Melatonin epigenetic potential on testicular functions and fertility profile in varicocele rat model is mediated by silent information regulator 1.

BACKGROUND AND PURPOSE: Varicocele is a leading cause of male infertility. Melatonin is a highly pleiotropic neurohormone. We aimed to characterize the melatonin epigenetic potential in varicocele and the involved molecular mechanisms. EXPERIMENTAL APPROACH: Fifty-two male albino rats were randomly divided into four groups (13 rats each): control (I), melatonin (II), varicocele (III) and melatonin treated varicocele (IV) groups. Left varicocele was induced by partial left renal vein ligation. Reproductive hormones, epididymal sperm functional parameters, testicular 3/17 ß-hydroxysteroid dehydrogenases, antioxidant enzymes, malondialdehyde, nicotinamide adenine dinucleotide phosphate oxidase, 8-hydroxy-2'-deoxyguanosine and histopathological/Johnsen's score were evaluated. Flow cytometry and Comet were carried out to explore extent of sperm and testicular DNA damage. Testicular expression of silent information regulator 1 (SIRT1), forkhead transcription factors-class O (type1) (FOXO1), tumour suppressor gene, P53, cation channels of sperm (CatSper) and steroidogenic acute regulatory protein was evaluated by western blot technique. Testicular expression of Bcl-2 and its associated X protein and nuclear factor kappa-light-chain-enhancer of activated B cells were assayed by immunohistochemical staining. Testicular miR-34a expression was quantified by quantitative reverse transcription-polymerase chain reaction. KEY RESULTS: The varicocele induced testicular histological injury, enhanced oxidative stress, P53-mediated apoptosis, DNA damage and increased testicular miR-34a expression paralleled with down-regulated SIRT1/FOXO axis. Melatonin treatment of varicocele rats displayed antioxidant/anti-apoptotic efficacy and improved reproductive hormones axis, CatSper expression and fertility parameters. MiR-34a/SIRT1/FOXO1 epigenetic axis integrates testicular melatonin mediated intracellular transduction cascades in varicocele. CONCLUSION AND IMPLICATIONS: Melatonin can be used as an adjuvant therapy to improve varicocele and its complication.

Verbascoside attenuates experimental varicocele-induced damage to testes and sperm levels through up-regulation of the hypothalamus-pituitary-gonadal (HPG) axis.

CONTEXT: Verbascoside (VB), which is found in many medicinal plant families, exhibits biological activities in various diseases. However, its effects on varicocele (VCL)-induced damage remain unknown. OBJECTIVE: To investigate the effects and mechanism of VB on experimental rats with varicocele (VCL)-induced damage. MATERIALS AND METHODS: Sixty sexually mature male Sprague-Dawley (SD) rats were divided into six groups (n = 10): control, control-sham, VCL-vehicle (normal saline), and VCL + VB groups (50, 100, and 200 mg/kg/day, intraperitoneally). After 4 weeks of VB treatment, all animals were sacrificed, and the body and testicular weight, sperm quality parameters, histopathology, antioxidant status, and hormone levels were tested. The levels of gonadotropin-releasing hormone (GnRH) and gonadotropin-inhibitory hormone in the hypothalamus were detected by western blot. RESULTS: Compared with the VCL-vehicle group (41.14%), administration of VB significantly increased the sperm viability (59.29, 65.45, 84.93%). VB groups showed higher Johnson's score (3.57 ± 0.15, 4.71 ± 0.26, 7.93 ± 0.37) than VCL-vehicle group (2.72 ± 0.24). Antioxidant status and hormone levels alterations were also observed. Meanwhile, the mean number of apoptotic tubules (8.15 ± 0.96, 6.61 ± 1.05, 2.17 ± 0.08) and apoptotic index showed a marked decrease. Compared with the VCL-vehicle group (0.21 ± 0.09), the VB groups (0.36 ± 0.07, 0.42 ± 0.06, 0.88 ± 0.10) showed considerable increases in GnRH. DISCUSSION AND CONCLUSIONS: VB has protective effects on reproductive organs and VB may be therapeutically useful in the treatment of varicocele through up-regulation of the HPG axis.

Body mass index and age correlate with antioxidant supplementation effects on sperm quality: Post hoc analyses from a double-blind placebo-controlled trial.

Spermatozoa are vulnerable to lack of energy and oxidative stress as a result of elevated levels of reactive oxygen species. Therefore, it is essential that appropriate nutrients are available during maturation. This randomised, double-blind, placebo-controlled trial investigated the effect of 6-month supplementation with carnitines and other micronutrients on sperm quality in 104 subjects with oligo- and/or astheno- and/or teratozoospermia with or without varicocele. Semen analyses were done at the beginning and end of the treatment. In addition to main analyses, post hoc analyses for age and body mass index (BMI) were carried out. Results were interpreted by dividing the population into two age and BMI classes. In 94 patients who completed the study, all sperm parameters increased in supplemented patients compared to the placebo group. A significant (p = .0272) difference in supplementation efficacy was observed for total motility on patients with varicocele and BMI < 25. In the same group, also the progressive motility was significantly superior (p = .0159). For Responder analysis, total motility results were confirmed in both the cited group (p = .0066) and in the varicocele group with BMI < 25 and age < 35 (p = .0078). This study suggests that supplementation is more effective in subjects with varicocele younger than 35 years with BMI < 25.

Hesperidin attenuated apoptotic-related genes in testicle of a male rat model of varicocoele.

BACKGROUND: Varicocoele is a swollen bulge of the pampiniform venous plexus inside the scrotum. It is also considered one of the causes of infertility in males. It has been demonstrated that hesperidin has remarkable pharmacological potentials, including antioxidant, anti-inflammatory, antimicrobial, and anticarcinogenic effects. OBJECTIVE: The present study aimed to evaluate the protective effect of hesperidin on varicocoele-induced testicular tissue damage and oxidative stress in the testicles of adult male rats. MATERIALS AND METHODS: Animals were assigned into the following groups: control group (Ctrl) or sham, varicocoele group (Vcl) which received no treatment, varicocoele group that was daily fed with hesperidin (Vcl+Hsp) at a dose of 50 mg/kg for eight weeks, and hesperidin group (Hsp) which received only hesperidin. At the end of the treatment period, the levels of oxidative stress markers were measured in plasma, and the expression of Bax and Bcl-2 was determined by immunocytochemistry and RT-qPCR methods. The index of apoptosis was assessed by the TUNEL assay. RESULTS: Johnsen's score, the epithelium thickness, and diameter of seminiferous tubules were improved in the Vcl+Hsp group as compared to the Vcl group. Treatment with hesperidin enhanced the serum levels of glutathione peroxidase (GPx) and superoxide dismutase (SOD) enzymes and decreased the heightened concentrations of malondialdehyde (MDA) in testicular tissue (p < 0.001). Moreover, our results demonstrated that hesperidin considerably diminished Bax and increased Bcl-2 expression (gene and protein) levels compared with the Vcl group (p < 0.05). It also markedly reduced the rate of programmed cell death in germ cells (p < 0.05). CONCLUSIONS: It seems that the treatment with hesperidin could mitigate testicular tissue damage in rats underwent varicocoele possibly through its antioxidant properties.

Long-term NaHS administration reduces oxidative stress and apoptosis in a rat model of left-side varicocele.

The main aim of this study was to assay the testicular H2 S levels in the varicocele rat model and then to investigate the protective effects of NaHS on morphometric changes, sperm parameters, oxidative stress and apoptosis markers in rat's testis. D,L-propargylglycine (PAG) was administrated to show the effects of cystathionine γ-lyase enzyme (CSE) inhibition in the varicocele. Rats were assigned to four groups: (a) Sham, (b) varicocele, (c) varicocele + PAG and (d) varicocele + NaHS. Animals in varicocele + NaHS group received 30 µmol/L NaHS in drinking water for 56 days. In the varicocele + PAG group, animals received PAG 19 mg/kg twice a week. Morphometric assessment, oxidative stress markers, testicular H2 S levels, sperm parameters, TUNEL assay and expression of Bax/Bcl2 were evaluated at the end of experiment. Testicular H2 S levels were significantly decreased in varicocele group. NaHS significantly improved sperm parameters, morphometric characteristics and oxidative stress compared to varicocele group. Oxidative stress status deteriorated in the PAG group compared to the varicocele group. This study showed that a low testicular H2 S level might play a critical role in male infertility. Thus, NaHS administration may be a promising treatment strategy for male infertility in varicocele. In addition, CSE may not be the only important enzyme in testicular H2 S production.

The ameliorative effect of monotropein, astragalin, and spiraeoside on oxidative stress, endoplasmic reticulum stress, and mitochondrial signaling pathway in varicocelized rats.

BACKGROUND: Monotropein, astragalin, and spiraeoside (MAS) are active compounds extracted from medicinal herbs; monotropein from Morinda officinalis How (Rubiaceae), astragalin (kaempferol 3-O-glucoside) from Cuscuta chinensis Lamark (Convolvulaceae) and spiraeoside from the outer scales of Allium cepa L. (Liliceae) in a ratio of 6.69:0.41:3.61. Monotropein, astragalin, and spiraeoside are well-known antioxidants, anti-inflammatory, and antinociceptive agents. The current investigation aims to study the molecular mechanism of varicocele-induced male infertility and the underlying pharmacological mechanisms of MAS. METHODS: Four groups were included: control (CTR), MAS 200 group (MAS 200 mg/kg), varicocele group (VC), and VC + MAS 200 group (MAS 200 mg/kg). Sprague-Dawley (SD) rats were treated with 200 mg/kg MAS or vehicle once daily for 28 days. The possible signaling mechanism and effects of MAS were measured via histological staining, immunohistochemistry, western blot, and biochemical assays. RESULTS: Parameters such as sperm motility and count, Johnsen's scores, spermatogenic cell density, serum testosterone, testicular superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and expression of the steroidogenic acute regulatory protein (StAR) improved significantly in the VC + MAS 200 group compared with the VC group. MAS treatment of varicocele-induced group significantly decreased the levels of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as testicular interleukin-6 (IL6), tumor necrosis factor-α (TNF-α), ROS/RNS, and malondialdehyde (MDA). It also decreased the apoptotic index and reduced the expression of endoplasmic reticulum (ER) protein levels (Grp78, p-IRE1α, and p-JNK) and apoptotic markers such as cleaved caspase-3 and Bax/Bcl2 ratio. CONCLUSION: This study suggests that the crosstalk between oxidative stress, ER stress, and mitochondrial pathway mediates varicocele-induced testicular germ cell apoptosis. MAS promotes spermatogenesis in varicocele-induced SD rat, probably by decreasing cytokines (IL-6, TNF-α) levels, regulating abnormal sex hormones, and decreasing oxidative stress, ER stress, and apoptosis.

Correlation of oxidation-reduction potential with hormones, semen parameters and testicular volume.

Seminal oxidative stress (OS) is a major cause of male factor infertility and can be measured as oxidation-reduction potential (ORP). Studies showed significant negative relationships of ORP with sperm count, motility or DNA integrity. Since these parameters are also positively or negatively associated with reproductive hormones follicle-stimulating hormone (FSH), luteinising hormone (LH), testosterone, testicular volume and the occurrence of varicocele, it is important to understand the mechanistic relationship between ORP and hormonal and/or testicular parameters. Therefore, we studied the relationship between ORP levels, standard hormone profiles and testicular volume in infertile men with and without varicocele. Results show a highly significant negative relationship of ORP with testicular volume and significantly positive correlations with FSH and LH. Yet, when adding varicocele as covariate, the relationship with FSH/LH became nonsignificant. Contrary, the presence of varicocele had only a contributing influence on the association of ORP with the testis volume. No association was found with estradiol. We propose that since OS causes degeneration of Sertoli cell with testicular shrinkage, such negative effect would result in a negative feedback on the hypothalamus with less inhibin secretion. This may result in increased secretion of LH and FSH. Thus, systemic and/or local OS may be responsible for smaller testis volumes.

[Intervention effect of Modified Dahuang Zhechong Granule on epididymal morphological changes in experimental varicocele rats].

OBJECTIVE: To explore the effect of Modified Dahuang Zhechong Granule (MDZG) on the development and maturation of epididymal sperm in experimental varicocele (VC) rats. METHODS: Sixty SD male rats were randomly divided into six groups of equal number, sham operation, VC model, Aescuven forte, and low-, medium- and high-dose MDZG. The model of left VC was made by the Turner method in all the rats except those of the sham operation group, followed by treatment with 0.9% normal saline for the animals in the sham operation and VC model groups, Aescuven forte tablets at 54 mg per kg of the body weight for those in the Aescuven forte group, and MDZG at 0.6, 1.2 and 2.4 g/ml for those in the low-, medium- and high-dose MDZG groups, all administered intragastrically qd for 8 successive weeks. Then, all the rats were sacrificed and their left epididymides harvested for examination of the quality of the epididymal sperm and the local microscopic and ultrastructural changes of the epididymal tissue. RESULTS: The VC model rats showed significant apoptosis of the epididymal sperm cells, interstitial edema, microvascular dilatation, degeneration and degeneration of the epithelial cells, degeneration of some principal cells and basal cell vacuoles, and immature spermatids in the lumen. Sperm motility was significantly increased in the Aescuven forte and low-, medium- and high-dose MDZG groups as compared with the VC models (P <0.01). Both sperm concentration and motility were markedly higher in the high-dose MDZG than in the Aescuven forte group (P <0.05). Remarkable apoptosis of epididymal sperm cells was observed in the microenvironment of sperm development in the VC models, which exhibited no statistically significant difference from that in the rats of the medium- and high-dose MDZG groups. CONCLUSIONS: Experimental varicocele induced local apoptosis of epididymal sperm cells, interstitial edema and microvascular dilatation in the rat epididymis, while Modified Dahuang Zhechong Granule could improve the stability of epididymal sperm maturation and contribute to their development.

Berberine reinforces Sertoli cells niche and accelerates spermatogonial stem cells renewal in experimentally-induced varicocele condition in rats.

BACKGROUND: Varicocele is present in 10-20% of the male infertile population. PURPOSE: Present study was done to demonstrate the reinforcing effect of berberine (BBR), as an antioxidant and anti-inflammatory agent, on Sertoli cells-related niche and spermatogonial stem cells (SSCs) self-renewal in experimentally-induced VCL condition. STUDY DESIGN: 50 mature male Wistar rats were divided into control, control-sham, non-treated VCL-induced, 50 mg kg-1 and 100 mg kg-1 BBR-treated VCL-induced groups. METHODS: The Leydig and Sertoli cells distribution and Leydig cells steroidogenic activity, expression of glial cell line-derived neurotrophic factor (GDNF), proto-oncogene Rearranged during Transfection (c-RET) receptor, Ets variant gene 5 (Etv5) and B-cell chronic lymphocytic leukemia (CLL)/lymphoma 6, member B (Bcl-6b) at mRNA and protein levels were analyzed. The mRNA integrity and DNA fragmentation were assessed. Finally, the serum levels of testosterone, inhibin B and testicular total antioxidant capacity, total thiol molecules, catalase, and malondialdehyde were evaluated. RESULTS: Observations revealed that, the BBR significantly enhanced VCL-reduced Leydig and Sertoli cells population, maintained Leydig-Sertoli cells network, enhanced GDNF, c-RET Etv5 and Bcl6b expression, up-regulated testicular antioxidant and endocrine status. CONCLUSION: The BBR by boosting Leydig-Sertoli cells network up-regulates the GDNF, Etv5 and Bcl-6b expression/synthesis in SSCs, which in turn improves SSCs self-renewal activities. Thus, the BBR could be considered as an appropriate agent for antioxidant therapy of VCLs. However, more studies with bigger sample number and focus on BBR-induced effects on other genes involving in the self-renewal process are needed to have more deterministic results.

Effect of selenium on testicular damage induced by varicocele in adult male Wistar rats.

PROJECT: Varicocele is an abnormal tortuosity and distension of the veins of the pampiniform plexus in the spermatic cord. It is the most common surgically correctable cause of male infertility. Several studies have revealed the effects of increased oxidative stress on serum, semen, and testicular tissues in patients with varicocele or in animal models. The aim of this study was to investigate the effects of sodium selenite on testicular damage induced by experimental left varicocele in male Wistar rats. PROCEDURE: In the present study, the effects of oral administration of sodium selenite (at doses of 0.05, 0.1, 0.2, and 0.4mg/kg bw) were assessed in normal and varicocelized rats. RESULTS: The varicocelized control rats showed decrease in sperm quality parameters, decreased activity of testes CAT, GPX and SOD, increased levels of MDA, and damage in testicular architecture. Administration of sodium selenite significantly reduced these changes to nearly normal levels, but did not change these parameters in normal rats. Histopathological studies further confirmed the protective effects of sodium selenite on varicocele-induced testicular damage in rats. Administrations of sodium selenite did not change these parameters in normal rats. CONCLUSIONS: Taken together, the results of this study suggest that sodium selenite treatment may have beneficial effect on the testes of varicocelized rats.

Evaluation of enzymatic and non-enzymatic antioxidants in seminal plasma of men with genitourinary infections, varicocele and idiopathic infertility.

UNLABELLED: This study was aimed to assess the antioxidant enzymatic and non-enzymatic compounds in semen of infertile men. Seventy-four infertile patients were grouped according to their clinical diagnosis: genitourinary infection, varicocele, idiopathic infertility. Semen samples of fertile men represent the control. Semen characteristics were evaluated by light and transmission electron microscopy (TEM). TEM data was quantified with a mathematical formula, which provides numerical scores. Spectrophotometric and HPLC methods were used to measure the amount of reduced (GSH), oxidised glutathione (GSSG), ascorbic acid (AA) and malondialdehyde (MDA, marker of lipid peroxidation) and the activity of glutathione reductase, catalase (CAT), glutathione peroxidase. Infertile groups showed significantly decreased values of sperm parameters vs. CONTROLS: In infection and varicocele groups, the seminal MDA levels were significantly increased when compared to controls (p < 0.001), indicating an alteration of oxidative status and a peroxidative damage. In infection and varicocele groups, AA levels were reduced (p < 0.05) vs. control; in the varicocele group, the GSH levels were also decreased (p < 0.05). Significantly higher CAT activity was observed in infection and varicocele groups vs. fertile men (p < 0.001 and p < 0.05 respectively). The GSH/GSSG ratio was significantly decreased in varicocele and idiopathic infertility groups vs. control (p < 0.01). The study of the alteration of a single parameter of oxidative stress or of the antioxidant system may not have a relevant clinical value to estimate male fertilising potential and the background of infertility causes, since complex and multifactorial mechanisms are involved in different pathologies. In our study, each pathology is characterised by a definite pattern of markers such as MDA and enzymatic and non-enzymatic antioxidant compounds. In the different pathologies related to infertility, the identification of the complex of involved parameters could be useful in the diagnosis, prognosis and in the choice of a possible treatment such as specific antioxidant supplements.

Association of decreased spermatozoa omega-3 fatty acid levels and increased oxidative DNA damage with varicocele in infertile men: a case control study.

Varicocele is commonly associated with male infertility because it impairs normal sperm morphology and activity. Polyunsaturated fatty acids (PUFA) are important determinants of sperm cell structure and function, but their relationship with varicocele remains unclear. The aim of the present study was to investigate the PUFA composition in spermatozoa of infertile men with varicocele and to evaluate the potential relationship between PUFA and varicocele. This case control study recruited 92 infertile men with varicocele, 99 infertile men without varicocele and 95 fertile male control subjects. Semen morphology and activity parameters were assessed and seminal plasma 8-hydroxy-2-deoxyguanosine (8-OHdG) content was determined by ELISA. Sperm concentrations of omega-3 and omega-6 fatty acids were measured by gas chromatography. Infertile men with varicocele had lower concentrations of omega-3 PUFA, higher omega-6:omega-3 PUFA ratios and greater oxidative DNA damage in spermatozoa compared with infertile men without varicocele and normal subjects. The degree of varicocele and DNA damage was associated with decreased omega-3 PUFA concentrations and semen quality in infertile men with varicocele. The findings suggest that omega-3 PUFA deficiency could be implicated in varicocele-associated infertility, and highlight the need for intervention trials to test the usefulness of omega-3 supplementation in reducing sperm abnormalities in infertile men with varicocele.

Expression and Subcellular Localization of Retinoic Acid Receptor-α (RARα) in Healthy and Varicocele Human Spermatozoa: Its Possible Regulatory Role in Capacitation and Survival.

Varicocele, an abnormal tortuosity and dilation of veins of the pampiniform plexus, is the most common identifiable and correctable cause of male infertility. It is now becoming apparent that signaling through vitamin A metabolites, such as all-trans retinoic acid (ATRA), is indispensable for spermatogenesis and disruption of retinoic acid receptor-α (RARα) function may result in male sterility and aberrant spermatogenesis. Herein, we investigated by Western blot and immunogold electron microscopy the expression profiles and subcellular localization of RARα in healthy and varicocele human sperm; in addition, we analyzed the effects of ATRA on cholesterol efflux and sperm survival utilizing enzymatic colorimetric CHOD-PAP method and Eosin Y technique, respectively. In varicocele samples, a strong reduction of RARα expression was observed. Immunogold labeling evidenced cellular location of RARα also confirming its reduced expression in "varicocele" samples. Sperm responsiveness to ATRA treatment was reduced in varicocele sperm. Our study showed that RARα is expressed in human sperm probably with a dual role in promoting both cholesterol efflux and survival. RARα might be involved in the pathogenesis of varicocele as its expression is reduced in pathologic samples. Thus, ATRA administration in procedures for artificial insemination or dietary vitamin A supplementation might represent a promising therapeutic approach for the management of male infertility.

Effects of anthocyanin extracted from black soybean seed coat on spermatogenesis in a rat varicocele-induced model.

Varicocele is the most common cause of primary male infertility and is associated with oxidative stress. The aim of the present study was to investigate the effects of anthocyanin on a rat model of varicocele. Twenty-four male rats were divided into four experimental groups: a normal control group, a varicocele-induced control group and two varicocele-induced groups treated with either 40 or 80mgkg(-1), p.o., anthocyanin for 4 weeks. Varicocele was induced by the partial obstruction of the left renal vein. After 8 weeks, the testes and epididymides from rats in all groups were removed, weighed and subjected to histological examination and semen analysis. Apoptosis in the testes was determined by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) and oxidative stress was assessed by measuring 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. Although no significant differences in sperm counts were observed among the groups, anthocyanin treatment of the varicocele-induced groups resulted in significantly increased testes weight, sperm motility and spermatogenic cell density (P<0.05). Anthocyanin treatment also significantly decreased apoptotic body count and 8-OHdG concentrations (P<0.05). We suggest that the antioxidant effect of anthocyanin prevented the damage caused by varicocele-induced reactive oxygen species.

The ameriorating effects of grapefruit seed extract on testicular morphology and function of varicocelized rats

Varicoceles are abnormal tortuosity and dilatation of the veins of the pampiniform plexus that drain the testis. The pathophysiology of testicular damage in varicocele has not been completely understood. However there is an increasing body of evidence pointing towards the role of reactive oxygen species and oxidative stress in the pathogenesis of varicocele related subfertility. In the present study we examined the role of proanthocynidin-rich ethanol extract of grapefruit seed as an antioxidant in protecting the testis against damage in experimental varicocele. Three groups of rats were constructed as the first group had intact rats; experimental bilateral varicoceles were established by complete ligation of the left and right main spermatic veins in the later two groups. The third group had in addition daily gavage administration of 1 Omg/ kg body weight ethanol extract of grapefruit seed. Eight weeks after varicocele induction, bilateral testicular weights, bilateral testicular volumes, bilateral caudal epididymal sperm characteristics, and bilateral testicular histology and serum hormone levels were tested. It was found that the testes of grapefruit seed extract treated animals had better functional and histological profiles compared to the untreated varicocelized animals. These results indicated the effectiveness of grapefruit seed extract for preservation of testes function morphology in varicocelized subjects.

Los varicoceles son tortuosidades anormales y dilataciones de las venas del plexo pampiniforme que drenan el testículo. La fisiopatología del daño testicular en el varicocele no se ha entendido completamente. Sin embargo, existe un creciente cúmulo de evidencias que apunta hacia el papel de especies reactivas al oxígeno y al estrés oxidativo, en la patogénesis del varicocele relacionados con subfertilidad. En el presente estudio, se examinó el papel de proantocianidina en el extracto etanólico de semilla del pomelo, como un antioxidante en la protección contra el daño testicular experimental en el varicocele. Tres grupos de ratas fueron seleccionados, un grupo de ratas control y dos grupos experimentales. En estos dos últimos grupos, se provocó varicocele bilateral a través de la ligadura completa de las venas testiculares principales izquierda y derecha. El tercer grupo tuvo además una sonda de administración diaria de 10 mg /kg de peso corporal, de extracto etanólico de semilla de pomelo. Ocho semanas después de la inducción de varicocele, se determinó el peso testicular bilateral, volúmenes testiculares bilaterales, características de los espermatozoides de la cola del epidídimo bilateral, la histología testicular bilateral y los niveles séricos de hormona. Se determinó que los testículos de los animales tratados con extracto de semilla de pomelo presentaban una mayor funcionalidad y mejores perfiles histológicos, en comparación con los animales varicocelizados no tratados. Estos resultados indican la eficacia de extracto de semilla de pomelo para la conservación de la morfología funcional testicular, en sujetos varicocelizados.

[Effect of soluble granule of Shengjing on the apoptosis in spermatogenic cells of rats caused by varicocele].

OBJECTIVE: To investigate the apoptosis of spermatogenic cells of rats caused by experimental varicocele and effect of soluble granules of Shengjing on the apoptosis. METHODS: Sixty Wistar male rats were divided into three group: control group, model group, and treatment group. Experimental varicocele was induced by partial ligation of the left renal vein in Wistar rat. Apoptosis cells in the testes were detected by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) Technique. RESULTS: The apoptosis index in model group was remarkably higher than that in control group (P < 0.001). There was significant difference between treatment and model groups in apoptosis index. CONCLUSION: The apoptosis of spermatogenic cells by varicocele may play a important role in leading to subfertility. The soluble granules of Shengjing have negative effects on the apoptosis of spermatogenic cells. The medicine can not only protect spermic production but improve the ability of procreation of testes.

[Bilateral microsurgical varicocelectomy in infertile men]. / Mikrokhirurgicheskaia dvukhstoronniaia varikotseléktomiia u muzhchin, stradaiushchikh besplodiem.

UNLABELLED: We assessed how bilateral microsurgical varicocelectomy alters semen quality in a large cohort of infertile men with bilateral varicocele. By means of bilateral testicular biopsy, we have investigated the spermatogenesis failure in several biological men groups and determined whether it can change the patient's candidacy for assisted reproductive technology procedures (ART). MATERIALS AND METHODS: From 1993 until 2003 in the urology and andrology department of St. Antoine hospital (1993-1994), the Tenon hospital (1994-2003) and hospital Saint Louis (1997-2003), 956 patients with varicocele were consulted and operated for primary or secondary sterility. Bilateral varicocele was observed in 219 patients. Our study included 198 patients with clinical palpable and infraclinical (ultrasonic doppler scanning) bilateral varicocele who underwent microsurgical bilateral varicicolectomy with bilateral testicular biopsy. Mean patient age was 34.5 (range 19 to 65) years. Varicocele has been classified into 4 stages. All the patients underwent a complete physical examination, including supine and standing scrotal examination, as well as testicular volume determination using a standard orchidometer. Complementary investigation included: the hormone status (FSH, LH, testosterone), semen analyses (carnitine, LDHx, fructoze, zinc). On the basis of the total motile sperm count 198 patients were divided into 5 biological groups: 10 azoospermia and oligospermia extreme (0-1) x 10(6)/cc--83 patients (41.9%); 2) oligospermia severe (1.1-5) x 10(6)/cc)--37 patients (18.7%); 3) oligospermia moderate (5.1-10) x 10(6)/cc)--36 patients (18.9%). To measure the sperm quality, the spermogram was studied 3, 6 and 12 months after the operation. On the basis of testicular biopsy we defined the following spermatogenesis groups: normal spermatogenesis--9 cases, hypospermatogenesis--141 cases, maturation arrest (early-6, late-20), Sertli cell only syndrome (SCOS)--17, tubular and peritubular sclerosis--5. The correlative analysis between the FSH classes and azoo- and oligospermic subsets (83 patients) shows that azoo-oligospermic area as a whole represents only 2 patients (2.4%) in the low FSH class, 46 (55.4%) in the normal FSH range class II, 39 (46.9%) patients in the high FSH class III. All the patients were divided into 4 groups according to the type of ART for which they qualified including 0 to 1.5 million/ml (intracytoplasmatic sperm injection-ICSI)--79 patients, 1.5 to 5 million/ml (in vitro fertilization-IVF)--33 patients, 5 to 20 million/ml (intrauterine insemination--IUI)--47 patients and 20 million/ml or greater sperm (spontaneous pregnancy candidates)--39 patients. RESULTS: Postoperative sperm concentration increased significantly compared to the one before the varicocelectomy. In the group of our patients the results were the following: of 198 patients 105 (53.1%) improved the spermogram, 44 (22.2%) worsened the spermogram, the spermogram was not changed in 49 (24.8%). In the first biological group of 83 patients, 42 (50.6%) improved the spermogram that enables using several methods for this difficult group (ICSI, IVF) for assisted reproductive technique (ART). The total amount of motile sperm per ejaculation increased from (0.09 +/- 0.030) x 10(6) before varicocelectomy up to (8.9 +/- 1.3) x 10(6) afterwards. In this group the testicular biopsy shows different variants of spermatogenesis disturbances, respectively. As for biological groups 3, 4 and 5, the observed spermogram improvements sharply increased the patients' liability to spontaneous pregnancy and make them intrauterine insemination candidates. CONCLUSIONS: Microscopic varicocelectomy has minimal morbidity and recurrence and may be beneficial for certain patients. Making simultaneous biopsy in patients with azoospermia and severe oligospermia makes it possible to distinctly define the extent of spermatogenesis disturbances and to elaborate adequate treatment policy. The drastic improvement of the sperm quality after varicocelectomy increases the ART chances for spontaneous pregnancy.

[Effects of hyperbaric oxygenation on rabbits 'testes with varicocele].

OBJECTIVE: To study the mechanism of male infertility caused by varicocele by evaluating the effects of hyperbaric oxygenation (HBO) therapy on the testicular tissue morphology and function of rabbit model with varicocele(VC). METHODS: Twenty-four mature male rabbits were randomly divided into three groups: pseudo-operation, VC model and VC model administered by HBO. Experimental varicocele was induced by partial ligation of the left "lumbotesticular" trunk vein in rabbits. HBO was administered to one of the two groups of VC model rabbits after the operation. Weight and volume of both testes, parameters of seminal fluid, histological changes of testicular tissues, MTDs, TFI, and Sertoli cell index (SI) of seminiferous tubules were studied. RESULTS: The average weight and volume of the left testes significantly increased in the rabbits treated by HBO. The semen quality was improved, and MTDs increased significantly compared with VC group(P < 0.0001). The testicular tissue morphology became nearly normal in VC + HBO group. CONCLUSIONS: 1. Both the structure and spermatogenetic function of testes can be damaged by the presence of varicocele; 2. Chronic ischemia, anoxia and microcircular dysfunction may be the key process and essential factor that make varicocele contributive to testicular damage and spermatogenetic dysfunction; 3. HBO can effectively alleviate, even eliminate, chronic ischemia, anoxia and microcircular dysfunction in testicular tissues with varicocele, and thus protect the structure and functions of testes.