Aerobic exercise blocks interleukin‐6 levels and germ cell apoptosis in obese rats

To investigate the effect of a high‐fat diet and aerobic exercise intervention and its related mechanism on rat germ cell apoptosis. Forty male Sprague‐Dawley rats were randomly divided into control group, high‐fat diet group, control exercise group and high‐fat exercise group. Rats were fed with high‐fat diet or were given weight‐free swimming. The levels of TG, TC, HDL, LDL and IL‐6 in serum of rats were measured. The body weight, body length and inguinal fat weight were measured to calculate the Lee's index and lipid/body weight ratio. The expression of IL‐6 mRNA in inguinal fat and IL‐6R,Bcl‐2 and Bax mRNA in testis was detected by RT‐PCR. The morphological structure of testis was observed, and the Johnsen's ten‐point score was calculated by HE staining, and the germ cell apoptosis was detected by TUNEL method. We got from the experimental results: a high‐fat diet induces obesity and lipid metabolism disorder, alters testis morphological structure and increases germ cell apoptosis in rats. Aerobic exercise improves the lipid metabolism disorder and interferes with germ cell apoptosis by reducing interleukin‐6 and interleukin‐6 receptor expression.     

Carnosine prevents testicular oxidative stress and advanced glycation end product formation in D‐galactose‐induced aged rats

D‐Galactose is shown to mimic natural ageing in rodents by exacerbating oxidative stress and glycation. Steroid production and having a poor antioxidant system make testis vulnerable to galactose‐induced ageing. Antioxidation and antiglycating actions of carnosine may be intriguing for prevention of testicular ageing. In this study, male Wistar rats were applied D‐galactose (300 mg/kg; subcutaneously 5 days a week) and carnosine (250 mg/kg; intraperitoneally 5 days a week) along with D‐galactose for 2 months. D‐Galactose treatment increased testicular reactive oxygen species, thiobarbituric acid reactive substances, diene conjugates, protein carbonyls, advanced oxidation products of proteins and advanced glycation end products. Carnosine was capable of repelling oxidative stress and glycation produced by D‐galactose. Johnsen's score, which describes histopathological evaluation, was also significantly improved with preserved spermatogenesis by carnosine. It appears that carnosine deters the testicular oxidative stress due to galactose‐induced ageing directly by its antioxidative and antiglycating properties.     

Serum inhibin pro alphaC in infertile men.

Specific assays have been developed for bioactive inhibin dimers, inhibin A and B, and inhibin alpha-subunit precursor pro alphaC. To better understand the role of serum inhibin pro alphaC in infertile men, the authors measured these forms of inhibin in sera from 39 infertile men and analyzed inhibin relationships with serum gonadotropins, testosterone, and estradiol. All subjects had oligozoospermia. Inhibin A levels were undetectable in all subjects. Inhibin B concentrations were 117 +/- 59 pg/mL. Inhibit B concentrations correlated negatively with serum FSH (r = .584, p < .0001) and positively with sperm count (p < .01) and bilateral testicular volume (r = .607, p < .0001). The concentration of pro alphaC was 556 +/- 236 pg/mL (normal range, 446 +/- 28). Inhibin pro alphaC showed no correlation with serum FSH, LH, testosterone, sperm concentration, and bilateral testicular volume. In addition, inhibin pro alphaC was not correlated with inhibin B. Pro alphaC is unlikely to be a useful marker for spermatogenesis in infertile men compared with inhibin B.     

Protective effects of sea cucumber (Holothuria atra) extract on testicular dysfunction induced by immune suppressant drugs in Wistar rats

The current study was aimed to evaluate the protective effect of Holothurian atra (HA) extract; naturally occurring marine resource, against methotrexate (MTX) induced testicular dysfunction. Mature rats received either MTX (20 mg/kg, intraperitoneally) or saline on the 7th day of experiment al design. Seven days prior and after MTX‐injection, rats received HA at dose of 300 mg/kg intragastrically (HA + MTX group; HA group alone). Serum was extracted and testicular tissues were examined for the changes in serum biochemistry (liver & kidney biomarkers, testicular hormones and antioxidants), molecular and histopthological alterations using RT‐PCR and immunohistochemistry. MTX‐injected rats induced alteration in all testicular parameters. Prior administration of HA ameliorated the MTX‐induced oxidative stress. HA administration normalised MTX‐induced decrease in serum levels of interleukin‐6 (IL‐6), tumour necrosis factor alpha (TNF‐α), interferon‐gamma (IFN‐γ), reproductive hormones (FSH, LH and testosterone) and antioxidants GST, SOD and catalase. MTX‐injected rats down‐regulated mRNA expression of GST, SOD, steroidogenesis associated genes, IFN‐γ, Bcl2 and NFKB. MTX up‐regulated BAX expression and caspase 9 immunoreactivity that were ameliorated in HA + MTX group. Collectively, HA ameliorated and restored all altered genes. In conclusion, HA is a promising supplement that is helpful in protection against testicular cytotoxicity and dysfunction induced by methotrexate.     

Testicular follicle-stimulating hormone receptors in idiopathic male infertility

To ascertain whether abnormalities in testicular binding of follicle-stimulating hormone (FSH) are related with spermatogenic impairment found in idiopathic male infertility, we measured FSH receptors in testicular tissues obtained by biopsy from 48 infertile men. The 48 infertile men were divided into 3 groups by histological grading using Johnsen's score count, and testicular FSH receptors among these groups were compared. Although 9 of the 18 infertile men with low Johnsen's score count and 5 of the 15 men with middle score count had no obvious FSH binding sites with high affinity, all 15 men with a high score count had high affinity FSH binding sites. In connection with high affinity binding sites for FSH, maximum binding number (Bmax) decreased significantly with the degree of spermatogenic impairment, but the association constant (Ka) was similar among the 3 groups. The present findings demonstrate that the decrease in testicular high affinity binding sites for FSH is related with the degree of spermatogenic impairment found in idiopathic male infertility.     

Pituitary-gonadal feedback in testicular disorders

Stimulation response of the pituitary to LHRH and testicular biopsy were investigated in 17 infertile men in comparison to 10 healthy controls. A significant elevation of basal FSH and LHRH-stimulated FSH serum levels was observed in Sertoli cell only syndrome and spermatogenetic arrest, while LH and testosterone remained normal. The LHRH test seems to be of value for differentiation of pretesticular, testicular and posttesticular infertility.     

Downregulation of caspase‐9 is a frequent event in patients with stage II colorectal cancer and correlates with poor clinical outcome

Objective To evaluate the clinical significance of caspase‐9 mRNA expression and investigate its prognostic value in stage II colorectal cancer. Method Quantitative real‐time RT–PCR was used to analyse caspase‐9 mRNA expression in cancer tissue and corresponding normal mucosa from 120 patients. Results Compared with normal mucosa, the expression of caspase‐9 mRNA was found to be downregulated in cancer tissue (P = 0.001). Poorly differentiated cancer showed lower mRNA expression than cancer with greater differentiation (P = 0.031). The Kaplan–Meier survival analysis demonstrated that patients with downregulated caspase‐9 showed a worse overall survival (P = 0.012) and disease‐free survival (P = 0.022). Cox’s proportional hazards regression model confirmed that expression of caspase‐9 was the strongest prognostic factor in stage II colorectal cancer. Conclusion The mRNA expression of caspase‐9 can be used as an independent prognostic factor for patients with stage II colorectal cancer.     

The ameliorative effects of Ginkgo biloba on apoptosis,LH‐R expression and sperm morphology anomaly in testicular torsion and detorsion

Torsion/detorsion (T/D) induces testicular damages in both germinal epithelial and interstitial tissues. Ginkgo biloba extract (GbE) exerts antioxidant and free radical scavenger. We investigated the effect of GbE on testicular tissues, Leydig and sperm cells in rats injured with T/D. Twenty‐eight Wistar albino rats were randomly assigned into four groups (Control, GbE, Treatment: T/D+GbE, T/D). T/D performed to the rats in torsion, treatment received GbE (50 mg/kg) 1 hr before T/D, GbE group received only GbE (50 mg/kg) and control was defined as sham group. After T/D, the testes along with epididymis were removed and processed. LH‐R expression, apoptosis, sperm morphology and histopathological damage scores were determined for each group. Testicular T/D caused significant increases in apoptosis and sperm morphology anomaly, and a significant decrease in Johnsen's testicular biopsy scores, LH‐R expression of Leydig cell and normal sperm cell count. GbE ameliorated testicular histopathology and caused significant increases in LH‐R expression, normal sperm cell count in the treated and particularly GbE group. Consequently, GbE may prevent testicular injury and enhance Leydig and sperm cell activity following both T/D and normal situation owing to its antioxidant, anti‐apoptotic, free radical scavenger and anti‐inflammatory effects.     

Histopathological and biochemical comparisons of the protective effects of amifostine and l‐carnitine against radiation‐induced acute testicular toxicity in rats

The aim of this study was to compare the radioprotective efficacies of amifostine (AMI) and l ‐carnitine (LC) against radiation‐induced acute testicular damage. Thirty Wistar albino rats were randomly assigned to four groups: control (n = 6), AMI plus radiotherapy (RT) (n = 8), LC plus RT (n = 8) and RT group (n = 8). The rats were irradiated with a single dose of 20 Gy to the scrotal field. LC (300 mg/kg) and AMI (200 mg/kg) were given intraperitoneally 30 min before irradiation. The mean seminiferous tubule diameters (MSTDs) were calculated. Testicular damage was evaluated histopathologically using Johnsen's mean testicular biopsy score criteria. Malondialdehyde (MDA) and glutathione levels were measured in tissue samples. AMI plus RT and LC plus RT groups had significantly higher MSTDs than those in the RT group (p = .003 and p = .032 respectively). MDA values of both AMI plus RT and LC plus RT groups were significantly lower than those in RT group (p < .004 and p < .012 respectively). As a result, AMI and LC have a similar radioprotective effect against radiation‐induced acute testicular damage, histopathologically and biochemically.     

Analysis of histological findings of testicular biopsies in male infertility

Histological findings of testicular biopsy were studied following the Johnsen's score count method in 68 cases of idiopathic male infertility, and the relation between serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone (T) and histological findings were analyzed in the same cases. In oligozoospermia, there were no cases showing a Johnsen's score lower than 4. The score counts ranged widely from 1 to 9 in azoospermia. The cases with the Johnsen's score count lower than 4 revealed high values of serum LH and FSH and a low level of serum T. There was no relationship between Leydig cell accumulations or thickness of the seminiferous tubular walls and score values. Further examination using ABC (avidin biotin complex) method was carried out to find the localization of FSH and T in the testicular tissues. Immunohistochemical localization FSH was not noted in normal testicular tissues obtained the autopsy cases and testicular biopsy specimens of idiopathic male infertility. The localization of T was found in the Leydig cells and the Sertoli cells of normal and infertile testes. In the cases with the thickness of tubular walls, Sertoli cells were not stained. This fact might indicate that absence of T in Sertoli cells is related to spermatogenetic maturation only with the thickness of seminiferous tubular walls.     

Therapeutic effects of date palm (Phoenix dactylifera L.) pollen extract on cadmium‐induced testicular toxicity

Cadmium (Cd) is a well‐known testicular toxicant. This study was designed to explore the long‐term effects of a single low dose of Cd on spermatogenesis, and testicular dysfunction and oxidative stress, and the therapeutic potential of date palm pollen extract (DPP) in averting such reproductive damage. Adult male Wistar rats received a single intraperitoneal injection of CdCl₂ (0 or 1 mg kg^?1). Twenty‐four hours later, they started receiving DPP (0 or 40 mg kg^?1) orally, once daily for 56 consecutive days. Cd exposure caused significant reproductive damage via reduced weight of the reproductive organs, which includes spermatological damage (decreased sperm count and motility and increased rates of sperm abnormalities), increased oxidative stress (increased malondialdehyde and decreased reduced glutathione levels), histological alterations (necrosis, inefficient to completely arrest spermatogenesis and a reduced Johnsen's score) and decreased serum testosterone level. DPP restored spermatogenesis and attenuated the toxic effects of Cd on the reproductive system to the levels observed in the control animals. These findings support the hypothesis that the testis is particularly sensitive to Cd, which can cause testicular damage and infertility. Treatment with DPP can ameliorate the deleterious effects of Cd, probably by activating testicular endocrine and antioxidant systems.     

Effect of psychological stress on fertility hormones and seminal quality in male partners of infertile couples

The present study evaluated the effect of psychological stress on male fertility hormones and seminal quality in male partner of infertile couples. Seventy male partners of infertile couples were evaluated for level of psychological stress using Hospital Anxiety and Depression Score (HADS) questionnaire, serum total testosterone, luteinising hormone (LH) and follicle‐stimulating hormone (FSH) by electrochemiluminescence assay and serum GnRH by ELISA. Seminal analysis was performed as per WHO guideline. Nineteen (27%) of them had HADS anxiety and depression score ≥8 (abnormal HADS score). The persons having abnormal HADS had lower serum total testosterone, higher serum FSH and LH than those of persons having normal HADS. Serum total testosterone correlated negatively with HADS, but LH and FSH correlated positively. There was no change in GnRH with the change in stress or testosterone levels. Sperm count, motility and morphologically normal spermatozoa were lower in persons having abnormal HADS. Sperm count correlated positively with total testosterone and negatively with FSH and LH. Abnormal sperm motility and morphology were related to lower testosterone and higher LH and FSH levels. Psychological stress primarily lowers serum total testosterone level with secondary rise in serum LH and FSH levels altering seminal quality. Stress management is warranted for male infertility cases.     

Vitamin E administration does not ameliorate tramadol-associated impairment of testicular function in Wistar rats

Tramadol is widely abused in Nigeria and has been reported to cause fertility decline via testicular oxidative stress. This study investigated the effect of vitamin E, an antioxidant on some reproductive parameters in male Wistar rats administered tramadol. Twenty male Wistar rats (180–200 g) were randomly assigned into four groups (n = 5) thus: Control (0.2 ml vehicle: olive oil), tramadol-treated (20 mg/kg of tramadol), vitamin E-treated (100 mg/kg of vitamin E) and tramadol + vitamin E-treated (received tramadol and vitamin E) groups. Drugs were administered orally and daily for 28 days. Sperm count, Johnsen's score, germinal epithelial height and serum testosterone, follicle-stimulating hormone (FSH) and luteinising hormone (LH) concentrations were significantly (p < .05) decreased in tramadol-treated and tramadol + vitamin E compared with control and vitamin E-treated groups. Sperm motility, morphology, viability, seminiferous tubular diameter, Leydig cell count, Sertoli cell count and malondialdehyde, superoxide dismutase, glutathione peroxidase and catalase concentrations were not significantly different among the groups. Histology of testis and epididymis in all groups showed no toxicity but decreased sperm population in tramadol-treated and tramadol + vitamin E-treated groups. Tramadol did not cause testicular oxidative stress but impaired testicular function by suppressing testosterone, FSH and LH secretion. Vitamin E administration could not attenuate this impairment in testicular function.     

Testicular follicle-stimulating hormone receptors and effectiveness of human menopausal gonadotropin-human chorionic gonadotropin treatment in idiopathic male infertility

To investigate the relationship between testicular follicle stimulating hormone (FSH) receptors and the effectiveness of human menopausal gonadotropin (hMG-hCG) treatment in idiopathic male infertility, 48 infertile men were examined. Most of the 14 patients without detectable testicular high affinity FSH receptors did not show any increase in sperm count after the hMG-hCG treatment, whereas 23 of the 34 patients with FSH receptors responded to the treatment. In patients with FSH receptors, patients with a middle or high Johnsen's score count responded more than those with a low score count did. From the above results, it seems that both the presence or absence of testicular FSH receptors and the histological appearance of spermatogenesis predict responsiveness to hMG-hCG treatment in infertile men.     

Comparison of the protective effect of dipyridamole and acetylsalicylic acid on long-term histologic damage in a rat model of testicular ischemia-reperfusion injury

PurposeIschemia reperfusion injury arising from testicular torsion results in a loss of spermatogenesis and a significant increase in germ cell apoptosis. We investigated the effects of dipyridamole and acetylsalicylic acid (ASA), 2 well-known platelet inhibitors, on testicular ischemia reperfusion injury.MethodsThirty adult male Sprague-Dawley rats were randomly divided into 5 groups (n = 6 for each group): control, sham-operated, torsion/detorsion (T/D), T/D + dipyridamole, and T/D + ASA. Testicular ischemia was achieved by rotating the left testis 720° clockwise for 2 hours. Thirty minutes before torsion, 10 mg/kg dipyridamole was injected transperitoneally in the T/D + dipyridamole group, and 100 mg/kg ASA was injected transperitoneally in the T/D + ASA group. Sixty days after the initial surgical procedure, ipsilateral orchiectomies were performed for histopathologic examination to determine Johnsen's mean testicular biopsy score (MTBS), mean seminiferous tubular diameter (MSTD), and apoptotic index (AI) in all groups.ResultsUnilateral testicular torsion-detorsion led to a significant decrease in Johnsen's MTBS and MSTD values in the ipsilateral testis and a significant increase in AI values of the T/D group. There were no significant differences between the T/D + dipyridamole and control groups in terms of MSTD and MTBS values. Although an amount of improvement exits in T/D + ASA group, there were significant differences between the T/D + ASA and control group MSTD and MTBS values. There was no significant difference between the T/D + dipyridamole and control groups in terms of AI values (P > .05), but the differences between the T/D + ASA and control groups were significant despite a slight decline in AI values of the T/D + ASA group.ConclusionsOur findings show that the use of dipyridamole before testicular reperfusion has a potentially protective effect against long-term injury in testicular ischemia reperfusion injury.     

Probability to retrieve testicular spermatozoa in azoospermic patients

Aim: The degree of probability to retrieve spermatozoa from testicular tissue for intracytoplasmic sperm injection intooocytes is of interest for counselling of infertility patients. We investigated the relation of sperm retrieval to clinical dataand histological pattern in testicular biopsies from azoospermic patients. Methods: In 264 testicular biopsies from142 azoospermic patients, the testicular tissue was shredded to separate the spermatozoa, histological semi-thin sec-tions of which were then evaluated using Johnsen score. Results: The retrieval of spermatozoa correlated signifi-cantly (P < 0.001) with the testicular volume (r = 0.49), the FSH concentration ( r = -0.66), the maximum score(r = 0.85) and the mean Johnsen score (r = 0.81). In the multivariate regression analysis the successful testicularsperm extraction showed the closest relationship to the maximum score. The testicular volume correlated significantlywith the mean Johnsen score ( r = 0.64, P < 0. 001), and the basal serum FSH concen