Testis Injury Research Articles

The protective effects of curcumin against cigarette smoke-induced toxicity: A comprehensive review.

Cigarette smoking (CS) is a crucial modifiable risk of developing several human diseases and cancers. It causes lung, bladder, breast, and esophageal cancers, respiratory disorders, as well as cardiovascular and metabolic diseases. Because of these adverse health effects, continual efforts to decrease the prevalence and toxicity of CS are imperative. Until the past decades, the impacts of natural compounds have been under investigation on the harmful effects of CS. Turmeric (Curcuma longa), a rhizomatous herbaceous perennial plant that belongs to the Zingiberaceae family, is the main source of curcumin. This review is an attempt to find out the current knowledge on CS's harmful effects and protective potential of curcumin in the pulmonary, liver, brain, gastrointestinal, and testis organs. According to the present review, simultaneous consumption of curcumin and CS can attenuate CS toxicities including chronic obstructive pulmonary disease, gastrointestinal toxicity, metabolic diseases, testis injury, and neurotoxicity. Moreover, curcumin suppresses carcinogenesis in the skin, liver, lungs, breast, colon, and stomach. Curcumin mediates these protective effects through antioxidant, anti-inflammatory, anti-apoptotic, and anti-carcinogenicity properties.

Decreased Klotho Expression Causes Accelerated Decline of Male Fecundity through Oxidative Injury in Murine Testis.

Oxidative stress is the etiology for 30-80% of male patients affected by infertility, which is a major health problem worldwide. Klotho protein is an aging suppressor that functions as a humoral factor modulating various cellular processes including antioxidation and anti-inflammation, and its dysregulation leads to human pathologies. Male mice lacking Klotho are sterile, and decreased Klotho levels in the serum are observed in men suffering from infertility with lower sperm counts. However, the mechanism by which Klotho maintains healthy male fertility remains unclear. Klotho haplodeficiency (Kl+/-) accelerates fertility reduction by impairing sperm quality and spermatogenesis in Kl+/- mice. Testicular proteomic analysis revealed that loss of Klotho predominantly disturbed oxidation and the glutathione-related pathway. We further focused on the glutathione-S-transferase (GST) family which counteracts oxidative stress in most cell types and closely relates with fertility. Several GST proteins, including GSTP1, GSTO2, and GSTK1, were significantly downregulated, which subsequently resulted in increased levels of the lipid peroxidation product 4-hydroxynonenal and apoptosis in murine testis with low or no expression of Klotho. Taken together, the loss of one Kl allele accelerates male fecundity loss because diminished antioxidant capability induces oxidative injury in mice. This is the first study that highlights a connection between Klotho and GST proteins.

Efficacy of Saudi propolis and bee pollen in the reduction of oxidative stress induced with CCl4 in a testis mice model

Low testosterone levels are caused by alcoholism, cigarette smoking, and exposure to toxic chemicals. This work focused on investigating the activities of propolis (PE) and bee pollen (BPE) extracts in reducing the oxidative stress of carbon tetrachloride (CCl4) in male mice models. The 48 male Swiss Albino mice weighed 27.5 ± 2.5 g and were divided into: Group1: Control (-) received distilled water only through oral intubation; Group 2: Control (- -) received corn oil by intraperitoneal (i.p.) injection once a day; Group 3: Control (+) received a sublethal dose of CCL4 intraperitoneally the end of the experiment. Group 4: Stander treated with silymarin at a daily dose of 200 mg/kg orally. Group 5: The mice were given 8.4 mg/ kg bw of (PE) orally. Group 6: The mice were given (BPE) extract (140 mg/kg bw) orally. After five consecutive days of treatment, all mice had testis injury in all groups except G1& G2, by a single i.p injection of CCL4 at a dose of 0.5 mL/kg (bw; 20% v/v in corn oil). The result showed a significant increase in luteinizing, follicle-stimulating, and testosterone hormone levels in the serum and semen parameters in the groups treated with PE and BPE. The histological results showed the greatest improvements in testis structures in the BPE group, which was confirmed using (Bcl-2; immunohistochemistry). These results suggest an important role of the antioxidative effects of PE and BPE in the attenuation of CCl4 oxidative stress.

Effect of Salvia miltiorrhiza Bunge extracts on improving the efficacy and reducing the toxicity of Tripterygium wilfordii polyglycosides in the treatment of rheumatoid arthritis

Ethnopharmacological relevanceTripterygium wilfordii polyglycosides (TWP), extracted from the traditional Chinese herb Tripterygium wilfordii, has been widely used in the treatment of rheumatoid arthritis (RA). However, the toxicity of TWP to a variety of organs such as liver, kidney and testis greatly limits its clinical application. Salvia miltiorrhiza Bunge is often used in the treatment of RA due to its blood circulation promoting, stasis resolving, and anti-inflammatory effects. Salvia miltiorrhiza Bunge has also been reported to possess multiple organ protective effects. Aim of the studyTo investigate the influences of two main components of Salviorrhiza miltiorrhiza Bunge, hydrophilic salvianolic acids (SA) and lipophilic tanshinones (Tan), on the efficacy and toxicity of TWP in treating RA and to explore the underlying mechanisms. Materials and methodsSA and Tan were extracted from Salvia miltiorrhiza Bunge and the extracts were quantitated by HPLC and identified by UPLC-Q/TOF-MS. Then, a collagen-induced arthritis (CIA) rat model was established using bovine type II collagen (CII) and incomplete Freund's adjuvant (IFA). CIA rats were treated with TWP and/or SA/Tan. After 21 days of continuous treatment, arthritis symptoms and organs toxicity were evaluated. Meanwhile, serum metabolomics were investigated by the UPLC-Q/TOF-MS to understand the underlying mechanism. ResultsSA and Tan extracts could significantly alleviate arthritis symptoms in CIA rats and decrease the serum levels of inflammatory factors TNF-α, IL-1β and IL-6 when combined with TWP. Meanwhile, both extracts alleviated injury of liver, kidney and testis caused by TWP, and the hydrophilic extract SA was superior. Moreover, a total of 38 endogenous differential metabolites were identified between the CIA model group and the TWP group, among which 33 metabolites were significantly recovered after the combination of SA or Tan. Metabolic pathway analysis showed that SA and Tan can affect metabolic pathways including linoleic acid metabolism, glycerophospholipid metabolism, sphingolipid metabolism and steroid biosynthesis metabolism pathway. ConclusionsOur findings indicated for the first time that two Salviorrhiza miltiorrhiza Bunge extracts could improve the efficacy and reduce the toxicity of TWP in the treatment of RA by adjusting metabolic pathways, and the hydrophilic extract SA was superior.

Comparison of conventional Doppler imaging techniques and superb microvascular imaging in determination of vascularization in undescended testes.

Our aim was to gain an idea about testicular injury by comparing the reduced volume, which is one of the indirect indicators of testicular damage in undescended testes, and by evaluating the reduced microvascular blood flow by superb microvascular imaging, and also to determine whether superb microvascular imaging modes could detect microvascular blood flow in more detail in the decreased volume of undescended testes. We compared testicular blood flow in undescended testes via conventional Doppler imaging, color superb microvascular imaging, and monochrome superb microvascular imaging techniques with contralateral normally located testis and normal control group. Each sample of testicular tissue was evaluated using a qualitative method. Spot color encoding and linear flow color encoding counts determined in testicular parenchyma were counted separately and expressed as numerical data. The localization of the examined testes in the grayscale was noted (proximal inguinal canal, medial inguinal canal, distal inguinal canal, and scrotal). The volume of undescended testes was calculated automatically via a formula for volume. Monochrome superb microvascular imaging is significantly superior in visualizing the vascularity of undescended testes compared with color Doppler, power Doppler and color superb microvascular imaging (p = 0.001). Also, undescended testes have a significantly lower blood flow compared with contralateral normal testes (p = 0.001). The volume of undescended testes was significantly lower than the contralateral normal testes. The volume, structure and blood flow are indirect signs of testicular damage in undescended testes. Monochrome superb microvascular imaging can detect vascularity in undescended testes better than the conventional Doppler imaging technique and color superb microvascular imaging. Based on our findings, we can report that monochrome superb microvascular imaging can be used to evaluate testicular injury and vascularity of undescended testes.

Difenoconazole Exposure Induces Retinoic Acid Signaling Dysregulation and Testicular Injury in Mice Testes.

Difenoconazole (DFZ) is a broad-spectrum triazole fungicide that is widely utilized in agriculture. Although DFZ has been demonstrated to induce reproductive toxicity in aquatic species, its toxic effects on the mammalian reproductive system have yet to be fully elucidated. In vivo, male mice were administered 0, 20 or 40 mg/kg/d of DFZ via oral gavage for 35 days. Consequently, DFZ significantly decreased testicular organ coefficient, sperm count and testosterone levels, augmented sperm malformation rates, and elicited histopathological alterations in testes. TUNEL assay showed increased apoptosis in testis. Western blotting results suggested abnormally high expression of the sperm meiosis-associated proteins STRA8 and SCP3. The concentrations of retinoic acid (RA), retinaldehyde (RE), and retinol (ROL) were increased in the testicular tissues of DFZ-treated groups. The mRNA expression level of genes implicated in RA synthesis significantly increased while genes involved in RA catabolism significantly decreased. In vitro, DFZ reduced cell viability and increased RA, RE, and ROL levels in GC-2 cells. Transcriptome analysis revealed a significant enrichment of numerous terms associated with the RA pathway and apoptosis. The qPCR experiment verified the transcriptome results. In conclusion, our results indicate that DFZ exposure can disrupt RA signaling pathway homeostasis, and induce testicular injury in mice testes.

RhoGDIα regulates spermatogenesis through Rac1/cofilin/F-actin signaling

Spermatogenesis is an extremely complex process, and any obstruction can cause male infertility. RhoGDIα has been identified as a risk of male sterility. In this study, we generate RhoGDIα knockout mice, and find that the males have severely low fertility. The testes from RhoGDIα−/− mice are smaller than that in WT mice. The numbers of spermatogonia and spermatocytes are decreased in RhoGDIα−/− testis. Spermatogenesis is compromised, and spermatocyte meiosis is arrested at zygotene stage in RhoGDIα−/− mice. Acrosome dysplasia is also observed in sperms of the mutant mice. At the molecular level, RhoGDIα deficiency activate the LIMK/cofilin signaling pathway, inhibiting F-actin depolymerization, impairing testis and inducing low fertility in mouse. In addition, the treatment of RhoGDIα−/− mice with Rac1 inhibitor NSC23766 alleviate testis injury and improve sperm quality by inhibiting the LIMK/cofilin/F-actin pathway during spermatogenesis. Together, these findings reveal a previously unrecognized RhoGDIα/Rac1/F-actin-dependent mechanism involved in spermatogenesis and male fertility.

The effects of boron on oxidative stress, reproductive parameters, and DNA damage in testicular tissue in wistar rats on a fatty diet

This study aimed to investigate the protective effect of boron (B) against fat diet (FD)-induced spermatological, histopathological, biochemical and DNA damage in Wistar Albino Rats. Male rats were divided into five groups; the control group was fed a normal diet, the FD group was fed a normal diet with 40% beef tallow the FD+B5 group was fed a fat diet containing 5 mg/kg/daily boron, the FD+B10 group was fed a fat diet containing 10 mg/kg/daily boron, and the FD+B20 group was fed a fat diet containing 20 mg/kg/daily boron. The spermatozoon motility, membrane integrity and glutathione (GSH) level increased in the rats' testicular tissue in the groups given B. Conversely, the abnormal sperm rate, malondialdehyde (MDA) level and DNA damage were high in the FD group. Histopathologically, it was observed that decreased spermatozoa concentration in tubules seminiferous contortus lumen in FD and FD+B5 groups. FD+B10 administration reversed FD-induced spermatological parameters, MDA level and DNA damage in the rats' testes. These results indicated that boron protects spermatological parameters and repairs DNA damage, reduces FD-induced high MDA levels, enhances the antioxidant defense system and eliminates tissue injury in rats' testes.

Oct4 reduction contributes to testicular injury of unilateral testicular torsion in mice model and apoptotic death of Sertoli cells through mediating CIP2A expression

This study explored the mechanism of ipsilateral testis injury after ipsilateral testicular torsion detorsion (T/D) and the potential testis-protective part of the octamer-binding transcription factor 4 (Oct4)-cancerous inhibitors of protein phosphatase 2A (CIP2A) axis in a T/D animal model and in ischemia–reperfusion (IR)-treated testicular Sertoli TM4 cells. Quantitative Polymerase chain reaction (PCR) and western blot (WB) confirmed the downregulation of both CIP2A and Oct4 expression in the testicular tissue from T/D mice compared with sham-operated mice. T/D model was then established in mice with upregulated Oct4 expression in the testis. Oct4 elevation restored CIP2A expression in testes after T/D treatment. Furthermore, we observed that an increase in Oct4 ameliorated the testicular damage caused by torsion in the testis. Biochemical analysis indicated that T/D treatment increased serum anti-sperm antibody levels, but reduced testosterone levels. Meanwhile, in testicular tissue, reactive oxygen species (ROS), malondialdehyde (MDA), and activity of testicular myeloperoxidase (MPO) enzymes were promoted, while glutathione peroxidase activity (GPx) was decreased by T/D injury. Notably, testicular Oct4 restoration partially counteracted the effect of T/D treatment on these biochemical indices. Hypoxia/reoxygenation (HR) treatment was applied to TM4 cells to mimic TT injury in vitro. A gain-of-function study showed that Oct4 overexpression partly counteracted the promoting role of HR in cell damage, apoptosis, and oxidative stress in TM4 cells. These observations provide novel insights into the possible biochemical mechanism underlying the mediation of the Oct4-CIP2A axis in T/D injury.

Integration of metabolomics and transcriptomics to reveal ferroptosis is involved in Tripterygium wilfordii polyglycoside tablet-induced testicular injury

Ethnopharmacological relevanceTripterygium wilfordii polyglycoside tablet (TWP), a traditional Chinese medicine preparation, has multiple pharmacological properties, including anti-inflammatory, immune-modulatory and anti-proliferative activities. However, the reproductive toxicity of TWP greatly limits its clinical application and the mechanism of TWP-induced reproductive toxicity is not fully understood yet. Aim of the studyThis study was designed to explore the mechanism of TWP-induced testis injury in male rats. Materials and methodsThe mechanism underlying TWP-induced rat testicular injury was firstly investigated by integration of metabolomics and transcriptomics. Meanwhile, histopathological analysis, Western blot and RT-qPCR were performed to confirm the damaging effects and mechanisms of TWP on rat testis. ResultsHistopathological analysis revealed that TWP had significant testicular damage, which severely reduced the testis's tubular diameter and epithelium height. Further, TWP caused the protein level of ZO-1, CLDN11, PLZF, and OCT4 significantly downregulate, suggesting the blood-testis barrier function and spermatogenesis were damaged. Differentially expressed genes (DEGs), including 4952 upregulated and 2626 downregulated, were found in TWP-exposed testis compared to the normal group. Moreover, 77 changed metabolites were identified from testis samples. With integrated analysis of DEGs and changed metabolites, we found that glutathione metabolism and ferroptosis played an essential role in testicular injury. Additionally, the levels of ferroptosis-related protein GPX4, SLC7A11, and NRF2 were significantly downregulated, and the protein level of 4-HNE, a leading product of lipid peroxidation and oxidative stress, was upregulated. The changes in ferroptosis-related genes indicated that TWP might promote ferroptosis in rat testis. ConclusionThese results suggested that ferroptosis was involved in the testicular damage caused by TWP, which might provide a new strategy to alleviate TWP- induced testicular injury.

Selenium alleviates cadmium-induced oxidative stress, endoplasmic reticulum stress and programmed necrosis in chicken testes

Cadmium (Cd) is a common heavy metal pollutant, and one of the important target organs of its toxicity is the testis. Selenium (Se) has the ability to antagonize the toxicity of Cd. However, the mechanism of the alleviating effects of Se on Cd in chicken testis injury through oxidative stress, endoplasmic reticulum stress (ERS), and programmed necrosis remained unclear. To explore this, 80 7-day-old chickens were divided into the Control group, the Se group (1.00 mg/kg Se), the Cd group (150.00 mg/kg Cd), and the CdSe group. On the 30th and 60th days, serum and chicken testis tissue samples were collected for testing. The results showed that Cd exposure resulted in swelling and deformation of seminiferous tubules, and thinning of the seminiferous epithelium. The ROS and MDA increased, and the SOD, CAT, GSH, GSH-Px decreased. The expression of GRP78, PERK, IRE1, ATF6, CHOP, and JNK in the Cd group increased. The expression of TNF-α, TNFR1, RIP1, RIP3, MLKL, and PARP1 increased, while the expression of Caspase-8 decreased. Histopathological changes, oxidative stress, ERS, and programmed necrosis were improved after CdSe treatment. In conclusion, Se antagonized the toxicity of Cd, and Se could alleviate Cd-induced oxidative stress, ERS, and programmed necrosis in chicken testis.

Integrative proteomics and metabolomics approach to identify the key roles of icariin-mediated protective effects against cyclophosphamide-induced spermatogenesis dysfunction in mice.

The alkylating antineoplastic agent cyclophosphamide (CP) is known to be toxic to the male reproductive system, but there are no effective prevention or treatment options. The flavonoid icariin (ICA), which is used in Chinese medicine, has been shown to have a number of biological functions, including testicular protection. The current study looked into the protective effects of ICA in preventing CP-induced spermatogenesis dysfunction. The current study looked into the role of ICA in preventing testicular dysfunction caused by CP. For 5days, healthy adult mice were given saline or a single dose of CP (50mg/kg) intraperitoneally (i.p). For the next 30days, mice were given ICA (80mg/kg) by gavage. Animals were euthanized 12h after receiving ICA, and testes were removed for biochemical, histopathological, sperm evaluation, and transmission electron microscope analysis (TEM). We also investigated the potential biological effects of ICA on CP-induced spermatogenesis dysfunction in mice using an integrated proteomic and metabolomic approach. The levels of 8309 proteins and 600 metabolites were measured. The majority of the differential proteins and metabolites were found to be enriched in a variety of metabolic pathways, including the PI3K-Akt signaling pathway, necroptosis, the mTOR signaling pathway, glycerophospholipid metabolism, and ABC transporters, implying that ICA may have molecular mechanisms that contribute to CP-induced spermatogenesis dysfunction in the testis. Taken together, these findings show that ICA effectively reduces testis injury, implying that ICA may have a role in male infertility preservation.

Hadh deficiency induced oligoasthenoteratozoospermia through the TNF-α/Bcl-2 pathway in male mice.

The process of spermatogenesis is a complex and delicate process that is still not fully understood. In this study, we examined the role of fatty acid oxidase 3-hydroxy acyl CoA dehydrogenase (HADH) in maintaining normal spermatogenesis in mice. In male mice, ablation of the Hadh gene using CRISPR/Cas9 technology arrested spermatocyte meiosis, increased multinucleated giant germ cells and vacuoles in seminiferous tubules, and accompanied with acrosomal dysplasia. Hadh-/- male mice showed the typical features of oligoasthenoteratozoospermia (OAT), including decreased sperm concentration and motility and increased sperm abnormalities. Next, we explored the molecular events in the testes of the mutant mice. We found fatty acids accumulated in the testis of Hadh-/- mice. And also, inflammatory factors TNF-α, IL-1β, and IL-6 were significantly increased, apoptosis-related protein Bcl-2 was decreased, and Bax and cleaved-Caspase3 were increased in Hadh-/- male mice testis. After using etanercept, a specific inhibitor of TNF-α, testis injury caused by Hadh knockout was significantly alleviated, the sperm quality and motility were improved, and germ cell apoptosis was reduced. So our study demonstrated that Hadh deletion caused an increase in fatty acids. The accumulated fatty acids further induced testicular inflammation and germ cell apoptosis through the TNF-α/Bcl-2 signaling pathway, finally resulting in OAT in the Hadh-/- mice. Inhibiting TNF-α may be used as a new treatment approach for testicular inflammation and OAT.

Utility of melatonin in mitigating ionizing radiation-induced testis injury through synergistic interdependence of its biological properties

BackgroundIonizing radiations (IR) have widespread useful applications in our daily life; however, they have unfavorable effects on reproductive health. Maintaining testicular health following IR exposure is an important requirement for reproductive potential. The current study explored the role of melatonin (MLT) in mitigating IR-induced injury in young adult rat testis.MethodsRats were given daily MLT (25 mg/kg) for 3 and 14 days after receiving 4 Gy γ-radiation.ResultsSerum MLT levels and other antioxidants, including glutathione content, and the activity of glutathione peroxidase and glutathione reductase in the testis of the irradiated rats were remarkably maintained by MLT administration in irradiated rats. Hence, the hydrogen peroxide level declined with remarkably reduced formation of oxidative stress markers, 4-hydroxynonenal, and 8-Hydroxy-2′-deoxyguanosine in the testis of irradiated animals after MLT administration. The redox status improvement caused a remarkable regression of proapoptotic protein (p53, Cyto-c, and caspase-3) in the testis and improved inflammatory cytokines (CRP and IL-6), and anti-inflammatory cytokine (interleukin IL-10) in serum. This is associated with restoration of disturbed sex hormonal balance, androgen receptor upregulation, and testicular cell proliferation activity in irradiated rats, explaining the improvement of sperm parameters (count, motility, viability, and deformation). Consequently, spermatogenic cell depletion and decreased seminiferous tubule diameter and perimeter were attenuated by MLT treatment post irradiation. Moreover, the testis of irradiated-MLT-treated rats showed well-organized histological architecture and normal sperm morphology.ConclusionsThese results show that radiation-induced testicular injury is mitigated following IR exposure through synergistic interdependence between the antioxidant, anti-inflammatory, anti-apoptotic, and anti-DNA damage actions of MLT.

10-7M genistein partially alleviates 10-7M MEHP unfavorable effects in a new modified fetal rat testis culture system.

Background: Recent studies revealed that some common endocrine-disrupting chemicals (EDCs) including phthalates and phytoestrogens may exhibit low-dose effects properties. However, how low dose of these EDCs and their mixture would affect fetal rat testis development still needs further investigation. Moreover, testis organ culture system also needs further modification to provide an effective tool for ex vivo EDCs study. Methods: We firstly modified the agarose organ culture system, in which fetal rat testes were cultured for 4 days (d1 to d4) on agarose gels held by Millicell inserts. Then we used the modified agarose culture system to study the combined effects of multiple EDCs exposure. 15.5 dpc fetal rat testes were isolated and treated with vehicle, MEHP (0.1 μmol/L), GEN (0.1 μmol/L) or MEHP (0.1 μmol/L) + GEN (0.1 μmol/L). Parameters concerning testicular cell development and function were evaluated, trying to gain insight into the early molecular events after multiple EDCs exposure. Results: The development of somatic, germ cells and seminiferous tubule in 15.5 dpc fetal rat testis was better sustained in the modified agarose culture system. Based on the modified system, we found that MEHP at 0.1 μmol/L induced alterations in gonocyte markers, antioxidative enzyme activity as well as transient reduction of testosterone production, accompanied by mitochondria swelling in gonocytes and Sertoli cells. No obvious morphological and histological alterations were observed in all treated groups. However, coadministration of genistein at 0.1 μmol/L partially alleviated MEHP-induced fetal testis damage ex vivo through enhancement of antioxidative action. MEHP at low dose still showed weak endocrine disrupting properties but did not exhibit typical low-dose effects. Conclusion: Our findings indicated that the modified agarose culture system could better mimic testicular microenvironment without obvious hypoxic cell damage. Furthermore, low dose of MEHP induced mild disruption to fetal testis development, cotreatment of genistein at low dose attenuated MEHP induced fetal testis injuries in part by balancing redox state, indicating that low dose of genistein may partially protect fetal testis from phthalates induced injury.

Lycopene modulates hepatic toxicity and testicular injury induced by etoposide in male rats

Lycopene (C40H56), a carotenoid found in red colour fruits, is known as a powerful antioxidant that protects cells from damage caused by reactive oxygen species (ROS). Etoposide inhibits topoisomerase II activity and restricts the development of cancer cells, though it establishes oxidative stress. To study the effect of lycopene (Ly) against hepatotoxicity and testis injury induced by etoposide in male rats. Forty male Wister albino rats. The experiment lasted for seven consecutive weeks including one week as acclimatization time. The experiment was in a completely randomized design with a 2×2 factorial arrangement. The animals were grouped as follow: No etoposide injection and no lycopene (control), lycopene supplementation (LY), etoposide injection (ET), and rats with etoposide injection and lycopene supplement (ET+LY). At the end of the experiment, rats were sacrificed by cervical dislocation. Blood samples were harvested and analyzed for serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), low-density lipoprotein-Cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), total cholesterol (TC), Total Protein (TP), glucose (GLU) and testosterone. The left testis was manipulated for histological examination. The result of experiment showed that rats with etoposide injection had higher ALT, AST, and ALP than the control rats. In contrast co-treated rats (ET+LY) significantly modulated the levels of the hepatic parameters. Administration of lycopene increased testosterone concentration and germinal epithelium of seminiferous tubules in testes rats. Lycopene might be a promising agent with hepatoprotective effect in restoring testis injury induced by etoposide in rats.

The alterations of blood-testis barrier in experimental testicular ınjury models

The blood-testis barrier is found between the Sertoli cells and divides the seminiferous tubule epithelium into basal and adluminal compartments. The germinal cell renewal, differentiation and cell cycle progression up to the preleptotene spermatocytes stage take place in the basal compartment, however, meiosis, spermiogenesis and spermiation take place in the adluminal compertment. The blood-testis barrier consists of tight junctions as well as ectoplasmic specialisations, desmosomes and gap junctions to create specific microenvironment for the completion of spermatogenesis to form spermatozoa. The blood-testis barrier is not a static ultrastructure, it undergoes extensive restructuring during the seminiferous tubule epithelial cycle of spermatogenesis to allow the transit of preleptotene spermotocytes at the blood-testis barrier from basal compartment towards the adluminal compartment. The functions of the blood-testis barrier include preventing the transport of biomolecules into the paracellular space, forming an immunological barrier, separating cellular processes during the spermatogenic epithelial cycle, and establishing the cellular polarity of the seminiferous tubule. However, various environmental conditions, chemotherapeutic agents, toxic substances and lifestyle have degenerative effects on blood-testis barrier, resulting in testicular damage, altered sperm parameters and ultimately male infertility. The alterations in morphological and molecular organization of blood-testis barrier in different experimentally induced testis injury models are reviewed in this article.

Protective mechanism of selenium on mercuric chloride-induced testis injury in chicken via p38 MAPK/ATF2/iNOS signaling pathway

Mercuric chloride (HgCl2) is a well-known toxic heavy metal contaminant, which causes male reproductive function defects. Selenium (Se) has been recognized as an effective antioxidant against heavy metals-induced male reproductive toxicity. The aim of present study was to explore the potentially protective mechanism of Se on HgCl2-induced testis injury in chicken. Firstly, the results showed that Se mitigated HgCl2-induced testicular injury through increasing the blood-testis barrier (BTB) cell-junction proteins expression of occludin, zonula occludens-1 (ZO-1), connexin 43 (Cx43), and N-cadherin. Secondly, Se alleviated HgCl2-induced oxidative stress through decreasing the malondialdehyde (MDA) content and increasing the superoxidase dismutase (SOD), glutathione peroxidase (GSH-Px) activities as well as the total antioxidant capacity (T-AOC) level. Thirdly, Se inhibited the activation of p38 MAPK signaling through decreasing the proteins expression of phosphorylated-p38 (p-p38) and phosphorylated-ATF2 (p-ATF2), and alleviated inflammation response through decreasing the proteins expression of inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NF-κB), tissue necrosis factor-alpha (TNF-α), and cyclooxygenase 2 (COX2). Collectively, these results demonstrated that Se effectively alleviated HgCl2-induced testes injury via improving antioxidant capacity to reduce inflammation mediated by p38 MAPK/ATF2/iNOS signaling pathway in chicken. Our data shed a new light on potential mechanisms of Se antagonized HgCl2-induced male reproductive toxicity.

Qiangjing tablets repair of blood-testis barrier dysfunction in rats via regulating oxidative stress and p38 MAPK pathway

BackgroundThe blood-testis barrier (BTB) is a physical barrier of the testis to prevent various exogenous substrates from entering apical compartments and provides immune privilege for spermatogenesis, which is essential for normal spermatogenic function of testis. It has been shown that oxidative stress can damage BTB by activating the p38 MAPK pathway. In Traditional Chinese Medicine, Qiangjing tablets (QJT) improve spermatogenesis and increase pregnancy rates. Previous studies have confirmed that QJT can improve sperm quality and have obvious antioxidant effects. In this study, we explore whether QJT contributes to recovery from BTB dysfunction in rats.MethodsBTB dysfunction was induced in rats by 1% Cyclophosphamide (CP). The CP-induced rats in the treatment group were given a dose of QJT (0.45 g/kg·d) by gavage. Testis tissues were collected for histopathological and biochemical analysis, and the testis weight was estimated. Levels of BTB-related proteins and antioxidant enzyme were analyzed in the testis tissues.ResultsQJT resolved the pathological injury of rats testis induced by CP. Furthermore, MDA levels were significantly reduced, and the levels of SOD markedly increased in the testicular tissue after QJT treatment. In addition, QJT down-regulated the expression of p38 protein in rat testis and up-regulated the expressions of key proteins ZO-1, occludin and F-actin in BTB.ConclusionThese results demonstrate that QJT exerts protective effects on CP-induced rats with BTB dysfunction, likely by regulating the oxidative stress-mediated p38 MAPK pathway.

Rapamycin Ameliorates Radiation-Induced Testis Damage in Mice.

Male infertility is an important problem in human and animal reproduction. The testis is the core of male reproduction, which is very sensitive to radiation. The decline of male reproductive ability is a common trend in the world. Radiation is a physical factor leading to abnormal male reproductive function. To investigate the potential mechanisms of testicular damage induced by radiation and explore effective strategies to alleviate radiation-induced testis injury, C57BL/6 mice were irradiated with 8.0 Gy of X-ray irradiation. Testis and epididymis were collected at days 1, 3, and 7 after radiation exposure to analyze spermatogonia and sperm function. The results showed that radiation significantly destroyed testicular structure and reduced the numbers of spermatogonia. These were associated with mTORC1 signaling activation, decreased cellular proliferation and increased apoptotic cells in the irradiated testis. Rapamycin significantly blocked mTORC1 signaling pathway in the irradiated testis. Inhibition of mTORC1 signaling pathway by rapamycin treatment after radiation could significantly improve cell proliferation in testis and alleviate radiation-induced testicular injury after radiation exposure. Rapamycin treatment benefited cell survival in testis to maintain spermatogenesis cycle at 35 days after irradiation. These findings imply that rapamycin treatment can accelerate testis recovery under radiation condition through inhibiting mTORC1 signaling pathway.