Experimental Varicocele Research Articles

Experimental Varicocele Impairs DNA Methylation and Demethylation in Germ Cells, TESE, and Epididymal Spermatozoa, Impacting Active DNA Demethylation in Zygotes.

Varicocele causes infertility. The current study has investigated the impact of experimental varicocele on DNA methylation, demethylation, and damage in the germ cells, TESE-derived and epididymal spermatozoa. Moreover, the results were compared between epidydimal and TESE-derived spermatozoa. Finally, the varicocele-induced effect on active DNA demethylation (ADD) of male pronucleus and pre-implantation embryo development was assessed. The mature male rats were divided into control, control-sham (undergone simple laparotomy), and experimental varicocele-induced groups (n = 6/each group). The left renal vein semi-ligation was considered to induce varicocele. The expression levels of DNA methyltransferase 1 (DNMT1) and ten-eleven-translocation proteins (TET1, 2, 3), and global DNA methylation in testicular tissue, TESE, and epididymis-derived spermatozoa, and the ADD in zygotes male pronucleus as well as pre-implantation embryo development were assessed. The expression levels of DNMT1 and TET1, 2, 3 in testicles, TESE, and epididymis-derived spermatozoa were decreased in the varicocele group compared to the control and control-sham groups. The TESE-derived spermatozoa exhibited higher DNMT1, higher DNMT1, and TET 1, 2, and no change in TET3 expression compared to epididymis-derived spermatozoa. The varicocele group represented lower DNA methylation in the testicles, TESE-derived and epididymal spermatozoa, higher 5mC+ signal in male pronucleus, and a lower pre-implantation embryo development compared to control and control-sham rats. The TESE-derived spermatozoa exhibited higher 5mC protein expression compared to epididymal spermatozoa. In conclusion, varicocele can negatively impact the DNA methylation/demethylation processes impairing spermatogenesis and leading to fertilization failure, which may ultimately result in a decrease in embryo development by increasing susceptibility to DNA damage.

Moment of induction and duration of experimental varicocele in rats: effects on semen quality.

Varicocele is a condition known to cause damage to seminal parameters and sperm function. Furthermore, it has been hypothesized that the varicocele effect on fertility is time-dependent; however, little is known about the consequences of its establishment time on reproductive organs and/or sperm function. This study aimed to evaluate the effect of the duration of experimental varicocele on reproductive organs, sperm parameters, and sperm function. Varicocele induction surgeries were performed in Wistar rats aged 40 or 100 days old. At 160-day-old, analyses were performed, including biometry of reproductive organs (prostate, seminal vesicles, epididymis, and testis), sperm parameters (vitality, morphology, and motility), and sperm function tests (nuclear DNA integrity, acrosome integrity, and mitochondrial activity). The analysis of the biometry of reproductive organs showed no differences between distinct ages in which varicocele was induced. The total abnormal sperm morphology was bigger in animals with varicocele induced to 100 days old than in animals with varicocele induced to 40 days old. Regarding nuclear DNA integrity, animals of varicocele induced to 100 days old showed worse results compared to animals of varicocele induced to 40 days old. Other parameters analyzed showed no differences between varicocele groups. In this study conducted on rats, we conclude that varicocele adversely affects sperm, particularly its function. However, we did not observe a negative progressive effect on sperm.

Shugan Tongluo Qiangjing recipe protects against varicocele of EVC rats through modulating sperm DNA damage, telomere expression and oxidative stress

Varicocele (VC) refers to expansion and tortuosity of spreading venous plexus in spermatic cord due to poor blood flow. This study aimed to investigate effects of Shugan Tongluo Qiangjing recipe (SGTL) on sperm DNA damage and oxidative stress in experimental VC (EVC) rats. EVC model was established by partial ligation of left renal vein. Spermatic vein diameter, testicular weight, sperm DNA fragmentation index (DFI) were evaluated. Telomere reverse transcriptase (TERT) expression, telomere gene transcription, and testicular tissue morphology were determined·H2O2, catalase, SOD, T-AOC were measured with colorimetry. SGTL significantly decreased spermatic vein diameter (P=0.000) and increased testicular weight (P=0.013) of rats compared those of EVC rats. SGTL maintained testicular tissue morphology in EVC rats. SGTL markedly reduced sperm DFI value in sperm of rats compared to EVC rats (P=0.000). SGTL significantly enhanced TERT expression and telomere gene transcription (P=0.028) in testis of rats compared to EVC rats. SGTL reduced H2O2 levels (P=0.001) and promoted CAT activity (P=0.016), SOD activity (P=0.049), and T-AOC activity (P=0.047) of rats, compared to EVC rats. In conclusion, SGTL could reduce pathogenic process of EVC by reducing sperm DNA damage and regulating telomere length in EVC rats, which may be related to oxidative stress regulation.

Effect of vitamin D in experimental varicocele model in rats

Purpose: Varicocele is a pathological condition that affects approximately 20% of adult men, causing infertility and sperm deterioration. The aim of our study was to investigate the efficacy of vitamin D (Vit. D) in the pathophysiology of varicocele. We performed biochemical, gene expression analyses and histopathological to evaluate the efficacy of vitamin D in the experimental varicocele model.
 Materials and Methods: In the study, 30 adult male Wistar Albino rats were used. The rats were divided into 3 groups equally as control group, experimental group (varicocele), treatment group (varicocele + D vit.). The treatment group received 500 IU/kg D vit. intramuscularly.
 Results: Histopathological, TRPM2-8 gene expression and biochemical analyses were performed on testicular and blood samples collected at the end of the experiment. The experimental group showed a deterioration in tubular structure, a decrease in total antioxidant levels and an increase in total oxidant levels. The treatment group, on the other hand, showed an increase in TAS, a decrease in TOS and a beneficial improvement in tubular structure disorders. Analysis of gene expression levels showed that TRPM2-8 expression levels were significantly increased in the varicocele group and decreased in the treatment group.
 Conclusion: In the varicocele model, the use of vitamin D had a significant effect on TRPM2-8 gene level, pathological seminiferous tubules and biochemical values. Further studies are needed to determine the clinical application of vitamin D in varicocele disease.

Protective Effect of Anthocyanin on Testicular Damage and Oxidative Stress Induced by Experimental Varicocele in Adult Rats: A Histological and Biochemical Study

Protective Effect of Anthocyanin on Testicular Damage and Oxidative Stress Induced by Experimental Varicocele in Adult Rats: A Histological and Biochemical Study

Positive Effects of the Nutraceutical Association of Lycopene and Selenium in Experimental Varicocele.

Many natural substances commonly found in healthy diets have been studied for their potential to reduce male infertility associated with varicocele. A positive role of selenium (Se) or lycopene alone was demonstrated in experimental varicocele, while no data are available on their association. One group of male Sprague-Dawley rats was sham operated and daily treated with Se (3 mg/kg, i.p.), lycopene (1 mg/kg, i.p.), or their association. A second group underwent surgery to induce varicocele. Sham and half of the varicocele animals were sacrificed after twenty-eight days, while the residual animals were treated for one more month and then sacrificed. In varicocele animals, testosterone levels and testes weight were reduced, Hypoxia Inducible Factor-1α (HIF-1α) expression was absent in the tubules and increased in Leydig cells, caspare-3 was increased, seminiferous epithelium showed evident structural changes, and many apoptotic germ cells were demonstrated with TUNEL assay. The treatment with lycopene or Se alone significantly increased testis weight and testosterone levels, reduced apoptosis and caspase-3 expression, improved the tubular organization, decreased HIF-1α positivity of Leydig cells, and restored its tubular positivity. Lycopene or Se association showed a better influence on all biochemical and morphological parameters. Therefore, the nutraceutical association of lycopene plus Se might be considered a possible therapeutic tool, together with surgery, in the treatment of male infertility. However, long-term experimental and clinical studies are necessary to evaluate sperm quantity and quality.

The time course of nod-like receptor family pyrin domain containing 3 inflammasome complex expressions in the testis tissue of an experimental varicocele rat model: An experimental study.

Varicocele is characterized by abnormal dilation of the testicular vein, which results in hypoxia, the accumulation of reactive oxygen species, and the production of proinflammatory cytokines. It seems that a group of cytosolic receptors named nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, is activated and involved in the pathogenesis of varicocele. We aim to determine the time course of NLRP3 inflammasome expression in the testis tissue following varicocele induction. In this experimental study, 36 adult Wistar rats (8 wk, 200-250 gr) were used. For the varicocele induction, the left renal vein was partially ligated. The mRNA levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, and caspase-1 were evaluated by real-time polymerase chain reaction at 1, 2, 4, 8, and 12 wk after varicocele induction. Results showed that the gene expression of NLRP3 inflammasome component including NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, and caspase-1 did not alter during week 1, 2, 4, and 8 after operation (p = 0.09). 12 wk after varicocele induction, gene expression levels were significantly up-regulated (p = 0.02). Our data provides clear evidence that varicocele stimulates inflammasome activation in the testis tissue 12 wk after the operation, and this time is required for investigating NLRP3 activity in the varicocele rat model.

Resveratrol ameliorates spermatogenesis by increasing protamine 1, 2 and HSPA2 expression in experimental varicocele rat model

ObjectivesVaricocele is a common cause of male infertility associated with an elevated testicular temperature that induces apoptosis, spermatogenesis dysfunction, and affects sperm parameters. In this study, we investigate the probable therapeutic effects of resveratrol (RES), a natural phytoalexin, against varicocele. Materials and methodsIn this study, 48 male Wistar rats randomly divided into 8 groups: normal, sham, normal+RES (20 and 50mg/kg), varicocele, varicocele+ethanol and varicocele+RES (20 and 50mg/kg). Incomplete closure of the left renal vein was used for varicocele induction and two months later, RES was administrated orally for 60 days. Then, sperm parameters, DNA fragmentations, chromatin density, and testis histopathology were analyzed. In addition, HSPA2, protamine 1, and 2 expression levels were evaluated using real-time PCR. ResultsAccording to our results, resveratrol treatment improved sperm parameters, testis histopathology, DNA fragmentation, and chromatin maturation which damaged follow varicocele (p≤0.05). Also, it increased HSPA2, protamine 1, and 2 expression levels significantly in both doses (p≤0.05). ConclusionResveratrol potentially attenuates varicocele-induced spermatogenic impairments by its antioxidant features and regulates spermatogenic gene expression undergoing DNA fragmentation, so leads histopathological properties of tissues to physiological parameters.

Zishen Yutai Pill improves sperm quality and reduces testicular inflammation in experimental varicocele rats

ObjectiveZishen Yutai Pill (ZYP), containing 15 Chinese traditional medicine, is a safe and well quality-controlled TCM preparation with promising effects in many fields of reproduction. The current study was designed to investigate the therapeutic effects of ZYP on sperm quality and testis in varicocele (VC) rats. Materials and methodsMale Wistar rats were randomly divided into four groups (n = 6), i.e., a sham group, a VC group, and VC groups treated with different dose of ZYP (1575 and 3150 mg/kg/d, respectively). The experimental VC model was established by partial ligation of left renal vein. Six weeks after model establishment, ZYP was orally administered once a day for the next 6 weeks. Parameters relating to testis and sperm quality were assessed. Hematoxylin–eosin staining was used to showed testicular tissue damage in experimental VC rats. Expressions of proteins relating to NLRP3 inflammasome pathways were determined using Western blot (WB). The mRNA expressions of relating genes were determined using quantitative real-time PCR (qRT-PCR) analysis. ResultsZYP could significantly improve sperm motility and decrease sperm DNA fragmentation index in VC rats (P < 0.05). Hematoxylin-eosin (HE) staining showed that ZYP could alleviate testicular tissue damage caused by experimental varicocele in rats. Compared to the VC model, expressions of NLRP3, ASC, and caspase-1 in rats treated with ZYP were significantly down-regulated, as validated by both qRT-PCR and WB analysis (P < 0.05). ConclusionsIn brief, ZYP could improve sperm DNA integrity by inhibiting the NLRP3 inflammasome pathway and alleviating the chronic inflammation of testicular tissue induced by experimental varicocele in rats.

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.

Retracted: Silencing CAMK2D Promotes the Proliferation of Spermatogonia in the Testis of Experimental Varicocele Rats.

[This retracts the article DOI: 10.1155/2022/7121245.].

Beneficial effects of combination therapy with testosterone and hydrogen sulfide by reducing oxidative stress and apoptosis: Rat experimental varicocele model.

Despite the effectiveness of testosterone therapy in conditions associated with testosterone deficiency, including varicocele, several dose-dependent side effects limit the clinical use of testosterone therapy. Hydrogen sulfide, a toxic gas in high concentrations but a beneficial molecule in low concentrations, acts as both a major effector and an important inducer of testosterone. This study investigated whether a subeffective dose of testosterone combined with a subeffective dose of hydrogen sulfide donor sodium hydrosulfide (NaHS) can be effective in an experimental varicocele model through a possible additive effect. Thirty Wistar rats weighing 200-250 gr were divided into 5 groups as (n = 6/each): sham, varicocele, testosterone (200 µg/kg, 5 times per wk for 4 consecutive weeks), NaHS (15 μmol/L, daily for 4 consecutive wk) and testosterone + NaHS (200 µg/kg, 5 times per wk + 15 μmol/L, daily, both for 4 consecutive wk). All animals, except in the sham group, underwent varicocele induction. The coadministration of testosterone and NaHS significantly increased serum testosterone (10.23 0.95, p = 0.01), testicular H2S levels (608.94 21.09, p 0.001), and testicular superoxide dismutase activity (66.14 1.56, p 0.001), decreased malondialdehyde levels (0.77 0.52, p 0.001), and B-cell lymphoma 2-associated X protein to B-cell lymphoma 2 (0.16 0.01, p 0.001) protein expression ratio in the testicular tissues and improved sperm parameters and testicular histopathology compared to the varicocele group. The combination therapy of subeffective doses of testosterone and NaHS can attenuate the varicocele-induced damages by reducing testicular oxidative stress and apoptosis and thus can be considered an effective approach with fewer side effects.

Silencing CAMK2D Promotes the Proliferation of Spermatogonia in the Testis of Experimental Varicocele Rats.

Varicocele is regarded as the main factor that contributes to male infertility. This study aimed to explore the effect of CAMK2D on spermatogonia in the testis of experimental varicocele rats. The experimental varicocele model was established in rats and treated using different ligation methods. mRNA expression profile analysis was performed on the left testicular tissue isolated from different groups, and differentially expressed genes (DEGs) were analysed by bioinformatics methods and identified by qRT-PCR. The effect of CAMK2D, the screened DEG, on the proliferation of spermatogonia was evaluated by CCK-8 assay. The expression level of the c-kit was measured by the immunofluorescence assay and the expression levels of CAMKII, FOXO1, and β-catenin were detected by qRT-PCR and western blotting. Five DEGs (i.e., TMCC3, FLNB, CAMK2D, OPLAH, and EGR1) were screened using the comprehensive analysis of mRNA high-throughput sequencing data. TMCC3 and FLNB were significantly downregulated, and CAMK2D, OPLAH, and EGR1 were dramatically upregulated in the testicular tissue of varicocele rats. The target DEG CAMK2D was obtained through identification by using qRT-PCR. In vitro assays revealed that the proliferation of spermatogonia was significantly facilitated by the silencing of CAMK2D, which resulted in the downregulation of CAMKII, FOXO1, and β-catenin. In conclusion, silencing CAMK2D facilitated the proliferation of spermatogonia in the testis of experimental varicocele rats.

Resveratrol benefits on sperm DNA, chromatin structure and reproductive outcomes of varicocelized rats.

In varicocele, the main cause of sperm DNA damage is oxidative stress (OS). Resveratrol, a polyphenol with antioxidant properties, can protect cells from injuries caused by OS. We investigated the benefits of resveratrol against reproductive damage caused by experimental varicocele induced from peripuberty. Eighty peripubertal male rats were distributed into 4groups: sham-control (S), varicocele (V), resveratrol (R) and varicocele treated with resveratrol (VR). Varicocele was induced through the partial ligature of the left renal vein. Resveratrol was given in a daily dose of 300mg/kg body weight (gavage). Sperm samples were collected at 100days of age for vitality, DNA fragmentation and chromatin protamination evaluations. OS analyses were carried out. Rats from all groups were mated with healthy primiparous females for evaluation of reproductive capacity and embryonic quality. The V group showed reduction of sperm vitality, altered chromatin protamination and sperm DNA integrity and high levels of OS. The VR group showed an improvement of oxidative status, sperm vitality, DNA integrity and chromatin structure, and an enhancement in the gestational index and embryonic quality. Therefore, we showed in this experimental model that resveratrol is a promising nutraceutical adjuvant and should be deeply studied to mitigate subfertility in varicocele.

Lycopene protects sperm from oxidative stress in the experimental varicocele model.

Oxidative stress (OS) is an important parameter in the evaluation of infertility caused by varicocele. Antioxidants are the most commonly prescribed drugs in these patients. Lycopene molecule, as the powerful antioxidant in the carotenoid family, has beneficial effects on improving fertility in males. Therefore, we investigated the effects of lycopene on induced OS by varicocele in an animal model. Forty‐five adult male Wistar rats were divided into two groups: control (n = 12) and varicocele (n = 33). Two months after induced varicocele, five rats in each group were sacrificed randomly and induced varicocele was investigated. Remained rats were divided into five groups (n = 7), including the control (I), varicocele (II), varicocele reserving solvent (III), varicocele reserving lycopene 4 mg/kg (IV), and 10 mg/kg (V) for two months. At the end of the experiment, intracellular reactive oxygen species (ROS), malondialdehyde (MDA), total antioxidant capacity (TAC), %DNA damage, and antioxidant enzymatic levels were measured. The results indicated that there were significant increases in the levels of ROS, MDA, DNA damage, superoxide dismutase (SOD), sperm concentration, and motility in the varicocele groups compared with the control group. In the lycopene group (10 mg/kg), sperm concentration, the levels of TAC, and catalase (CAT) activity were improved so the levels of ROS, MDA, and %DNA damage were reduced compared with varicocele group. Our findings indicated that the administration of lycopene especially at a dose of 10 mg/kg in the varicocele group could protect sperm from OS and sperm DNA damage by increasing antioxidant activity and reducing ROS.

Dracaena arborea (Dracaenaceae) Increases Sexual Hormones and Sperm Parameters, Lowers Oxidative Stress, and Ameliorates Testicular Architecture in Rats with 3 Weeks of Experimental Varicocele.

Varicocele is a disease characterized by an abnormal dilation of the pampiniform plexus that drains the testis. The main objective of this work was to evaluate the curative effects of aqueous and ethanolic extracts of Dracaena arborea on some reproductive and antioxidant markers in rats with experimental varicocele. Following varicocele induction, rats (5 per group) were randomly partitioned into untreated varicocele, vitamin E-treated (150 mg/kg), aqueous extract-treated (500 mg/kg), and ethanolic extract-treated (100 mg/kg) animals. Two other groups served as normal and sham-operated. After 2 or 4 weeks of treatments, body and sex organ weights, spermatozoa characteristics, antioxidant status, NO level, sex hormones, and testis histology were measured. Animals with 3 weeks of varicocele showed a significant (p < 0.05–0.001) decrease in body and sex organ weights, total proteins, sperm characteristics, testosterone concentration, SOD, catalase, and total peroxidase activities. An increase in the plasmatic FSH, LH, and testicular MDA and NO concentrations was also recorded. Moreover, marked disorganization of the testicular architecture was observed. Treatment with D. arborea significantly reversed these impairments due to varicocele. For instance, after 4 weeks, treatment with aqueous extract of D. arborea significantly (p < 0.05–0.001) increased testes and epididymis weights, sperm viability (89.12 ± 1.09 vs 68.22 ± 1.42), sperm density (148.50 ± 2.59 vs 110.25 ± 2.51), and sperm motility (68.16 ± 2.39 vs 55.88 ± 3.20) in the left side, compared with varicocele-untreated rats. The extract also significantly (p < 0.05–0.001) decreased malondialdehyde level (2.19 ± 0.04 vs 3.50 ± 0.13) but elevated catalase (0.97 ± 0.03 vs 0.55 ± 0.03), SOD (0.5 ± 0.03 vs 0.15 ± 0.03), and peroxidase (65.80 ± 2.9 vs 40.95 ± 2.44) activities. Present results showed that D. arborea extracts possess antioxidant effects and improve sperm quality in male rats with an existing varicocele.

LncRNA and mRNA sequencing of the left testis in experimental varicocele rats treated with Morinda officinalis polysaccharide.

Varicocele is a common disease of the male reproductive system. Morinda (M.) officinalis is a Chinese herbal medicine, whose main bioactive component M. officinalis polysaccharide (MOP) is believed to have a therapeutic effect on varicocele; however, the underlying molecular mechanisms of this effect are poorly understood. In the present study, 24 rats were randomly divided into three groups: i) Control group; ii) experimental varicocele group; and iii) 300 mg/kg MOP administration group. Analysis of mRNA and long non-coding RNA (lncRNA) expression in rat left testicular tissue was performed. The results suggested that a total of 144 mRNAs and 63 lncRNAs, 63 mRNAs and 148 lncRNAs, and 173 mRNAs and 54 lncRNAs were differentially expressed between the varicocele non-treatment and control groups, the varicocele treatment and varicocele non-treatment groups, and the varicocele treatment and control groups, respectively. Following validation by reverse transcription-quantitative PCR, the Yip1 domain family member 7 (YIPF7) gene was identified as a key mediator of varicocele pathogenesis and repair effect of MOP. Additionally, genes such as purinergic receptor P2X 4 (P2RX4), transmembrane protein 225B (TMEM255B) and Wnt family member 9B (WNT9B) were confirmed to be differentially expressed between the varicocele non-treatment and control groups. We hypothesize that TMEM255B could be a potential novel diagnostic biomarker for varicocele; WNT9B and P2RX4 likely play notable roles in the pathophysiology of the disease through the Wnt signaling pathway and regulation of transmembrane ion channels, respectively. In summary, the present study delineated the molecular mechanisms underlying varicocele pathogenesis and the therapeutic effect of MOP, identified a potential novel diagnostic marker and therapeutic target for varicocele, and provided feasible directions for further studies in the future.

Effects of Metformin on Experimental Varicocele in Rats.

The current study aimed to determine the effect of metformin (MET) on histopathologic evaluation and antioxidant enzyme activity in experimental varicocele-induced rats. A total of 60 rats were randomly divided into six experimental groups. Group 1 (control) received no medication and underwent no surgery. In group 2 (sham), the rats received no medication and the abdominal cavity was opened; however, there was no varicocele induction. In group 3 (varicocele), the abdominal cavity was opened and the rats underwent varicocele induction and received no medication. In group 4, the abdominal cavity was opened and the animals received 25 mg/kg of MET for 42 days and were varicocele-induced. Groups 5 and 6 were similar to group 4 except that the animals received 50 and 100 mg/kg of MET, respectively. At the end of the 21st and 42nd days, the rats were euthanized and the left testis was removed for histological analysis and measurement of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GPx), and total antioxidant status levels. According to the results, a dose-dependent difference was observed in testis damage grade in the MET treated groups, compared to that reported for the varicocele group (p &amp;lt;0.05). No difference was observed between 25 and 50 mg/kg of MET (P&amp;gt;0.05). Tissue MDA levels significantly increased in varicocele rats (p &amp;lt;0.05); however, MET (25, 50, and 100 mg/kg) in a dose-dependent manner decreased varicocele-induced MDA (p &amp;lt;0.05). Experimental varicocele significantly decreased SOD activity, compared to that reported for the control group (p &amp;lt;0.05). The administration of MET (25, 50, and 100 mg/kg) significantly increased tissue SOD activity in varicocele rats (p &amp;lt;0.05). The MET (25, 50, and 100 mg/kg) in a dose-dependent manner increased GPx activity in varicocele rats (p &amp;lt;0.05). There was no difference in MDA, SOD, and GPx levels between 25 and 50 mg/kg MET groups (P&amp;gt;0.05). The aforementioned findings suggested that MET treatment had beneficial effects on varicocele.

Disruption of anchoring junctions in the testes of experimental varicocele rats.

Varicocele is a common disease of the male reproductive system and is the main cause of male infertility; however, the pathological mechanisms of varicocele remain unclear. The anchoring junctions (AJs) in the testies are located between Sertoli cells, or between Sertoli cells and germ cells. Intact and functional AJs are crucial for spermatogenesis. In the present study, the histomorphology, ultrastructure of AJ, cell cycle, expression of AJ structural proteins, and the level of AJ-associated signaling molecules were investigated in the left testes of experimental varicocele rats at 8 and 12 weeks after surgery. The results revealed that varicocele induced the loss of premature germ cells from the seminiferous epithelium. Furthermore, the results of the present study also revealed damage to the AJ ultrastructure, disorientation of the spermatid head, deregulation of the cell cycle, downregulation of AJ structural proteins, enhanced phosphorylation of focal adhesion kinase (FAK) at Tyr397 and its downstream adapter Src at Tyr416, and activation of the extracellular signal-regulated protein kinase 1 (ERK1) signaling pathway. Thus, the present study demonstrated that varicocele disrupted the structure and function of AJs in the left testes of rats, and that enhancement of FAK phosphorylation may contribute to AJ damage by activating ERK1 signaling, disrupting actin-based filament networks, and altering the balance of the apical ectoplasmic specialization-blood testis barrier functional axis. These findings provide important insights into the pathological mechanisms through which varicocele contributes to male infertility and could help to identify new therapeutic targets for varicocele.

Dracaena arborea improves sperm characteristics and antioxidant enzymes in adult male rats with experimental varicocele.

Objective:We evaluated the preventive effects of aqueous and ethanolic extracts of Dracaena arborea on sperm characteristics and oxidative stress markers in adult male rats with varicocele.Methods:Thirty-six male Wistar rats were randomly distributed into 6 groups (6 animals/group) and treated for 30 days as follows: (1), normal rats receiving distilled water (10 ml/kg); (2), sham operated rats receiving distilled water (10 ml/kg); (3), varicocele rats receiving distilled water (10 ml/kg); (4), varicocele rats receiving vitamin E (150 mg/kg); (5-6), varicocele rats administered respectively with aqueous (500 mg/kg) and ethanolic (100 mg/kg) extracts of D. arborea. All rats (except normal and sham-operated groups) underwent varicocele induction. At the end of the treatment period, sexual organ weights, oxidative stress, sperm characteristics and some biochemical parameters were measured.Results:A significant decrease (p<0.01) in sperm density (137.81±7.76 vs. 175.83±4.86), sperm motility (55.43±4.49 vs. 77.96± 3.15) and sperm normality (44.75±2.80 vs. 79.25±1.84) was noticed in varicocele-untreated rats compared with controls. Varicocele also induced oxidative stress by decreasing superoxide dismutase (SOD) and catalase activities, and increasing malondialdehyde (MDA) levels. These alterations were prevented by D. arborea. For instance, the aqueous extract of D. arborea (500 mg/kg) significantly increased (p<0.05-0.001) testes and epididymis weights, sperm viability and sperm motility, while the ethanolic extract (100 mg/kg) increased sperm normality compared with varicocele-untreated rats. D. arborea extracts also decreased MDA levels, but elevated catalase activity.Conclusions:Dracaena arborea prevents the deleterious effects of varicocele and could be considered as an alternative treatment of this physiopathology.