The Effect of Schisandra chinensis Baillon on Cross-Talk between Oxidative Stress, Endoplasmic Reticulum Stress, and Mitochondrial Signaling Pathway in Testes of Varicocele-Induced SD Rat.

Schisandra chinensis Baillon (SC) has been utilized for its antioxidants and anti-inflammatory activities in a broad variety of medical applications. However; SC uses for improving fertility in males and related disorders with proper scientific validation remain obscure. The present study aimed to investigate the effects of SC on varicocele (VC)-induced testicular dysfunction and the potential molecular mechanism associated with VC-induced germ cell apoptosis. The male Sprague-Dawley rats were equally divided into four groups consisting of 10 rats in a normal control group (CTR), a control group administered SC 200 mg/kg (SC 200), a varicocele-induced control group (VC), and a varicocele-induced group administered SC 200 mg/kg (VC + SC 200). Rats were administrated 200 mg/kg SC once daily for 28 days after induction of varicocele rats and sham controls. At the end of the treatment period, body and reproductive organ weight, sperm parameters, histopathological damages, proinflammatory cytokines, apoptosis markers, biomarkers of oxidative stress, endoplasmic reticulum (ER) stress, and steroidogenic acute regulatory protein (StAR) were evaluated. The effects of SC extract on human sperm motility were also analyzed. SC treatment reduces VC-induced testicular dysfunction by significantly increasing testicular weight, sperm count and sperm motility, serum testosterone level, Johnsen score, spermatogenic cell density, testicular superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase level, and steroidogenic acute regulatory protein (StAR) level. Furthermore, the effects of SC on malondialdehyde (MDA) level, reactive oxygen species (ROS)/reactive nitrogen species (RNS) level, apoptotic index, serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, Glucose-regulated protein-78 (Grp 78), phosphorylated c-Jun-N-terminal kinase (p-JNK), phosphorylated inositol-requiring transmembrane kinase/endoribonuclease 1α (p-IRE1α), cleaved caspase 3, and Bax:Bcl2 in VC-induced rats were significantly decreased. Treatment with SC extracts also increased sperm motility in human sperm. Our findings suggest that the SC ameliorate testicular dysfunction in VC-induced rats via crosstalk between oxidative stress, ER stress, and mitochondrial-mediated testicular germ cell apoptosis signaling pathways. SC promotes spermatogenesis by upregulating abnormal sex hormones and decreasing proinflammatory cytokines (interleukin-6; TNF-α).

Improvements in Scrotal Thermoregulation in Patients with Varicoceles Treated by Using Traditional Korean Medicine: Two Case Reports.

A varicocele is a dilatation of the pampiniform venous plexus within the spermatic cord. The incidence of varicoceles is 15%, and it occurs in more than 40% of men in infertile couples. Traditional Korean medicine (TKM) has been used to treat male infertility in Korea. We present two cases of men with varicoceles diagnosed via physical examination and scrotal thermography. We treated these men for two months by using TKM techniques, which included acupuncture, pharmacopuncture, and herbal medicine. We used scrotal thermography to evaluate the varicoceles before and after TKM treatment. After TKM treatment, the scrotal thermoregulation of both patients improved. In Patient 1, the temperature difference between the left and the right pampiniform plexus (i.e., ΔTP) was 2.8°C before treatment. It decreased to 1.3°C after treatment. In addition, the temperature difference between the testicles (ΔTT) was 1.5°C before treatment; it decreased to 0.2°C after treatment. In Patient 2, the ΔTP was 1.5°C before treatment; it decreased to 0.2°C after treatment. This report is the first to show that TKM may be an option for treating patients with varicoceles, as determined by using a scrotal thermography evaluation.

Randomised clinical trial of comparing effects of acupuncture and varicocelectomy on sperm parameters in infertile varicocele patients.

The aim of the study was to evaluate the effect of the acupuncture treatment on sperm parameters and pregnancy rates in patients with primary infertility. Between January 2008 and May 2010, 30 men with the primary infertility (one year of unprotected intercourse, healthy wife) and varicocele with normal hormone levels and abnormal semen analysis were randomised into two groups. Group 1 underwent subinguinal microscopic varicocelectomy, and Group 2 underwent acupuncture treatment twice a week for 2 months. Both groups were evaluated with semen analysis at 6 months after the treatment. Patients in both groups evaluated with telephone calls and e-mail in terms of pregnancy. The mean age of the patients was 27.2, and groups were comparable regarding the age (P = 0.542). The pre-treatment sperm concentration, motility and morphological characteristics were similar in both groups. Sperm concentration and motility improved significantly in both groups after the treatment. Increase in sperm concentration was higher in the acupuncture group compared to the varicocelectomy group (P = 0.039). The average follow-up was 42 months, and pregnancy rates were emphasised 33% in both groups. Acupuncture treatment in primary infertile varicocele patients with semen abnormalities seems to be effective and has comparable results with the varicocelectomy treatment.

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.

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.

[Comparative assessment of extraperitoneoscopic and laparoscopic methods of varicocele treatment].

The article presents a comparative analysis of the results of extraperitoneoscopic and laparoscopic methods of internal seminal vein ligation in 90 varicocele patients (40 and 50 patients, respectively); describes insufficiently known method--extraperitoneoscopic operations. The working space in the prevesical space is created by direct introduction of trocars with optics into the prevesical space without any additional tools. The operations took the same time. Laparoscopic operations required more postoperative analgetic drugs than extraperitoneoscopic ones. By pain intensity and physical activity scales, varicocele patients' quality of life was higher after extraperitoneoscopic operations than after laparoscopic and open operations. Thus, extraperitoneal ligation of the seminal veins by direct introduction of endoscope into the preperitoneal space with CO2 insufflation without prior creation of working space is simple for use, low invasive, has low risk of visceral injury and can be applied as an alternative to laparoscopy.

[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.

The role of impairment of adrenal mineraloglucocorticoid function in the development of infertility in varicocele patients.

The study was aimed at the understanding of pathophysiological mechanisms of the impairment of spermatogenesis in varicocele patients. The crucial role of tension increase in the venous plexus of the spermatic cord in spermatogenesis damage in the testis on the varicocele side and absence of any effect of haemodynamic abnormalities on spermatogenesis in the complementary testis has been determined. Retrograde blood flow through the central vein of the left adrenal gland in varicocele has been evidenced by X-ray examination. The role of this phenomenon in the changes of functional activity of the adrenal gland is discussed. Results of the study of functional status of adrenal glands revealed their tendency to provide hyperactivity in synthesis of mineraloglucocorticoids. Correlation between cortisol level in peripheral blood and percentage of abnormal sperm in ejaculate was shown. This fact supported the idea about the existence of a causal interrelationship between abnormalities in the functional status of adrenal glands and development of infertility in varicocele patients.