Testicular Injury Research Articles

Selenium mitigates methotrexate-induced testicular injury: Insights from male NMRI mice model.

Chemotherapy, particularly with methotrexate (MTX), often elicits testicular toxicity, leading to impaired spermatogenesis and hormone imbalances. This study aimed to investigate the potential protective effects of selenium (Se) against MTX-induced testicular injury. Male mice were divided into control, MTX, Se, and MTX + Se groups. Histopathological examination involved the preparation of testicular tissue sections using the Johnsen's tubular biopsy score (JTBS) for spermatogenesis evaluation. Biochemical tests included the assessment of testosterone, malondialdehyde (MDA), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to analyze the expression of caspase 3 (casp3), tumor protein 53 (p53), B-cell lymphoma 2 (Bcl2), and Bcl2-associated X protein (Bax) genes. Statistical analysis was performed using ANOVA and Tukey's tests (p < .05). Histopathological analysis revealed significant testicular damage in the MTX group, with decreased spermatogenesis and Leydig cell count, while Se administration mitigated these effects, preserving the structural integrity of the reproductive epithelium. Biochemical analysis demonstrated that MTX led to elevated malondialdehyde (MDA) levels and reduced testosterone, LH, and FSH levels, suggesting oxidative stress and Leydig cell dysfunction. Gene expression analysis indicated that MTX upregulated proapoptotic genes (casp3, p53, and bax) while downregulating the antiapoptotic Bcl2 gene. In contrast, Se treatment reversed these trends, highlighting its potential antiapoptotic properties. Our findings underscore the potential of Se as a therapeutic agent to mitigate the reproductive toxicity associated with MTX-induced testicular injury. Se exerts protective effects by regulating oxidative stress, preserving hormone balance, and modulating apoptotic pathways. These results suggest that Se supplementation could be a promising strategy to alleviate chemotherapy-induced testicular damage and preserve male fertility.

Naringin mitigates testicular injury and associated neuronal toxicity in lead-exposed cockerel chicks.

Lead (Pb) poisoning affects multiple organs including the reproductive system. The experiment was performed to explore the protective effect of naringin on testicular apoptosis, neuronal dysfunction and markers of stress in cockerel chicks. Thirty-six cockerel chicks were used for this study, and randomly grouped into six chicks per group viz. control, Pb only (600 ppm), Pb and naringin (80 mg/kg), Pb and Naringin (160 mg/kg), naringin only (80 mg/kg) and naringin only (160 mg/kg), respectively, for eight weeks. Pb was administered via drinking water while naringin was administered via oral gavage. Oxidative stress indices in the brain and testes were assessed, and immunohistochemistry of TNF-α and caspase 3 was done in the brain and testes, respectively. Lead administration induced inflammatory and testicular apoptosis cascade accompanied with increased oxidative stress and upregulation of brain and testicular antioxidant enzymes in comparison to the control and Pb-only-treated cockerels. Immunohistochemistry showed significant immunoreactivity of testicular caspase 3 and TNF-α in the brain. Treatment of Pb-exposed chickens with naringin offered protection to Pb acetate-induced testicular oxidative stress, apoptosis, and neuroinflammation in cockerel chicks.

Phycocyanin alleviates alcohol-induced testicular injury in male Wistar rats.

Given the noteworthy implications of alcohol consumption and its association with male infertility, there has been a notable focus on investigating natural alternatives to mitigate its adverse effects. Thus, this study was conducted to assess the potential protective effect of phycocyanin extract derived from the blue algae Arthrospira (Spirulina) platensis against ethanol-induced oxidative stress, disturbances in testicular morphology, and alterations in sperm production. Male rats were divided into four groups (five rats each): the control group received a saline solution, the ethanol exposed group (EtOH) was subjected to intraperitoneal injections of 10 mL/kg of ethanol solution at a concentration of 38% (v/v), the phycocyanin alone treated group (P) received oral administration of phycocyanin at a dosage of 50 mg/kg, and the phycocyanin-cotreated group (PE) was given oral phycocyanin followed by ethanol injections. All treatments were administered over a period of 14 days. Our findings demonstrated that ethanol exposure induced reproductive toxicity, characterized by reduced sperm production and viability, alterations in testicular weight and morphology, increased lipid peroxidation levels, and elevated oxidative enzyme activity. In addition, the ethanol-intoxicated group showed perturbations in serum biochemical parameters. However, the simultaneous exposure to ethanol and phycocyanin exhibited a counteractive effect against ethanol toxicity. The results showed that supplementation of phycocyanin prevented oxidative and testicular morphological damage-induced by ethanol and maintained normal sperm production, and viability.

Silver Nanoparticles Loaded with Oleuropein Reduce Doxorubicin-Induced Testicular Damage by Regulating Endoplasmic Reticulum Stress, and Apoptosis

Doxorubicin (DOX) is the most used chemotherapeutic agent for treating solid tumors. DOX treatment may lead to testicular damage using oxidative stress, resulting in infertility. These adverse effects may be prevented by the activation of antioxidant systems.Oleuropein (OLE) is a powerful flavonoid with several ameliorative effects, including antioxidative, antiproliferative, and anti-inflammatory. It would be more efficient and applicable in treating chronic human diseases if its poor bioavailability improves with a nano-delivery system. The current study aims to assess the histopathological changes and antioxidative effects of OLE loaded with silver nanoparticles oleuropein (OLE-AgNP) on the testicular injury triggered by DOX in rats.Forty-eight male albino rats were randomly divided into six groups as follows: the control, DOX (2.5 mg/kg), OLE (50 mg/kg), AgNP (100 mg/kg), OLE + AgNP (50 mg/kg), OLE (50 mg/kg) + DOX (2.5 mg/kg), AgNP (100 mg/kg) + DOX (2.5 mg/kg), and OLE-AgNP (50 mg/kg) + DOX (2.5 mg/kg) for 11 days. Oxidative stress, inflammation, apoptosis, endoplasmic reticulum stress markers, sperm analysis, and histopathological analyses were performed on testicular tissues taken from rats decapitated after the applications and compared between the experimental groups. The tissue MDA level was lower in the OLE and OLE+AgNP-treated groups than in the DOX-treated group. In addition, SOD and GSH levels significantly increased in both the OLE and OLE+AgNP-treated groups compared to the DOX group.Both OLE and OLE+AgNP, particularly OLE+AgNP, ameliorated DOX-induced testicular tissue injury, as evidenced by reduced injury and improved seminiferous tubules and spermatocyte area. In addition, OLE and OLE+AgNP, especially OLE+AgNP, inhibited DOX-induced testicular tissue inflammation, apoptosis, and endoplasmic reticulum stress.The findings suggest that nanotechnology and the production of OLE+AgNP can ameliorate DOX-induced testicular damage.Graphical abstract

Protective Effect of Curcuminoids Consumption on Cadmium-Induced Testicular Injury in Albino Rats

This study evaluated the protective effects of curcuminoids against cadmium-induced testicular injury in Albino rats. Male albino rats were divided into nine groups, group 1 (control), groups 2-4 received 120 mg/kg, 240 mg/kg, and 360 mg/kg curcuminoids daily for 28 days without testicular injury. Group 5 received 20 mg/kg cadmium chloride (CdCl2) solution every other day for 28 days (positive control), while group 6 received 20mg/kg CdCl2 + 240 mg/kg curcuminoids every other day for 28 days. Group 7 received 20mg/kg CdCl2 every other day for 28 days, then treated with 240 mg/kg for 14 days. Group 8 received 20 mg/kg CdCl2 solution every other day for 28 days, then treated with 240 mg curcuminoids for 28 days. Group 9 received 20 mg/kg CdCl2 solution every other day for 28 days and left to recover 28 days. Serum and seminal plasma malondialdehyde, catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase were assayed using Spectrophotometry technique. Semen analysis was determined microscopically. Sperm motility and count were significantly reduced, acrosome defect and percent abnormal sperm morphology were increased among the positive control group when compared with negative control group (p&lt;0.05). Serum GPX, GSH, and SOD, semen GPx , GSH and SOD were significantly reduced (p&lt;0.001), while MDA was significantly increased (p&lt;0.001) in CdCl2 administered rats than negative control. The supplementation of Curcumins resulted in the improvement of sperm quality indices in a dose-dependent manner. Curcumin supplementation may significantly reverse the adverse effects of cadmium chloride testicular injury.

Repairing Effect of Mesenchymal Stem Cells on Lead Acetate-Induced Testicular Injury in Mice.

Lead acetate can cause testicular damage in males. In this study, we assessed the repairing effects of human umbilical cord mesenchymal stem cells (MSCs) on testicular injury caused by lead acetate in mice. MSCs were injected into mice with testicular injury by intraperitoneal injection, and the organ coefficient of reproductive organs, sperm motility, hormone level and antioxidant index of mice were tested. Compared with the normal group, the coefficient of reproductive organs and sperm motility were reduced in the model group, and histopathology showed obvious testicular injury, proving successful modeling. Compared with the model group, the reproductive organ coefficient and sperm motility were improved in the experimental group, and histopathology showed that the testicular injury could be significantly improved. Sex hormone secretion tends to be normal, and the antioxidant index increased. Sequencing results showed that there were 485 upregulated genes and 172 downregulated genes between the model group and the control group, and 210 upregulated genes and 482 downregulated genes between the experimental group and the model group. Differentially expressed genes are mainly concentrated in AMP-activated protein kinase (AMPK) signaling pathway, apoptosis signaling pathway, and arginine biosynthesis signaling pathway. Overall, MSCs can significantly improve the degree of damages to mice testis caused by lead acetate and have a certain repairing effect.

Is there any effect of lidocaine on ischemia/reperfusion injury in testicular torsion? An experimental study.

This experimental study aimed to evaluate the potential protective effects of lidocaine on ischemia-reperfusion injury resulting from testicular torsion/detorsion in rats. A total of 18 male rats were randomized into three groups. Group 1 served as the control group. Group 2 was designed to evaluate testicular ischemia-reperfusion injury using a torsion/detorsion model. In Group 3, the treatment group, a similar ischemia-reperfusion model was used as in Group 2. Additionally, lidocaine at a dose of 15 mg/kg was administered intraperitoneally five minutes before reperfusion. Blood biochemical analyses and testicular histopathological evaluations were conducted. Blood biochemical analysis showed that malondialdehyde (MDA) and protein carbonyl (PC) levels were significantly higher in Group 2 compared to the other groups (p<0.001 and p=0.008, respectively). Proinflammatory cytokine levels, including interleu-kin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha), were lower in Group 3 than in Group 2 (p<0.001, p=0.007, and p=0.026, respectively). Antioxidant enzyme activities, including glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), were higher in Group 3 compared to Group 2 (p=0.005 and p=0.025, respectively). Histopathological evaluations revealed significant improvements in all testicular damage scores, including hemorrhage, edema, vasocongestion, and inflammation in Group 3 compared to Group 2 (p=0.015, p=0.035, p=0.015, and p=0.034, respectively). Additionally, there was a notable improvement in the Johnsen score in Group 3 compared to Group 2 (p=0.034). Lidocaine, an effective local anesthetic, significantly alleviates the effects of testicular ischemia-reperfusion injury.

Umbilical Cord–Derived Mesenchymal Stem Cells Improve Ornidazole‐Induced Asthenozoospermia in Rats via Activation of the AKT/mTOR Pathway

Objective: Mesenchymal stem cells (MSCs) have been highly confirmed for their critical role in the treatment of different diseases. This study focuses on the mechanism of umbilical cord–derived MSCs (UC‐MSCs) in the treatment of ornidazole (ORN)‐induced asthenozoospermia (AS) in rats via the AKT/mTOR pathway.Methods: An animal model of AS was established in ORN‐induced rats, followed by treatment of UC‐MSCs and rapamycin (autophagy activator) or MK‐2206 (AKT inhibitor). The sperm motility, concentration, and viability of rats were measured by an automatic sperm analyzer. Hematoxylin and eosin (HE) staining was conducted to observe the pathological injury of testicular tissue in rats. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was utilized to evaluate the apoptosis rate of testicular cells. Western blot analysis was performed to determine the expression of apoptosis‐related proteins, autophagy‐related proteins, and AKT, p‐AKT, mTOR, and p‐mTOR. The rate of light chain 3 (LC3)–positive cells in testicular tissue was detected by immunohistochemistry (IHC).Results: In ORN‐induced AS rats, sperm motility, concentration, and viability as well as the number of mesenchymal cells and spermatogenic cells were significantly decreased, spermatogenic tubule space, apoptosis rate, and cleaved caspase‐3, LC3II/I, Beclin‐1, and LC3‐positive cell rates were increased, and Bcl2 was downregulated. UC‐MSCs could improve sperm quality and testicular injury in AS rats by inhibiting excessive autophagy. Besides, UC‐MSCs could activate the AKT/mTOR pathway. Moreover, inhibition of the AKT/mTOR pathway partially reversed the therapeutic effect of UC‐MSCs on ORN‐induced AS rats.Conclusion: UC‐MSCs inhibit autophagy and improve sperm quality in AS rats through the AKT/mTOR pathway, highlighting a new idea for the treatment of AS.

Flaxseed oil attenuates PFOS-induced testicular damage by regulating RNA alternative splicing.

Background: Perfluorooctane sulfonate (PFOS) is a persistent, widely present environmental pollutant, and its toxicity to male reproduction has gradually attracted attention. Flaxseed oil (FO) is a dietary oil abundant in α-linolenic acid and has been demonstrated to possess multiple health benefits. However, whether FO protects against PFOS-induced testicular injury and its mechanism remain unclear. Methods: C57/BL6 mice were gavaged with different concentrations of FO or PFOS (10 mg kg-1) for 28 days. Blood and testicular tissues were collected for histopathology, proteomics, and biochemical and molecular analyses. Results: Our results showed that FO supplementation significantly attenuated PFOS-induced testicular injury, as indicated by histopathological changes, decreased oxidative stress level, increased sperm count, decreased rate of sperm malformation, and improved functional markers of spermatogenesis. Proteomic analysis showed that differentially expressed proteins were notably enriched in spliceosome pathways. Machine learning algorithms were used to screen the hub gene, and PRPF3 and PUF60 proteins were found to be important for FO to exert protective benefits to testicular injury. Western blot results confirmed that FO supplementation could increase the protein expression of PRPF3 and decrease the protein expression of PUF60 in PFOS-exposed mice. Conclusions: This study revealed that FO can alleviate PFOS-induced testicular dysfunction by regulating RNA alternative splicing. The spliceosome-related proteins PRPF3 and PUF60 may be the potential targets for FO to alleviate PFOS-induced testicular injury. FO supplementation may be an effective dietary intervention to prevent adverse effects of PFOS on testes.

Diosmin protects the testicles from doxorubicin-induced damage by increasing steroidogenesis and suppressing oxido-inflammation and apoptotic mediators.

Cancer chemotherapy with doxorubicin (DOX) has been linked to serious testicular damage and spermatotoxicity due to the induction of oxidative stress, inflammation, and apoptosis. Thus, the current study was carried out to assess the potential ameliorative impact of diosmin, an antioxidant drug, against DOX-mediated spermatoxicity and testicular injury in rats. In the experimental protocol, rats were grouped into 4: Group 1 received vehicle and saline for 8 weeks while group 2 received diosmin and saline concomitantly for 8 weeks. Group 3 was given 3 mg/kg intraperitoneal DOX once every 7 days for 8 weeks. Group 4 was given 40 mg/kg of diosmin orally for 56 days followed by DOX diosmin administration after one hour. After 56 days of treatment, sperm quality, hormonal testing, biochemical parameters, and histological alterations in the testes were evaluated. DOX-induced reduce spermatogenic function, testicular 3- and 17β-Hydroxysteroid dehydrogenases, and serum follicle stimulating hormone, luteinizing hormone, and testosterone. It also enhanced inflammation, testicular oxidative damage, and apoptosis. The histopathologic examinations corroborated the biochemical results obtained. Significantly, diosmin treatment reduced DOX-induced injury, as evidenced by restored testicular architecture, increased steroidogenesis, preservation of spermatogenesis, suppression of oxide-inflammatory response, and apoptosis. It was found that through diosmin antioxidant, anti-apoptotic, and anti-oxido-inflammatory it presents a possible therapeutic alternative for protecting testicular tissue against DOX's harmful effects.

Alpha-pinene alleviates CCl4-induced renal and testicular injury in rats by targeting oxidative stress, inflammation, and apoptosis.

Renal and testicular disorders are primarily associated with oxidative damage and inflammation. Here, alpha-pinene (a type of monoterpene) was investigated for its effect on oxidative/nitrosative stress and the expression of inflammatory and apoptotic factors in the kidneys and testes of rats treated with CCl4. CCl4 was injected intraperitoneally (IP) at a dose of 2 ml/kg (twice a week for six weeks). Alpha-pinene (50 mg/kg/day, IP) was also treated during the same period. CCl4 increased the level of malondialdehyde (P<0.01 in the kidney and P<0.001 in the testis) and nitric oxide (P<0.001 in the kidney and P<0.01 in the testis) and decreased the levels of glutathione (P<0.05) in the kidneys and testicles of rats. CCl4 also reduced the catalase enzyme activity in the kidneys (P<0.05) but did not affect its activity in the testis. In addition, CCl4 enhanced the mRNA expression of TNF-α (P<0.01), nuclear factor-κB (P<0.05), and Bax (P<0.05 in the kidney and P<0.01 in the testis) and decreased the expression of Bcl-2 (P<0.05) in both organs. Alpha-pinene prevented all the mentioned changes, but it did not influence the expression of Bcl-2 in the kidneys of rats receiving CCl4. Alpha-pinene may have the potential to prevent renal and testicular diseases by strengthening the antioxidant system in the kidneys and testis, and inhibiting oxidative/nitrosative stress, inflammation, and apoptosis caused by CCl4.

Gallic acid attenuates torsion/detorsion-induced testicular injury in rats through suppressing of HMGB1/NF-κB axis and endoplasmic reticulum stress.

It was aimed to evaluate whether gallic acid (GA) have a beneficial effect in the testicular ischemia/reperfusion injury (IRI) model in rats for the first time. Testicular malondialdehyde, 8-hydroxy-2'-deoxyguanosine, superoxide dismutase, catalase, high mobility group box 1 protein, nuclear factor kappa B, tumor necrosis factoralpha, interleukin-6, myeloperoxidase, 78-kDa glucose-regulated protein, activating transcription factor 6, CCAAT-enhancer-binding protein homologous protein and caspase-3 levels were determined using colorimetric methods. The oxidative stress, inflammation, endoplasmic reticulum stress and apoptosis levels increased statistically significantly in the IRI group compared with the sham operated group (p < 0.05). GA application improved these damage significantly (p < 0.05). Moreover, it was found that the results of histological examinations supported the biochemical results to a statistically significant extent. Our findings suggested that GA may be evaluated as a protective agent against testicular IRI.

Shenqi Qiangjing Granules Ameliorate Asthenozoospermia in Mice by Regulating Ferroptosis through the METTL3/GPX4 Signaling Axis.

Asthenozoospermia is a leading cause of male infertility, yet current pharmacotherapies yield suboptimal outcomes, underscoring the urgent need for novel treatment modalities. Herein, we induced asthenozoospermic mouse models using busulfan and investigated the therapeutic effects of Shenqi Qiangjing Granules (SQ) on testicular pathology, serum sex hormone and steroidogenic enzyme levels, and ferroptosis. Furthermore, utilizing GC-1 spg cell lines, we elucidated the role of the METTL3-mediated m6A modification in GPX4 mRNA stability. Treatment with SQ or Fer-1 (an inhibitor of ferroptosis) significantly ameliorated testicular pathological injury, restored abnormal serum sex hormone levels, and enhanced testicular steroidogenic enzyme expression, highlighting the therapeutic potential of targeting ferroptosis in asthenozoospermia. In elucidating the molecular mechanism of METTL3 in ferroptosis, we found that METTL3 regulates GPX4 mRNA stability, subsequently impacting ferroptosis and sperm quality. Knockdown of METTL3 mimicked the effects of SQ treatment, while overexpression of METTL3 partially reversed SQ-mediated effects on ferroptosis and asthenozoospermia, underscoring the pivotal role of METTL3 in SQ therapy. In conclusion, the METTL3-GPX4-ferroptosis axis emerges as a novel regulatory pathway in the pathogenesis of asthenozoospermia. Targeting this axis, particularly through interventions such as SQ treatment, holds promise for the management of male infertility.

Assessment of Parental Awareness and Knowledge Regarding Testicular Torsion in the Aseer Region of Saudi Arabia: A Cross-sectional Study

Abstract Background: Testicular torsion (TT) is a medical emergency that requires immediate attention to prevent testicular injury. It is crucial for parents to be aware of this condition, as early recognition and timely medical attention can significantly improve the outcome for affected individuals. This study aimed to assess the level of awareness and knowledge of TT among parents in the Aseer region of Saudi Arabia using a survey-based approach. Methods: The survey included questions about the participants’ awareness of TT, its symptoms, risk factors, and recommended management. The findings of the study revealed a significant lack of parental awareness and knowledge regarding TT in the Aseer Region of Saudi Arabia. Results: The survey showed that 62.9% of parents were unsure and unable to differentiate a normal testicle. However, the majority (82.0%) believed that society needs to be more aware of TT and 75.6% expressed concern about the possibility of their child experiencing TT. Conclusion: Efforts should be made to educate parents about the condition, its symptoms, and the importance of timely intervention to prevent testicular damage. Increasing awareness can lead to early recognition and appropriate medical care, reducing the risk of complications associated with TT.

Anti-oxidant and anti-apoptotic effects of royal jelly against polystyrene microplastic-induced testicular injury in mice.

In recent years, microplastics (MPs), which are novel environmental contaminants measuring 5 mm in diameter, have garnered considerable attention. However, information regarding substances that can mitigate the dangers of MPs for animals remains extremely limited. Ninety days were devoted to the exposure of mature male mice to royal jelly (RJ) and 2 µm virgin polystyrene microplastics (PS-MPs) in this study. Pre-implantation embryo development; the structure of testis tissue; the gonadosomatic index; sperm parameters; RNA damage in germinal cells; the anti-oxidant capacity of the entire testis; and the activity of anti-oxidant enzymes in serum and testicular tissue, including TAC, SOD dismutase, CAT, GSH, and MDA, histomorphometric indices of the testis (tubular differentiation index, spermatogenesis index, and repopulation index), steroidogenic foci, and the quantity of apoptosis were assessed in the testis, respectively, through the measurement of pro-apoptosis (p53, Bax, and Caspase-3) and anti-apoptosis (Bcl-2) factors, as well as Hsp70 mediator. The results indicate that concurrent administration of RJ can confer a protective effect on mice exposed to microplastics by maintaining the structure of mitochondria and enhancement of the anti-oxidant defense system. Furthermore, RJ co-treatment decreased apoptosis and oxidant/anti-oxidant status, enhanced pre-implantation embryo development, and improved sperm characteristics and RNA damage in germ cells. The data confirm that royal jelly could protect the testis structure against polystyrene microplastic-induced testicular injury through anti-oxidant and anti-apoptotic properties.

Zeólito anula danos testiculares induzidos por cádmio em ratos: implicação da via NF-κB/ TNF-α/IL-1β

ABSTRACT Cadmium (Cd) is an environmental pollutant affecting various tissues and organs, including the testis. Many studies demonstrated that Cd toxicity causes testicular impairment through oxidative stress and inflammatory action. Therefore, this study aimed to demonstrate Cd's testicular toxicity and the protective action of zeolite against cadmium's deleterious effects. Adult male rats were given Cd at a dose of 30mg/kg/day for 28 consecutive days with or without zeolite, which was given at a dose of 100mg/kg/day for 28 days. Testis weight, sperm (count, motility, and abnormalities), serum testosterone and luteinizing hormone (LH), testicular enzymes Acid phosphatase (ACP) and Alkaline phosphatase(ALP), inflammatory cytokines Tumor Necrosis Factor Alpha (TNF-α) , interleukin-1beta (IL-1β) , and Nuclear Factor Kappa B (NF-κB) and oxidative stress were evaluated. Herein, we found that cadmium caused alterations in sperm characteristics, sex hormone disturbance, decline in testicular enzymes, elevated malondialdehyde (MDA) contents, decreased glutathione (GSH), increased Nuclear Factor Kappa B (NF-κB) and pro-inflammatory cytokines Tumor Necrosis Factor Alpha (TNF-α) and interleukin-1beta (IL-1β) levels in testis homogenate. In contrast, zeolite significantly amended these deleterious effects, and the potential mechanism involved the downregulation of Nuclear Factor Kappa B (NF-κB), Tumor Necrosis Factor Alpha (TNF-α) and interleukin-1beta (IL-1β), restoring glutathione (GSH) and reducing malondialdehyde (MDA). Also, zeolite was associated with an increased rate of pregnancy. Our data suggested that oxidative stress and inflammation are responsible for Cd-induced testicular injury and co-administration of zeolite exerts a protective effect via NF-κB /TNF-α/IL-1β pathway.

Omega-3 fatty acids abrogates oxido-inflammatory and mitochondrial dysfunction-associated apoptotic responses in testis of tamoxifen-treated rats.

Tamoxifen (TAM) is a widely used drug in patients with gynecomastia and breast cancer. TAM exerts its anticancer effects via its antiestrogenic activities. Unfortunately, TAM has been reported to exert gonadotoxic effects on male testes. Therefore, this study was designed to explore the possible associated mechanisms involved in TAM-induced testicular dysfunction and the possible ameliorative effects of omega-3 fatty acids (O3FA). Animals were randomly divided into control, O3FA, TAM, and TAM + O3FA. All treatment lasted for 28 days. TAM exposure impaired sperm qualities (count, motility, and normal morphology) and decreased testicular 3β-HSD and 17β-HSD. It was accompanied by a decline in serum testosterone and an increase in estradiol, luteinizing and follicle-stimulating hormones. These observed alterations were associated with an increase in testicular injury markers, oxido-inflammatory response, and mitochondria-mediated apoptosis. These observed alterations were ameliorated by O3FA treatments. O3FA ameliorated TAM-induced testicular dysfunction in male Wistar rats by modulating XO/UA and Nrf2/NF-kb signaling and cytochrome c-mediated apoptosis in TAM-treated rats.

Testicular Injury of Acrylamide in Rats and Potential Protection of Coenzyme Q10 and Rosuvastatin

Testicular Injury of Acrylamide in Rats and Potential Protection of Coenzyme Q10 and Rosuvastatin

Lycopene inhibits apoptosis of mouse spermatocytes in varicocele via miR-23a/b-induced downregulation of PROK2.

Context The varicocele is the leading cause of male infertility and can impair sperm quality and testicular function through various mechanisms. In our previous study, we found that lycopene could attenuate hypoxia-induced testicular injury. Aims To illustrate the detailed mechanism of lycopene on spermatocytes. Methods The effect of lycopene on GC-2 cells under hypoxia were detected by flow cytometry and western blot assay. miR-seq was used to determine miRNA expression in varicocele rat model testes. The function of miR-23a/b were determined by flow cytometry and western blot assay. Key results We demonstrate that lycopene could alleviate hypoxia-induced GC-2 cell apoptosis and could elevate miR-23a/b expression of the hypoxia model in vivo and in vitro . The miR-23a and -23b mimics could reduce the hypoxia-induced GC-2 cell apoptosis. Both miR-23a and -23b could directly bind with prokineticin 2 (PROK2) mRNA and downregulate its expression. Conclusions Lycopene could attenuate hypoxia-induced spermatocyte injury through the miR-23a/b-PROK2 pathway. Implications Lycopene may be an effective treatment for varicocele to improve testicular impairment.

Propolis attenuates diabetes-induced testicular injury by protecting against DNA damage and suppressing cellular stress.

Introduction: Propolis has a wide range of biological and pharmacological actions, including antioxidant properties-particularly its phenolic and flavonoid constituents-that could potentially protect the reproductive system from oxidative damage. Method: Four groups were allocated 40 male Wistar rats each. The vehicle was given to the first group's normal control rats negative control. The second, third, and fourth groups of diabetic rats were given vehicle (diabetic control) and propolis orally at 50 and 100mg/kg, respectively, for 8weeks. Diabetes was induced in rats via injection of nicotinamide and streptozotocin (STZ). Fasting blood glucose (FBG) and insulin levels, homeostatic model assessment for insulin resistance (HOMA-IR), and semen analysis were assessed. In addition, assessments of serum reproductive hormones, including total testosterone (TTST), estradiol (E2), follicle-stimulating hormone luteinizing hormone (LH), and prolactin (PRL), were measured at the end of the study. Tissue total testosterone, E2, and dihydrotestosterone were also evaluated. Serum and tissue oxidative enzymes, including catalase (CAT), superoxide dismutase, and glutathione peroxidase activities, were examined, and malondialdehyde content was determined. The pancreatic and testicular tissues were histopathologically examined, and proliferating cell nuclear antigen (PCNA) and B-cell lymphoma 2 (Bcl-2) in testicular tissue were immunohistochemically analyzed. Testicular tissue was examined for DNA integrity using a comet assay. Results: Compared to the STZ-control group, propolis greatly decreased FBG levels and improved the glycemic status of diabetic rats. In comparison to the STZ-DC group, propolis increased the number of sperm cells and the percent of morphologically normal and viable sperm in male rats, improving their fertility. Propolis also restored the pancreatic islets, protected the testis from oxidative stress, and increased levels of reproductive hormones in the blood, especially testosterone. Moreover, propolis at high doses demonstrated a strong positive response for Bcl-2 and a negative expression of proliferating cell nuclear antigen in spermatogenic cells. Conclusion: The data obtained strongly indicate that STZ causes severe impairments to the testis whereas propolis, acting as an antioxidant, protects against the adverse effects of STZ on the testis.