Decreased Serum Testosterone Levels Research Articles

Protective effect of green tea extract against cadmium-induced testicular damage in rats in respect of oxidant/antioxidant equilibrium and androgen production

Objective: Investigating the effect of green tea extract (GTE) on the testicular damage induced by cadmium chloride CdCl2 in male rats. Design: Randomized controlled study. Animals: 40 male Wistar rats. Procedures: Rats were randomly divided into four groups: A) control group (each rat daily received pellet diet); B) GTE group each rat daily received pellet diet as well as 3 ml of 1.5 % w/v GTE, C) CdCl2 group each rat was I/P injected a single dose of 1 mg/kg CdCl2, then daily received pellet diet, and D) CdCl2+GTE group each rat was I/P injected a single dose of 1 mg/kg CdCl2 then daily received pellet diet as well as 3 ml of 1.5 % w/v GTE. After 30 days, blood samples were collected for hormonal assays (testosterone, FSH, and LH). In addition, both testes were collected; one of them was used for quantification of 17-beta hydroxysteroid dehydrogenase III (17β-HSDIII) gene expression using a real-time PCR. The other testis was used for determination of catalase and reduced glutathione; GSH, Nitric oxide (NO) and malondialdehyde (MDA) levels. Results: CdCl2 decreased serum testosterone levels and its synthesis pathway (17β-HSDIII testicular gene expression). While antioxidants catalase and GSH were reduced, oxidants MDA were enriched in the testes of CdCl2-poisoned rats. This CdCl2-promoted testicular dysfunction was corrected via the administration of GTE to male rats. Conclusion and clinical relevance: GTE could be used as a remedy for protecting against CdCl2-induced testicular damage in male rats.

Effects of gestational Perfluorooctane Sulfonate exposure on the developments of fetal and adult Leydig cells in F1 males

Studies have showed that some of the most common male reproductive disorders present in adult life might have a fetal origin. Perfluorooctane sulfonic (PFOS) is one of the major environmental pollutants that may affect the development of male reproductive system if exposed during fetal or pubertal periods. However, whether PFOS exposure during fetal period affects testicular functions in the adult is still unclear. Herein, we investigated the effects of a brief gestational exposure to PFOS on the development of adult Leydig- and Sertoli-cells in the male offspring. Eighteen pregnant Sprague-Dawley rats were randomly divided into three groups and each received 0, 1 or 5 mg/kg/day PFOS from gestational day 5–20. The testicular functions of F1 males were evaluated on day 1, 35 and 90 after birth. PFOS treatment significantly decreased serum testosterone levels of animals by all three ages examined. The expression level of multiple mRNAs and proteins of Leydig (Scarb1, Cyp11a1, Cyp17a1 and Hsd17b3) and Sertoli (Dhh and Sox9) cells were also down-regulated by day 1 and 90. PFOS exposure might also inhibit Leydig cell proliferation since the number of PCNA-positive Leydig cells were significantly reduced by postnatal day 35. Accompanied by changes in Leydig cell proliferation and differentiation, PFOS also significantly reduced phosphorylation of glycogen synthase kinase-3β while increased phosphorylation of β-catenin. In conclusion, gestational PFOS exposure may have significant long-term effects on adult testicular functions of the F1 offspring. Changes in Wnt signaling may play a role in the process.

Decrease in serum testosterone levels after short-term occupational exposure to diisononyl phthalate in male workers

ObjectiveThe objective of the study was to examine the effects of occupational exposure to diisononyl phthalate (DINP) on serum testosterone levels in male workers.MethodsFrom 2015 to 2018, 97 male workers...

Clinical and Metabolic Responses to Magnesium Supplementation in Women with Polycystic Ovary Syndrome.

We hypothesized that magnesium supplementation might help improve metabolic profiles and clinical symptoms of polycystic ovary syndrome (PCOS) through its role in insulin action. The present study aimed to investigate the effect of magnesium supplementation on metabolic profiles and levels of sex hormones in women with PCOS. In this parallel randomized, double-blind, placebo-controlled clinical trial, 60 women with PCOS aged 20-45years were recruited. After stratification for body mass index (BMI), age, and types of medications, participants were randomly assigned to consume magnesium supplements (containing 250mg magnesium oxide) or placebo for 8weeks. To assess biochemical indicators, a venous blood sample was taken after an overnight fasting. The mean age of study participants was 26.4years. We found that magnesium supplementation for 8weeks among women with PCOS had favorable effects on BMI compared with the placebo group (changes from baseline in intervention group: - 0.31 ± 0.07 vs. 0.07 ± 0.09kg/m2 in control group). In addition, the supplementation lead to preventing the increase in waist circumference in intervention group compared with the control group (0.02 vs. 1.15cm). No significant effects on glycemic variables and lipid profile were seen following the magnesium supplementation. A significant increase in serum LH levels in intervention group and a decrease in placebo group were observed (P = 0.01). Although we found a significant decrease in serum testosterone levels in intervention and placebo groups, comparing the changes between the two groups, a marginally significant difference in serum testosterone levels was found (51.65 vs. 47.80 in intervention, 43.41 vs. 39.46 in placebo, P = 0.08). A significant increase in serum dehydroepiandrogens (DHEA) (136.32 vs. 172.37 intervention, 102.74 vs. 120.15 placebo, P = 0.01) was seen in two groups. Magnesium supplementation had no significant effects on FSH, 17OH-progesteron, sex hormone-binding globulin (SHBG), and free androgen index (FAI) levels. We found evidence indicating that magnesium supplementation did not influence serum lipid profiles and glycemic indicators among women with PCOS. Magnesium supplementation resulted in reduced BMI and testosterone levels as well as increased DHEA concentrations in women with PCOS. Also, magnesium supplementation may increase serum LH levels. ClinicalTrials.gov IRCT registration no. NCT02178150.

Cisplatin induced testicular damage through mitochondria mediated apoptosis, inflammation and oxidative stress in rats: impact of resveratrol.

The target of this study was to explore the role of mitochondria mediated apoptosis and inflammation in cisplatin-induced testicular damage and to evaluate the ameliorative effect of resveratrol. Adult male Wistar rats were randomly allocated to 4 groups. Group I (Control) received normal saline, Group II (Resveratrol) received resveratrol (50 mg/kg/day), Group III (Cisplatin) received cisplatin (7.5 mg/kg/week, i.p.) and Group IV (Resveratrol + Cisplatin) received resveratrol and cisplatin in the same regimen of treatment. Treatment with resveratrol in Groups II and IV started 48h before cisplatin injection and continued for further 4 successive weeks. Cisplatin-treated rats showed reduced body weight, absolute testes weight and sperm count, motility and viability. On the other hand, cisplatin treatment increased the percentage of sperm abnormalities. It also decreased serum testosterone level, mitochondrial membrane potential while, increased cytochrome C liberation from the mitochondria into the cytosol. The activities of caspase-3 & -9 were increased. The level of TNF-α, IL-6 and Bax were increased whereas Bcl-2 was decreased. Oxidative stress markers were found to increase with a concomitant reduction in the antioxidant enzymes and GSH levels. These results were confirmed by immunohistochemical and histopathological analysis. Contrary to all these results, there were improvements in cisplatin induced testicular damage through attenuation of mitochondria mediated apoptosis, inflammation, and oxidative stress owing to resveratrol pretreatment. Thus, resveratrol, as a potential therapeutic agent, may hold promise in preventing mitochondria mediated apoptosis and inflammation in cisplatin-induced testicular damage in rats.

Cynara scolymus leaves extract alleviates nandrolone decanoate-induced alterations in testicular function and sperm quality in albino rats.

Nandrolone decanoate (ND) is a commonly used anabolic-androgenic steroid. These drugs are illegally self-administered by athletes to enhance their sports performance. However, their abuse could influence the testicular function and fertility. The main objective of this study was to evaluate the possible protective effects of Cynara scolymus leaf extract (CLE) on ND-induced testicular dysfunction in rats. Five groups of adult male rats (10 rats each) were used. Group I rats received only saline and served as controls. Group II rats were injected with a vehicle once weekly, while group III rats received intramuscular injections of ND (20mg/kg/week for 60days). Group IV rats orally received 1g/kg/day of CLE and group V rats received ND and CLE at the aforementioned doses. The results revealed that ND has a negative impact on the testicular function as evidenced by the significant increases (p ≤ 0.05) in testicular malondialdehyde concentration and serum non-prostatic acid phosphatase activity, as well as the significant decreases in serum testosterone levels, testicular weight, glutathione concentration, catalase enzyme activity, and total antioxidant capacity. These results were accompanied by considerable alterations of sperm characters and histopathological studies of the testicular tissue. However, co-treatment with CLE extract significantly alleviated (p ≤ 0.05) almost all ND-induced pathological alterations. In conclusion, co-treatment of ND-intoxicated rats with CLE ameliorated the toxic effects of ND on the testicular structure and function, probably due to its antioxidant activity.

Effect of tramadol dependence on male sexual dysfunction.

Tramadol dependence became an increasing and alarming problem in the Egyptian community. Wide availability of tramadol as a pain killer and its role in the treatment of premature ejaculation may be the most apparent causes of increased magnitude of the problem among youth who believe that tramadol has a positive impact on their sexual functions. This study aimed to explore the real impact of chronic tramadol administration on sexual functions in males dependent on tramadol. The study was carried on 80 subjects (50 subjects were tramadol dependent group and 30 subjects represented the control group). Personal, family and past histories were obtained from all the participants in addition to the toxicological history from tramadol dependent group. Urine screening for tramadol was done for all cases of history of tramadol dependence then confirmation by HPLC technique to measure tramadol blood level was done. Both groups were investigated for serum testosterone and prolactin level. Curiosity (22%) and treatment of premature ejaculation (20%) were the main motives for dependence. Erectile dysfunction and decreased libido occurred in 44% and 48% of tramadol dependent group respectively. Significant increase in erectile dysfunction and decreased libido was noted as the duration of dependence increased. Additionally, significant decrease in serum testosterone level and increase in serum prolactin level as tramadol daily dose and duration increased was found. In conclusion, men who take tramadol for premature ejaculation or any other purpose must know that they are very susceptible to many sexual dysfunctions.

The effect of chronic stress on the testis of adult albino Rats and the possible protective effect of astaxanthin supplementation (Histological, immunohistochemical and biochemical studies)

Background and Objectives: Stress can disrupt homeostasic balance within the organisms. Chronic stress can have damaging effects on the whole organism. The present study aimed to throw more light on themolecular,immunological and histological alterations in adult albino rat’s testis subjected to chronic stress and to demonstrate whether the potential chronic stress‑induced testicular alterations could be ameliorated by astaxanthin or not.Materials and Methods: Forty healthy adult male albino rats were used in this study, they were assigned as 3 main groups: Group I (Control group) which are subdivided into two equal groups, Group II (stress group) rats were restrained for 1 h and after 4 hs they are forced to swim for 15 minutes every day for 6 months, and Group III (protective group) rats were subjected to stressors as previous group in concomitant with daily administration of astaxanthin (25mg/kg b.w.) dissolved in 1ml normal saline in a single daily doseorally in a single daily dose. Blood samples and testicular tissues were collected and assayed for histological, immunohistochemical and biochemical changes.Results: The results of the present study demon‌strated thatthere were degenerative changes in spermatogenic and Sertoli cells of stress group and were associated with statistical significant reduction in height of germinal epithelium, Ki-67 and vimentinimmunoexpression.These changes were observed to be reduced in astaxanthin protected group.Also,there was a decrease in serum testosterone levels in stress group, which were normalized after astaxanthin administration. Also, stress significantly increased the serum levels of malondialdehyde, and decreased levels of total antioxidant capacity TAC.Conclusions: This study concluded that astaxanthin has beneficial protective effects against the deleterious effects of chronic stress on the testis. Therefore, it may be a suitable nutrional supplement in alleviating some negative aspects of chronic stress effects on testis.

Progranulin Protects Rat Testis From Ischaemic Reperfusion Injury

Abstract Background: Ischemic reperfusion (I/R) damage of the testis is a common problem, it is mainly caused by testicular torsion and detorsion. Progranulin (PGRN) has been reported to have prominent anti-inflammatory and protective effects on I/R injury in the heart, brain and kidney, however, its effects on testicular I/R lesion have not been evaluated. Aim of Study: To examine the effects of progranulin on rat testicular ischaemia/reperfusion induced by torsion/ detor-sion and the possible underlying mechanisms. Material and Methods: In this study, rats were divided into 4 groups: (i) Sham; (ii) Testicular ischemia/reperfusion (I/R), 2h of ischemia followed by 6 h of reperfusion; (iii) I/R treated by PGRN (0.01mg/rat) administered 1.5h after the induction of ischaemia. (iv) I/R treated by PGRN (0.1mg/rat) administered 1.5h after development of ischemia. At the end of the study, some testicular oxidative stress markers, inflam-matory, apoptotic markers and serum testosterone were meas-ured, in addition to histopathologic study. Results: Significant decreases in serum testosterone levels, testicular superoxide dismutase (SOD) and glutathione per-oxidase (Gpx) activity with increase in tissue malondialdehyde (MDA) were observed in I/R group when compared with controls. These antioxidant levels were increased in PGRN treated groups with significant decrease in MDA levels. While an increase in tumor necrosis factor-alpha (TNF-a), IL-1b, caspase-8 and caspase-3 levels were found in the torsion/ detorsion group, significant decrease in the levels of these inflammatory cytokines and apoptotic markers were observed in PRGR treated groups in a dose dependent maner. Conclusion: These results demonstrate that PGRN signif-icantly produced protective effects on testicular tissue damage through antioxidant, anti-inflammatory and antiapoptotic mechanisms.

Association between polychlorinated biphenyl 153 exposure and serum testosterone levels: analysis of the National Health and Nutrition Examination Survey.

To examine the effects of environmental polychlorinated biphenyls (PCBs) 153 exposure, an industrial plasticizer, on serum testosterone levels. Using data collected from the 1999-2000 and 2001-2002 National Health and Nutrition Examination Survey (NHANES), we analyzed serum total testosterone and PCB153 levels, demographic data and comorbidities for men aged 18 years and older. Univariate and multivariate linear regression analysis was used to evaluate the association between total testosterone and serum PCB153. Five hundred and fifty-seven men met inclusion criteria. Median age was 45.7 [33.4-60.4] years old while median serum total testosterone and PCB153 levels were 479 [352.5-607] ng/dL and 0.20 [0.11-0.39] ng/g, respectively. Increasing age, higher body mass index (BMI), higher levels of serum PCB153, lower levels of activity and a history of diabetes mellitus and coronary heart disease were associated with decreasing serum testosterone levels on univariate linear regression. On multivariate linear regression, increasing age (estimate -6.29 ng/dL per year of life, P<0.001) and BMI (estimate -7.08 ng/dL per unit BMI, P<0.001) were associated with declining serum testosterone levels. While serum PCB153 levels were found to be negatively correlated with serum testosterone levels on univariate analysis (estimate -179.67, P<0.001), this association was not significant on the multivariable model (estimate -12.83, P=0.673). In this population-based analysis, we report an association between a decrease in serum testosterone with increasing serum levels of PCB153. Identifying environmental factors for etiology of low testosterone and mechanisms for causation will be important to aid in strategies to increase testosterone naturally in men.

Analysis of testosterone pathway genes in dogs (78,XY; SRY-positive) with ambiguous external genitalia revealed a homozygous animal for 2-bp deletion causing premature stop codon in HSD17B3.

The genetic background of disorders of sex development (DSD) in dogs with a normal male sex chromosome set (78,XY) is poorly described. In this study, we present for the first time, an analysis of six genes of the testosterone pathway, encoding enzymes (CYP17A1, HSD3B2, HSD17B3, SRD5A2) and transcription factors (NR5A1, AR). The entire coding sequence and flanking regions of the introns, 5'-UTR and 3'-UTR were analyzed in five DSD dogs (78,XY, SRY-positive) with ambiguous external genitalia and in 15 control dogs. A homozygous deletion of 2bp in exon 2 of HSD17B3 (hydroxysteroid 17-beta dehydrogenase 3) was found in a Dachshund dog with enlarged clitoris, vulva and abdominal gonads and decreased serum testosterone level. In silico analysis revealed that this deleterious variant causes truncation of the encoded polypeptide (from 306 to 65 amino acids) and deprivation of the active site of the encoded enzyme. Genotyping of 23 control Dachshund dogs showed a normal homozygous genotype. Thus, we assumed that the 2-bp deletion is the causative variant. Moreover, 24 SNPs (four in CYP17A1, three in HSD3B2, six in HSD17B3, five in SRD5A2, one in AR and five in NR5A1), two intronic indels (one in HSD3B2 and one in SRD5A2) and two microsatellite polymorphisms in exon 1 of AR were found. Six SNPs appeared to be novel. No association with DSD phenotype was observed. Identification of the first case of DSD in domestic animals caused by a deleterious variant of a gene involved in testosterone synthesis showed that these genes are important candidates in such studies.

Curcumin protects against palmitic acid-induced apoptosis via the inhibition of endoplasmic reticulum stress in testicular Leydig cells

BackgroundPalmitic acid (PA) is a common saturated fatty acid that induces apoptosis in various types of cells, including testicular Leydig cells. There is evidence suggesting that PA is increased in patients with obesity and that PA-induced cell apoptosis may play an important role in obesity-related male infertility. Curcumin, a natural polyphenol, has been reported to exert cytoprotective effects in various cell types. However, the cytoprotective effect of curcumin against PA-induced apoptosis in Leydig cells remains unknown. Therefore, the current study was performed to investigate the protective effects of curcumin in response to PA-induced toxicity and apoptosis in murine Leydig tumor cell line 1 (MLTC-1) cells and explore the mechanism underlying its anti-apoptotic action.MethodsMLTC-1 cells were cultured in Roswell Park Institute-1640 medium and divided into five groups. First four groups were treated with 50–400 μM PA, 400 μM PA + 5–40 μM curcumin, 400 μM PA + 500 nM 4-phenylbutyric acid (4-PBA, an endoplasmic reticulum (ER) stress inhibitor), and 500 nM thapsigargin (TG, an ER stress inducer) + 20 μM curcumin, respectively, followed by incubation for 24 h. Effects of PA and/or curcumin on viability, apoptosis, and ER stress in MLTC-1 cells were then determined by cell proliferation assay, flow cytometry, and western blot analysis. The fifth group of MLTC-1 cells was exposed to 400 μM of PA and 5 IU/mL of human chorionic gonadotropin (hCG) for 24 h in the absence and presence of curcumin, followed by measurement of testosterone levels in cell-culture supernatants by enzyme-linked immunosorbent assay (ELISA). Rats fed a high-fat diet (HFD) were treated with or without curcumin for 4 weeks, and the testosterone levels were detected by ELISA.ResultsExposure to 100–400 μM PA reduced cell viability, activated caspase 3, and enhanced the expression levels of the apoptosis-related protein BCL-2-associated X protein (BAX) and ER stress markers glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in MLTC-1 cells. Treating cells with 500 nM 4-PBA significantly attenuated PA-induced cytotoxicity through inhibition of ER stress. Curcumin (20 μM) significantly suppressed PA- or TG-induced decrease in cell viability, caspase 3 activity, and the expression levels of BAX, CHOP, and GRP78. In addition, treating MLTC-1 cells with 20 μM curcumin effectively restored testosterone levels, which were reduced in response to PA exposure. Similarly, curcumin treatment ameliorated the HFD-induced decrease in serum testosterone level in vivo.ConclusionsThe present study suggests that PA induces apoptosis via ER stress and curcumin ameliorates PA-induced apoptosis by inhibiting ER stress in MLTC-1 cells. This study suggests the application of curcumin as a potential therapeutic agent for the treatment of obesity-related male infertility.

Role of the gene Phlda1 in fenvalerate-induced apoptosis and testicular damage in Sprague-Dawley rats

ABSTRACTFenvalerate (FEN), a pyrethroid insecticide used worldwide, has been shown to produce a potentially adverse effect on male reproduction. However the mechanisms are not completely understood. Thus this study aimed to (1) determine whether cellular apoptosis was involved in FEN-induced testicular damage in rats, and (2) identify the potential mechanism involved in FEN-induced apoptosis in testes. Data demonstrated that FEN markedly decreased serum testosterone levels, increased the inner diameter of seminiferous tubules, decreased the layers of spermatogenic cells, disturbed spermatogenesis and increased the number of apoptotic cells. Further, bioinformatic analysis of gene microarray in rat testis tissue showed that FEN significantly altered the expressions of genes (Krt8, Mal, Cd24, Lcn2, Phlda1, Arg2) related to apoptotic related processes. The expression pattern of these 6 genes was upregulated in FEN-treated rat testicular tissue. qRT-PCR analysis demonstrated that Phlda1, a well-documented pro-apoptotic factor, was significantly elevated by FEN. The expression of PHLDA1 testicular protein was also elevated following FEN exposure. In conclusion, our results suggest that FEN exposure induced deleterious effects on rat testes associated with Phlda1-mediated apoptosis which may act as a molecular mechanism underlying FEN induced rat testicular damage.

Chronological Molecular Changes in Neuronal Communication in Androgen-Deficient Rats.

We investigated the early onset of molecular changes in the hippocampus of orchidectomy (ODX)-induced androgen-deficient rats. Transcript levels of the genes associated with loss of synaptic plasticity (Bdnf, Syn, GluN1, α7-nAChR, and M1-mAChR), formation of neurofibrillary tangles (Tau4 and Tau3), and amyloid plaques (App, Adam10, and Bace1), in the hippocampus of rats at 0, 1, 3, 6, and 9days after ODX (D0, D1, D3, D6 and D9, respectively) were determined. Primarily, the sudden loss of androgen, as confirmed by the decreased serum testosterone levels and accessory sex organ weights, induced a chronological reduction in Syn (at D1), and increase in GluN1 (at D3), α7-nAChR, and M1-mAChR (at D6) and a decrease in Bdnf (at D9) transcript levels. Tau4 and Tau3 mRNA levels were increased at D6 and D9, respectively. No changes in App, Adam10, and Bace1 mRNA levels were detected within the 9-day study period. To confirm those changes were caused by androgen deprivation and not increasing age, the mRNA expression levels of those genes in 9-day orchidectomized rats (ODX-D9) were compared with age-matched intact rats. All changes of mRNA expression levels of the ODX-D9 rats were aligned with the D9 rats, except for GluN1 that was decreased in the ODX-D9 rats. Moreover, the total and phosphorylated tau protein levels were increased in the ODX-D9 rats. These results denote that androgen deficiency induces the early onset of neurodegeneration, while the loss of synaptic plasticity together with the formation of neurofibrillary tangles could be used as markers for neurodegenerative prediction.

Paraquat exposure delays stem/progenitor Leydig cell regeneration in the adult rat testis

Paraquat, a widely used nonselective herbicide, is a serious hazard to human health. However, the effects of paraquat on the male reproductive system remain unclear. In this study, adult male Sprague Dawley rats were intraperitoneally injected ethane dimethane sulfonate (EDS, 75 mg/kg) to initiate a regeneration of Leydig cells. EDS-treated rats were orally exposed to paraquat (0.5, 2, 8 mg/kg/day) from post-EDS day 17 to day 28 and effects of paraquat on Leydig and Sertoli cell functions on post-EDS day 35 and day 56 were investigated. Paraquat significantly decreased serum testosterone levels at 2 and 8 mg/kg. Paraquat lowered Leydig cell Hsd17b3, Srd5a1, and Hsd11b1 mRNA levels but increased Hsd3b1 on post-EDS day 35. Paraquat lowered Cyp11a1, Cyp17a1, and Hsd11b1 but increased Srd5a1 on post-EDS day 56. However, paraquat did not alter Leydig cell number and PCNA labeling index. Epididymal staining showed that few sperms were observed in paraquat-treated rats. Primary culture of adult Leydig cells showed that paraquat diminished testosterone output and induced reactive oxygen species generation at 1 and 10 μM and apoptosis rate at 10 μM. In conclusion, a short-term exposure to paraquat delays Leydig cell regeneration from stem/progenitor Leydig cells, causing low production of testosterone and an arrest of spermatogenesis.

Nano-selenium attenuates nickel-induced testosterone synthesis disturbance through inhibition of MAPK pathways in Sprague-Dawley rats.

The aim of this study was to investigate the protective effects of Nano-Se against Ni-induced testosterone synthesis disorder in rats and determine the underlying protective mechanism. Sprague-Dawley rats were co-treated with Ni (5.0 mg/kg, i.p.) and Nano-Se (0.5, 1.0, and 2.0 mg/kg, oral gavage) for 14 days after which various endpoints were evaluated. The Ni-induced abnormal pathological changes and elevated 8-OHdG levels in the testes were attenuated by Nano-Se administration. Importantly, decreased serum testosterone levels in the Ni-treated rats were significantly restored by Nano-Se treatment, particularly at 1.0 and 2.0 mg/kg. Furthermore, the mRNA and protein levels of testosterone synthetase were increased by Nano-Se compared to the Ni group, whereas phosphorylated protein expression levels of mitogen-activated protein kinase (MAPK) pathways were suppressed by Nano-Se administration in the Ni-treated rats. Overall, the results suggest that Nano-Se may ameliorate the Ni-induced testosterone synthesis disturbance via the inhibition of ERK1/2, p38, and JNK MAPK pathways.

Is there a relationship between varicocele and testosterone levels?

Objectives The goal of this work was to study the relationship between presence of varicocele and testosterone serum levels in adulthood. Methods A comparative, cross-sectional study of 387 men who consulted for erectile dysfunction. Age, body mass index (BMI), diabetes (DM), and presence of varicocele were related to testosterone levels through uni- and multi-variate analysis. Results A total of 248 cases (70.8%) had no varicocele, 46 (13.1%) had grade I varicocele, 36 (10.3%) grade II, and 20 (5.7%) grade III. The mean total testosterone levels were 4.77 ng/mL in the non-varicocele group and 4.34 ng/mL in the varicocele group (p = .91), while free testosterone levels were 69.81 and 73.24 pg/mL (p = .18), respectively. In the multivariate analysis, BMI> = 30 was related to low total testosterone levels (OR: 2.94, p < .001) and low free testosterone (OR: 2.01, p = .01), while advanced age associated with low levels of free testosterone (OR: 1.04, p < .001). Conclusions We were not able to establish a relationship between the presence of varicocele and decreased serum testosterone levels. Other factors already described, such as obesity and age, were related to low levels of total and free testosterone.

Effects of perfluorooctanoic acid on stem Leydig cell functions in the rat

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic (PFOS) are two perfluorinated chemical products widely existing in the environment. Evidence suggested that PFOA might relate to male reproductive dysfunction in rats and humans. PFOA exposure inhibited the function of Leydig cells. However, it is still unknown whether PFOA affects stem Leydig cells (SLCs). In the present study, we examined the effects of a short-term exposure to PFOA on Leydig cell regeneration and also explored the possible mechanism involved. Thirty-six adult Sprague-Dawley rats were randomly divided into three groups and intraperitoneally injected with a single dose of 75 mg/kg ethane dimethyl sulfonate (EDS) to eliminate all Leydig cells. From post-EDS day 7, the 3 group rats received 0, 25 or 50 mg/kg/day PFOA (n = 12 per group) for 9 consecutive days. Exposure to PFOA significantly decreased serum testosterone levels by day 21 and day 56 post-EDS treatment. Also, the expression levels of Leydig cell specific genes (Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Hsd11b1 and Cyp17a1) and their protein levels were all down-regulated. PFOA exposure may also affect proliferation of SLCs or their progeny since the numbers of PCNA-positive Leydig cells were reduced by post-EDS day 21. These in vivo observations were also confirmed by in vitro studies where the effects of PFOA were tested by culture of seminiferous tubules. In summary, PFOA exposure inhibits the development of Leydig cells, possibly by affecting both the proliferation and differentiation of SLCs or their progeny.

Resveratrol and dimethyl fumarate ameliorate testicular dysfunction caused by chronic unpredictable mild stress-induced depression in rats

Chronic stress is a major factor contributing to male infertility. Increasing evidence has demonstrated that resveratrol or dimethyl fumarate (DMF) has antioxidant and anti-inflammatory functions. Our study aimed to evaluate the protective effects of resveratrol or DMF against testicular dysfunction associated with chronic unpredictable mild stress (CUMS)-induced depression in rats. Rats were subjected to 8 weeks of CUMS to induce depressive−like symptoms. CUMS-induced depressive-like behaviours in rats were evidenced by increased serum corticosterone levels and decreased serum and hippocampal serotonin levels as well as decreased hippocampal BDNF levels. CUMS significantly reduced sucrose preference and increased immobility time in stressed rats. Furthermore, CUMS exposure resulted in a significant decrease in serum testosterone levels and testicular expression of steroidogenic acute regulatory protein (StAR), cytochrome P450 side chain cleavage (CYP450scc) enzyme and C-kit. CUMS significantly decreased and increased testicular expression of β-catenin and GSK-3β, respectively. CUMS also resulted in a significant increase in testicular expression of NF-κB, TNF-α, IL-Iβ, and Bax and decreased Bcl-2 expression levels. CUMS increased testicular MDA levels and significantly decreased testicular GSH and serum total antioxidant capacity levels. The histopathological results provided evidence for the biochemical and molecular analyses. All of these effects were significantly ameliorated by the administration of resveratrol or DMF. In conclusion, our study reveals that resveratrol or DMF exert profound testicular protective effects in CUMS rats that are mediated in part by suppressing oxidative stress, inflammation, and apoptosis leading to the upregulation of serum testosterone levels, and testicular StAR, CYP450scc, c-kit and β-catenin levels.

Protective Antioxidant Effects of N-acetylcysteine on Testicular Tissue and Serum Testosterone in Paranonylphenol-Treated Mice (A Stereological Analysis)

Paranonilphenol (p-NP) is an environmental pollutant that affects the male reproductive system through induction of oxidative stress. The aim of this study was to evaluate the protective effects of N-acetylcysteine (NAC) as an antioxidant against impairment of testicular tissue caused by p-NP. In this study, 24 adult male NMRI mice were randomly divided into 4 groups (n=6 each groups): 1-Control, 2- p-NP (250 mg/kg/day), 3-NAC (150 mg/kg/day) and 4-p-NP+NAC. After 35 days of orally treatment a significant decrease in the diameter (P<0.01), germinal epithelium height (P<0.04), basement membrane thickness and volume of seminiferous tubules (P<0.02) and as well as a significant decrease in serum testosterone level (P<0.04) were observed. Also a significant decrease in the count of sertoli (P<0.04), leydig (P<0.02), spermatogonia (P<0.04), spermatocyte (P<0.04), round and long spermatid (P<0.02) cells in the p-NP group compared to other group were observed. In the p-NP group, atrophy, edema, reduction in lumens sperm density and vacuoled were observed. While in this group a significant increase in the interstitial tissue volume (p<0.01), level of testis MDA (p<0.01) and count of the positive-TUNEL cells (p<0.01) in the seminiferous tubules were observed. NAC can significantly compensate the parameters mentioned above in NAC +p-NP group compared to the p-NP group. The findings of this study showed that NAC, as a potent antioxidant, can compensate the adverse effects of p-NP on testicular tissue.