-day treatment, body weight and blood glucose were measured weekly. Finally, HbA1c, spermatogenesis development, sperm count, morphology, viability, motility, chromatin condensation, and DNA integrity were examined. Also, testicular total antioxidant capacity (TAC), malondialdehyde, sperm fertilization potential, and pre-implantation embryo development were evaluated. A one-way ANOVA and Tukey's post-hoc tests were used to analyze the quantitative data. The p < 0.05 was considered statistically significant. The CM and with a higher efficiency, the CCM remarkably (p < 0.05) improved body weight and HG-suppressed spermatogenesis, enhanced sperm parameters, chromatin condensation, DNA integrity, and TAC, reduced HbA1c, sperm abnormalities, and malondialdehyde, and significantly improved pre-implantation embryo development versus HG group. The conditioned media of MSCs solely (CM) and more effectively after pre-treatment of MSCs with caffeine (CCM) could improve spermatogenesis development, sperm quality, pre-implantation embryo development, and testicular global antioxidant potential during hyperglycemia.

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.

Paroxetine treatment in an animal model of depression improves sperm quality.

Depression in mammals is known to be associated with poor reproductive capacity. In males, it has been associated with decreased efficiency of spermatogenesis as well as the production of spermatozoa of reduced structural and functional integrity. Although antidepressants are effective in correcting depressive states, there is controversy regarding their effectiveness in restoring male reproductive function. Here, using an animal model of depression induced by a forced swim test, we confirmed that depression is accompanied by impaired male reproductive function. We further show that administration of a conventional antidepressant of the serotonin reuptake inhibitor class (paroxetine) impairs male reproductive performance in terms of sperm production and quality when administered to healthy animals. Intriguingly, when paroxetine is administered to "depressed" animals, it resulted in a complete restoration of the animal's ability to produce sperm that appears to be as capable of meeting the parameters evaluated here as those of control animals. The one-carbon cycle (1CC) is one of the most important metabolic cycles that include the methionine and folate cycles and plays a major role in DNA synthesis, amino acids, and also the production of antioxidants. Our results show that depression affects the main components of this cycle and paroxetine on healthy mice increases homocysteine levels, decreases glycine and vitamin B12, while in depressed mice, it increases folate levels and decreases vitamin B12. Thus, paroxetine exerts negative impacts on male reproductive function when administered to healthy animals and it well correlate with the altered sperm parameters and functions of depressed animals, and its mechanism remains to be explored.

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.

Boosting effect of testosterone on GDNF expression in Sertoli cell line (TM4); comparison between TM3 cells-produced and exogenous testosterone.

The Glial cell-derived neurotrophic factor (Gdnf) and testosterone induce the spermatogonial stem cells (SSCs) self-renewal and spermatogenesis, respectively. In present study the stimulating role of testosterone on Sertoli cells to produce Gdnf, and the possible effect of Gdnf on Gfrα1 and c-RET expressions were investigated. The TM4 cells (line Sertoli cells) were co-cultured with [0.1, 0.2 and 0.4 (ng/ml)] of exogenous and TM3 (line Leydig cells)-produced testosterones, and consequently the TM4-produced Gdnf concentration was evaluated. Next, the SSCs were co-cultured with the TM-4 derived media (endogenous Gdnf) and exogenous Gdnf [0.1, 0.2, and 0.4 ng/ml)]. The 0.1 and 0.2 ng/ml endogenous and 3 concentrations of exogenous testosterone up-regulated the Gdnf expression versus non-treated Sertoli cells. The TM4-produced and exogenous Gdnfs, in all concentrations, up-regulated the receptors expression. In conclusion, the testosterone, solely, stimulates the Gdnf synthesis and the Gdnf, individually, amplifies its receptor's expression at mRNA and protein levels.

Moderate-Intensity Exercise Training in Association with Insulin Promotes Heat Shock Proteins 70 and 90 Expressions in Testicular Tissue of Experimental Type 1 Diabetes.

OBJECTIVE: The current research was designed to analyze the effect of moderate-intensity exercise training (MEXT), solely and simultaneous with insulin, on the network between oxidative stress and Hsp70 and Hsp90 chaperones after experimental type I diabetes (DM) induction in rats. MATERIALS AND METHODS: In the experimental study, 36 mature Wistar rats were assigned into control and experimental type I DM-induced groups, and then the diabetic animals were categorized to sedentary type I DM-induced (SDM), exercise training-sole without DM (E), exercise training DM-induced (EDM), insulin-treated sedentary DM-induced (ISDM), and exercise training insulin-treated DM-induced (EIDM) groups. After 6 weeks, Johnson's score was evaluated to analyze the spermatogenesis ratio. RESULTS: The Hsp70 and Hsp90 expression levels, testicular total antioxidant capacity (TAC), protein peroxidation ratio, testicular DNA fragmentation ratio, and mRNA damage were investigated. The animals in EDM and EIDM groups (solely and simultaneously) represented a significant (P<0.05) improvement in Johnson's score, spermatogenesis, and TAC ratios versus SDM animals. Moreover, the DM-induced DNA and mRNA damage and protein peroxidation ratio were significantly (P<0.05) recovered in EDM and ISDM groups, which was more remarkable in the EIDM group. The EDM and EIDM groups exhibited significant (P<0.05) increment in Hsp70 and Hsp90 expression levels versus the control and SEDT1 animals. However, the EIDM group exhibited no significant changes compared to the control animals. CONCLUSION: The EX could ameliorate the EDT1-induced detrimental impact by up-regulating Hsp70 and Hsp90 expressions. Meanwhile, it exerts potentially more effective impact, when it is considered simultaneously with insulin therapy.

Possible protective effects of crocin on destructive side effects of cyclo-phosphamide in mice ovarian tissue: Evaluation of histomorphometrical and biochemical changes.

One of the side effects of cyclophosphamide (CP) is low fertility. In this study, we investigated the protective role of crocin (Cr) against CP chemotherapy-induced changes in ovarian tissue. In the current study, we treated 15 female mice aged 6-8 weeks old for 21 days. The mice were distributed into three groups including control received normal saline (0.10 mL; IP), CP or sham-control group (CP once a week, 15.00 mg kg-1; IP) and experimental (CP + Cr) group received CP along with Cr (200 mg kg-1 daily; IP). After completing the procedure, levels of total anti-oxidant capacity (TAC), superoxide dismutase (SOD) and sex hormones in serum as well as malondialdehyde (MDA) in the left ovarian tissue were measured. The right ovaries were used for histological and morphological tests. The obtained data were statistically analyzed by SPSS software using ANOVA and Tukey follow-up studies. Results showed that in the CP group a significant decrease was observed in ovarian follicles, the number of corpus luteum, levels of TAC, SOD and sex hormones; while, there was a significant increase in the number of atretic follicles and mast cells and level of MDA compared to control group. Administration of Cr along with CP caused a significant ameliorative effect on the studied parameters. In conclusion, the Cr could significantly decrease the side effects caused by CP chemotherapy in mice ovarian tissue.

Insulin treatment to type 1 male diabetic rats protects fertility by avoiding testicular apoptosis and cell cycle arrest.

BACKGROUND: Uncontrolled type 1 diabetes mellitus (T1D) impairs reproductive potential of males. Insulin treatment restores metabolic parameters but it is unclear how it protects male reproductive health. Herein, we hypothesized that insulin treatment to T1D rats protects testicular physiology by mediating mechanisms associated with apoptosis and cell cycle. METHODS: Mature male Wistar rats (n = 24) were divided into 3 groups: control, T1D-induced (received 40 mg kg-1 streptozotocin) and insulin-treated T1D (Ins T1D; received 40 mg kg-1 streptozotocin and then treated 0.9 IU/100 gr of insulin for 56 days) (N = 8/group). Expression levels of intrinsic apoptosis pathways regulators (Bcl-2, Bax, Caspase-3 and p53) and core regulators of cell cycle machinery (Cyclin D1, Cdk-4 and p21) were determined in testicular tissue by immunohistochemistry (IHC) and RT-PCR techniques. The percentage of testicular apoptotic cells was evaluated by TUNEL staining. RESULTS: Our data shows that insulin treatment to T1D rats restored (P < 0.05) T1D-induced increased of caspase-3 and p53 expression in testis. Moreover, the testis of T1D rats treated with insulin exhibited increased expression of Cyclin D1 and cdk-4, and a reduced expression of p21 when compared with the expression in testis of T1D rats. Finally, insulin treatment could fairly control T1D-induced apoptosis. Accordingly, treatment of T1D rats with insulin led to a remarkable reduction (p < 0.05) in the percentage of apoptotic cells in the testis. CONCLUSIONS: Insulin treatment is able to restore the network expression of apoptosis and proliferation-related genes caused by T1D in the testis and via this mechanism, preserve the fertility of males.

Curcumin nano-micelle induced testicular toxicity in healthy rats; evidence for oxidative stress and failed homeostatic response by heat shock proteins 70-2a and 90.

This study explores the effect of curcumin nano-micelle (NCMN) on the testicular anti-oxidant status and heat shock proteins (Hsp) 70-2a and Hsp 90 expression. Therefore, 24 male Wistar rats were divided into control, 7.50 mg/kg, 15 mg/kg, and 30 mg/kg of NCMN-received groups. Following 48 days, the testicular total anti-oxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA) and glutathione (GSH), catalase (CAT) and glutathione peroxidase (GPX) activities, immunoreactivity of 8-oxodG, Hsp70-2a and Hsp90 expressions, germ cell's DNA and mRNA damages, the spermatozoa count, motility and DNA integrity were assessed. With no change in the testicular TAC level, the TOS, MDA and GSH contents were increased in the NMC-received groups. However, CAT and GPX activities were decreased. The NCMN suppressed spermatogenesis, increased immunoreactivity of 8-oxodG, stimulated the Hsp70-2a and Hsp90 expressions, and resulted in severe DNA and mRNA damages. Moreover, the NCMN-received animals exhibited remarkable reductions in the spermatozoa count, motility and DNA integrity. In conclusion, chronic and high dose consumption of NCMN initiates OS, and in response to OS, the Hsp70-2a and Hsp90 expression increases. However, considering enhanced DNA and mRNA damages and suppressed spermatogenesis, HSPs over-expression can neither boost the anti-oxidant system nor overcome the NCMN-induced OS-related damages.

Cross-link between mitochondrial-dependent apoptosis and cell cycle checkpoint proteins after experimental torsion and detorsion in rats.

The current study assessed the cross-link between mitochondria-related apoptosis and cell cycle machinery systems during ischemia and reperfusion in a rat model of testicular torsion and detorsion. The Wistar male rats were divided into control, 1 h, 2 h, 4 h and 8 h testicular torsion-induced, and 1 h, 2 h, 4 h and 8 h testicular detorsion-induced groups. The Johnson's score was analyzed. The mRNA and protein contents of Bcl-2, Bax, Caspase-3, Cyclin D1, Cdk4, P21 and P53 were investigated by sqRT-PCR and immunohistochemical staining, respectively. The apoptosis index was analyzed by TUNEL staining. The mRNA levels of bax, p53, p21 and cyclin D1 were increased, and the mRNA levels of bcl-2 and cdk4 were decreased in torsion and reperfusion-induced groups, time-dependently. The caspase-3 mRNA was increased in torsion-induced and diminished in detorsion-induced groups. A time-dependent reduction in Bcl-2+, Caspase-3+, Cyclin D1+, Cdk4+ and P53+ and increment in P21+ cells distribution per mm2 of tissue were revealed after torsion and detorsion. The apoptosis index was increased after torsion and decreased after detorsion. In conclusion, torsion-induced severe DNA damage stimulates the cyclin D1, p53 and p21 mRNA expression while more than 8 h is needed to reveal them as protein content in testicular tissue. About detorsion, decreased Cyclin D1 and Cdk4 proteins and the P53-induced transcriptional effect on p21 expression, stimulates the p21 bind to cdk4 and consequent failure in Cyclin D1/Cdk4 complex formation. This situation in association with apoptotic genes results in spermatogenesis failure.

Fabrication of chitosan-based electrospun nanofiber scaffold: Amplification of biomechanical properties, structural stability, and seeded cell viability.

The cell scaffolds should structurally be manufactured similar to the target tissue's extracellular matrix. This property should be maintained until cell differentiation. For this purpose, in the current study, electrospun nanofiber (EN) of chitosan (Ch)/polyvinyl alcohol (PVA), as a tissue-friend scaffold, was fabricated by electrospinning in different formulations and borax was utilized as an innovative cross-linking agent to up-regulate the structural and biomechanical properties. The weight loss, water absorbability, structural stability, tensile strength and biocompatibility of borax-included and non-included ENs were compared. The finest morphology, weight loss, water absorbability, structural stability in an aqueous environment, tensile strength and cell viability were found in the borax-included EN containing Ch50.00%v/PVA50.00%v. Moreover, The ENs exhibited appropriate antibacterial properties against Gram-positive and Gram-negative bacteria. In conclusion, borax can be used to improve the mechanical and biocompatibility features of the Ch/PVA-based ENs. Furthermore, it could be suggested that borax-included Ch/PVA ENs can exhibit high appropriate biological properties, candidate them as an appropriate scaffold in the field of tissue engineering. However, in vivo trials are needed to clearly their side effects and advantages.

Effects of liraglutide on sperm characteristics and fertilization potential following experimentally induced diabetes in mice.

The current study was conducted to analyze the dose-dependent effects of liraglutide against the diabetes-induced detrimental impact on sperm parameters and fertilization potential. For this purpose, 42 adult male mice were randomly divided into control (with no intervention) and experimental groups. Next, the experimental group was subdivided into diabetic, 1.20 mg kg-1 liraglutide-received diabetic, 1.80 mg kg-1 liraglutide-received diabetic, 1.20 mg kg-1 liraglutide-received non-diabetic and 1.80 mg kg-1 liraglutide-received non-diabetic groups. All chemicals were administrated subcutaneously. Following 42 days, the animals were euthanized, and sperm samples were collected. The sperm count, motility, viability, DNA integrity, and maturity were analyzed and compared between groups. Moreover, the sperm fertilization potential was investigated by in vitro fertilization (IVF). For this purpose, the preimplantation embryo development at 2-cell, 4-cell, morula, and blastocyst stages was investigated and compared. Observations revealed that diabetes significantly diminished sperm count, motility, viability, chromatin condensation, and DNA integrity percentages versus a control group. On the other hand, 1.20 mg kg-1 and 1.80 mg kg-1 of liraglutide did not improve sperm motility and viability, while ameliorated sperm count and chromatin condensation and DNA integrity in diabetic animals. The diabetic animals represented diminished preimplantation embryo development, which was not altered in liraglutide-received groups. In conclusion, at least in administrated doses, liraglutide could not improve the sperm viability and motility and, via this mechanism, could not induce an appropriate/beneficial effect on IVF outcome.

ROS and metabolomics-mediated autophagy in rat's testicular tissue alter after exercise training; Evidence for exercise intensity and outcomes.

AIMS: Oxidative damage and altered metabolic reactions are suspected to initiate the autophagy. The exercise training significantly impacts testicular antioxidant and metabolic potentials. However, the underlying mechanism(s) that the exercise-induced alterations can affect the autophagy markers remained unknown. This study explored the effect of exercise training on antioxidant and metabolic statuses of testicular tissue and uncovered the possible cross-link between these statuses and autophagy-inducers expression. MAIN METHODS: Wistar rats were divided into sedentary control, low (LICT), moderate (MICT), and high (HICT) intensity continuous training groups. Following 8 weeks of training, the testicular total antioxidant capacity (TAC), total oxidant status (TOS), glutathione (GSH), and NADP+/NADPH as oxidative biomarkers along with intracytoplasmic carbohydrate and lipid droplet patterns, lactate dehydrogenase (LDH) activity, and lactate as metabolic elements were assessed. Finally, the autophagy-inducers expression and sperm count were examined. KEY FINDINGS: With no significant impact on the oxidative biomarkers and metabolic elements, the LICT and MICT groups exhibited statistically unremarkable (p < 0.05) impacts on spermatogenesis differentiation, spermiogenesis ratio, and sperm count while increased the autophagy-inducers expression. Reversely, the HICT group, simultaneous with suppressing the antioxidant biomarkers (TAC↓, GSH↓, TOS↑, NADP+/NADPH↑), significantly (p < 0.05) reduced the testicular LDH activity and lactate level, changed the intracytoplasmic carbohydrate and lipid droplet's pattern, and amplified the classical autophagy-inducers p62, Beclin-1, autophagy-related gene (ATG)-7, and light chain 3 (LC3)-II/I expression. SIGNIFICANCE: The autophagy-inducers overexpression has occurred after HICT induction, most probably to eliminate the oxidative damage cargoes, while increased to maintain the metabolic homeostasis in the LICT and MICT groups.

High-fat diet-induced obesity amplifies HSP70-2a and HSP90 expression in testicular tissue; correlation with proliferating cell nuclear antigen (PCNA).

AIMS: Current study was conducted to uncover the effect of high-fat diet (HFD)-induced obesity on heat shock proteins 70-2a and 90 expression levels and to investigate the network between these proteins with PCNA expression, endocrine status of testicular tissue and nucleotide backbone damages. MAIN METHODS: For this purpose, 20 mature male Wistar rats were divided into two groups of control and HFD-received obese animals (n = 10/group). After 8 weeks from obesity approval, the animals were euthanized. The expression levels of Hsp70-2a, Hsp90 and PCNA were analyzed by qRT-PCR and immunohistochemical staining techniques. The Leydig cell distribution/mm2 of interstitial tissue, serum level of testosterone, testicular total antioxidant capacity (TAC), and mRNA and DNA damage were investigated. KEY FINDINGS: The obese (HFD-received) animals represented a remarkable (p < 0.05) increment in the mRNA levels of hsp70-2a and Hsp90, and the percentages of Hsp70-2a+ and Hsp90+ cells/seminiferous tubules with the same criteria. The PCNA mRNA level and the percentage of PCNA+ cells were decreased in the obese (HFD-received) group. The obesity, significantly decreased testicular TAC and with no effect on the Leydig cell distribution, but by reducing their steroidogenic activity resulted in a remarkable (p < 0.05) reduction in serum testosterone level. Finally, severe mRNA and DNA damage were revealed in the obese (HFD-received) group. SIGNIFICANCE: Therefore, considering massive testicular DNA damage in the obese (HFD-received) animals, we can conclude that an increased expression of Hsp70-2a and Hsp90 with no harmony with PCNA could not properly maintain the cellular DNA integrity and/or appropriately finalize the DNA repair process.

Different continuous exercise training intensities induced effect on sertoli-germ cells metabolic interaction; implication on GLUT-1, GLUT-3 and MCT-4 transporting proteins expression level.

Despite other tissues, the effect of different exercise training protocols (ETPs) on the expression levels of metabolic substrates transmembrane transporters in the testicular tissue, remains completely unexplored. Thus, the effects of low, moderate and high-intensity ETPs on the SCs and germ cells potentials in GLUT-1, GLUT-3 and MCT-4 expression levels was investigated in this study. The animals were assigned into 4 groups, including sedentary control, low-intensity continuous (LICT), moderate-intensity (MICT) and high-intensity (HICT) ETPs-induced groups (n = 6/group). The GLUT-1, GLUT-3 and MCT-4 expressions, cytoplasmic carbohydrate storages of SCs and germ cells, the SCs survival and the spermatogenesis and spermiogenesis rates were assessed. The LICT and MICT did not significantly alter the protein expression levels of GLUT-3 and MCT-4 in the SCs and germ cells, while decreased the GLUT-1 protein content versus the sedentary control animals. In contrast, the HICT remarkably suppressed the GLUT-1 and MCT-4 in both SCs, and germ cells and diminished GLUT-3 in SCs and increased in the germ cells. No significant changes were revealed in the cytoplasmic carbohydrate storage in the LICT and MICT groups, while significantly diminished in the HICT group. The HICT group showed a failed spermatogenesis and spermiogenesis, which were not demonstrated in the sedentary control, LICT and MICT groups. In conclusion, the HICT, by reducing the GLUT-1, GLUT-3 and MCT-4 protein contents in the SCs and reducing the SCs survival, can suppress the glucose transmembrane transport and inhibit the lactate export from SCs, which in turn, ends with failed spermatogenesis and spermiogenesis.