stilbenes and Infertility--Male

The aim of this study was to investigate the protective action of resveratrol against the reproductive damage caused by left-sided experimental varicocele. There was a reduction of testicular major axis in the varicocele group when compared with the other groups; the testicular volume was reduced in varicocele group in comparison to the sham-control and resveratrol groups. The frequency of morphologically abnormal sperm was higher in varicocele and varicocele treated with resveratrol groups than in sham-control and resveratrol groups. The frequency of sperm with 100% of mitochondrial activity and normal acrosome integrity were lower in varicocele group than in varicocele treated with resveratrol, sham-control and resveratrol groups. Sperm motility was also reduced in varicocele group than in other groups. The sperm DNA fragmentation was higher in varicocele group than in other groups. Testicular levels of malondialdehyde were higher in varicocele and varicocele treated with resveratrol groups. The varicocele and varicocele treated with resveratrol groups had a significantly higher frequency of TUNEL-positive cells than sham-control and resveratrol groups; however, immunolabeling of the testes from varicocele treated with resveratrol group showed a lower number of apoptotic germ cells in comparison with the left testis of rats of the varicocele group. Reproductive alterations produced by varicocele from peripuberty were reduced by resveratrol in adulthood. Resveratrol should be better investigated as an adjuvant in the treatment of varicocele. Daily administration of resveratrol to rats with varicocele from peripuberty improves sperm quality in the adulthood.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Infertility, Male; Male; Puberty; Rats; Rats, Wistar; Reproduction; Resveratrol; Sperm Motility; Stilbenes; Testis; Varicocele

Benzo(a)pyrene [B(a)P] is an environmental toxicant that alters the steroidogenic profile of testis and induces testicular dysfunction. In the present study, we have investigated the molecular signaling of B(a)P and the ameliorative potential of the natural aryl hydrocarbon receptor (AhR) antagonist and antioxidant, resveratrol, on B(a)P-induced male reproductive toxicity. Studies showed that B(a)P treatment resulted in p38 MAPK activation and increased inducible nitric oxide synthase (iNOS) production along with testicular apoptosis and steroidogenic dysfunction. Resveratrol cotreatment maintained testicular redox potential, increased serum testosterone level and enhanced expression of major testicular steroidogenic proteins (CYPIIA1, StAR, 3βHSD, 17βHSD) and prevented subsequent onset of apoptosis. Resveratrol cotreatment resulted inhibition of testicular cytochrome P4501A1 (CYP1A1) expression, which is the major B(a)P metabolizing agent for BPDE-DNA adduct formation. Resveratrol also significantly decreased the B(a)P-induced AhR protein level, its nuclear translocation and subsequent promoter activation, thereby decreased the expression of CYP1A1. Resveratrol also down-regulated B(a)P-induced testicular iNOS production through suppressing the activation of p38 MAPK and ATF2, thus improved the oxidative status of the testis and prevented apoptosis. Our findings cumulatively suggest that resveratrol inhibits conversion of B(a)P into BPDE by modulating the transcriptional regulation of CYP1A1 and acting as an antioxidant thus prevents B(a)P-induced oxidative stress and testicular apoptosis.

Topics: Activating Transcription Factor 2; Active Transport, Cell Nucleus; Animals; Antioxidants; Apoptosis; Basic Helix-Loop-Helix Transcription Factors; Benzo(a)pyrene; Cytochrome P-450 CYP1A1; Dietary Supplements; Dose-Response Relationship, Drug; Environmental Pollutants; Gene Expression Regulation; Infertility, Male; Male; MAP Kinase Signaling System; Nitric Oxide Synthase Type II; Oxidative Stress; Promoter Regions, Genetic; Rats, Wistar; Receptors, Aryl Hydrocarbon; Resveratrol; Stilbenes; Testis; Testosterone

Male infertility is a complex, multifactorial and polygenic disease that contributes to ~50% cases of infertility. Previous studies have demonstrated that excess weight and obesity factors serve an important role in the development of male infertility. An increasing number of studies have reported that resveratrol may regulate the response of cells to specific stimuli that induce cell injury, as well as decrease germ cell apoptosis in mice or rats. In the present study, the semen quality and serum sex hormone levels were evaluated in 324 men, which included 73 underweight, 82 normal weight, 95 overweight and 74 obese men. All patients were referred to The Reproductive Medicine Center of Shanxi Women and Infants Hospital (Taiyuan, China) between January 2013 and January 2015. The aim of the present study was to investigate the effects of resveratrol treatment on the motility, plasma zinc concentration and acrosin activity of sperm from obese males. The sperm concentration, normal sperm morphology, semen volumes, DNA fragmentation rates and testosterone levels in men from the overweight and obese groups were markedly decreased when compared with men in the normal weight group. In addition, the progressive motility, seminal plasma zinc concentration and spermatozoa acrosin activity were notably decreased in the obese group compared with the normal weight group. However, estradiol levels were significantly increased in the overweight, obese and underweight groups compared with the normal weight group. Notably, semen samples from obese males with astenospermia treated with 0‑100 µmol/l resveratrol for 30 min demonstrated varying degrees of improvement in sperm motility. When these semen samples were treated with 30 µmol/l resveratrol, sperm motility improved when compared to other doses of resveratrol. Therefore, 30 µmol/l resveratrol was selected for further experiments. Upon treatment of semen samples with resveratrol (30 µmol/l) for 30 min, the seminal plasma zinc concentration and spermatozoa acrosin activity increased significantly in the experimental group compared with the control group. These data suggest that male obesity negatively impacts on male reproductive potential, not only through altering hormone levels, but also by directly altering sperm function. In addition, resveratrol may have a therapeutic and protective effect against obesity-induced abnormalities in semen.

Topics: Acrosin; Adult; Cell Survival; Cytoplasm; Gonadal Steroid Hormones; Humans; Infertility, Male; Male; Obesity; Overweight; Protective Agents; Resveratrol; Semen Analysis; Spermatozoa; Stilbenes; Zinc

This study was performed to investigate the protective and therapeutic effects of resveratrol (RES) against CdCl2-induced toxicity in rat testes. Seven experimental groups of adult male rats were formulated as follows: A) controls+NS, B) control+vehicle (saline solution of hydroxypropyl cyclodextrin), C) RES treated, D) CdCl2+NS, E) CdCl2+vehicle, F) RES followed by CdCl2 and M) CdCl2 followed by RES. At the end of the protocol, serum levels of FSH, LH and testosterone were measured in all groups, and testicular levels of TBARS and superoxide dismutase (SOD) activity were measured. Epididymal semen analysis was performed, and testicular expression of Bcl-2, p53 and Bax was assessed by RT-PCR. Also, histopathological changes of the testes were examined microscopically. Administration of RES before or after cadmium chloride in rats improved semen parameters including count, motility, daily sperm production and morphology, increased serum concentrations of gonadotropins and testosterone, decreased testicular lipid peroxidation and increased SOD activity. RES not only attenuated cadmium chloride-induced testicular histopathology but was also able to protect against the onset of cadmium chloride testicular toxicity. Cadmium chloride downregulated the anti-apoptotic gene Bcl2 and upregulated the expression of pro-apoptotic genes p53 and Bax. Resveratrol protected against and partially reversed cadmium chloride testicular toxicity via upregulation of Bcl2 and downregulation of p53 and Bax gene expression. The antioxidant activity of RES protects against cadmium chloride testicular toxicity and partially reverses its effect via upregulation of BCl2 and downregulation of p53 and Bax expression.

Topics: Animals; Antioxidants; bcl-2-Associated X Protein; Cadmium Chloride; Drug Interactions; Follicle Stimulating Hormone; Gene Expression Regulation; Gonadotropins; Histocytochemistry; Infertility, Male; Luteinizing Hormone; Male; Proto-Oncogene Proteins c-bcl-2; Random Allocation; Rats, Wistar; Resveratrol; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stilbenes; Superoxide Dismutase; Testis; Testosterone; Thiobarbituric Acid Reactive Substances; Tumor Suppressor Protein p53

Cryopreservation of human semen can cause DNA damages, which compromise the fertilization and normal embryo development. The present study showed that the antioxidant resveratrol prevents these damages both in fertile and infertile men. The addition of ascorbic acid before cryopreservation can reduce DNA damages only in infertile men. Although further studies are needed, the present work showed that resveratrol could be considered in human cryopreservation procedures to avoid/minimize DNA damages and preserve sperm integrity.

Topics: Adult; Antioxidants; Ascorbic Acid; Cryopreservation; DNA Damage; Humans; In Vitro Techniques; Infertility, Male; Male; Resveratrol; Semen Preservation; Stilbenes

To analyze oxidative stress markers and seminal standard parameters after using resveratrol (0.1, 1.0, and 10.0 mM), an important antioxidant, in the cryopreservation of human semen.. In vitro prospective study.. Institutional study.. Infertile and fertile men.. None.. Levels of thiobarbituric acid-reactive species (TBARS), superoxide dismutase (SOD), and catalase (CAT) activities and spermatozoa concentration, motility, and morphology.. Increased TBARS levels were observed in the post-thawing semen in both fertile and infertile men. Infertile men had lower CAT and SOD activities in prefreezing and post-thawing samples when compared with fertile men. The addition of resveratrol in all the concentrations assayed was able to prevent post-thawing lipoperoxidation in both fertile and infertile men. However, this effect was not dose dependent. The cryopreservation process was not able to change sperm concentration or morphology. However, a decrease in sperm motility was observed in both the fertile and infertile men. The addition of resveratrol was not able to prevent this effect.. Resveratrol avoids oxidative damages induced by the cryopreservation of human semen, but it is not able to restore the decrease in sperm motility.

Topics: Adult; Antioxidants; Catalase; Cryopreservation; Cryoprotective Agents; Humans; Infertility, Male; Male; Oxidative Stress; Reactive Oxygen Species; Resveratrol; Semen; Semen Analysis; Semen Preservation; Stilbenes; Young Adult

The aim of this study was to analyse the multigenerational effects of para-nonylphenol (NP) and resveratrol (RES) on the body weight, organ weight and reproductive fitness of outbred CD-1 mice. The data indicate that in male mice, NP had an effect on the weight of selected reproductive organs and the kidneys in the parental (P) generation males. Effects on selected reproductive organs, the liver and kidneys in the F1-generation males were also seen. In females, effects of NP on body weight and kidney weight were seen in the P generation, but no effects on any measured parameter were seen in the F1 generation. RES had no effect on body weight but did have some effect on selected male and female reproductive organs in the P generation. RES altered the spleen and liver weights of P-generation males and the kidney weight of F1-generation males. Acrosomal integrity (using a monoclonal antibody against intra-acrosomal sperm proteins) was assessed for both generations of NP- and RES-treated mice. A significant reduction in acrosomal integrity was seen in both generations of NP-treated, but not in RES-treated, mice. Fewer offspring were observed in the second litter of the F2 generation of mice treated with NP; no similar effect was seen in RES-treated mice. The litter sex ratio was not different from controls. Unlike RES, NP had a negative effect on spermatogenesis and sperm quality with a resultant impact on in vivo fertility.

Topics: Acrosome; Animals; Animals, Outbred Strains; Body Weight; Environmental Pollutants; Female; Fertility; Genitalia, Female; Genitalia, Male; Infertility, Male; Isoflavones; Kidney; Litter Size; Liver; Male; Mice; Organ Size; Ovarian Follicle; Phenols; Phytoestrogens; Plant Preparations; Pregnancy; Resveratrol; Sex Ratio; Spermatogenesis; Stilbenes

Application of the techniques of epidemiology and clinical toxicology has accelerated study of the reproductive effects of toxic chemical and physical exposures in the workplace. Three examples of work in progress are included in the present communication. The first concerns 1,2-dibromo-3-chloropropane, a known cause of male sterility, which continues to be used as a nematocide in Hawaii. Occupational exposures of Hawaiian agricultural workers to airborne 1,2-dibromo-3-chloropropane are mainly in the range of parts per billion. A prospective study of pineapple field workers has been undertaken to evaluate sperm counts and morphology before, during, and after 1,2-dibromo-3-chloropropane application. To date, no sperm count depression is evident at this level of exposure. The second example involves a cluster of seven spontaneous abortions in female office workers exposed to video display terminals. The cluster has been analyzed with the use of fetal life tables. Excess incidence was confirmed (p = 0.0045), but no etiology was determined. The findings may have been due to chance. The third example pertains to male chemical workers manufacturing diaminostilbene, an optical brightener, and the workers' reported sexual impotence. Impotence was confirmed in 7 of 29 workers by questionnaire and suggested for another 7. Serum testosterone analyses found depressed values (less than 300 mg/ml) in 8 of 28 exposed workers. The luteinizing hormone and follicular stimulating hormone levels were generally normal.

Topics: Abortion, Spontaneous; Data Display; Environmental Health; Erectile Dysfunction; Female; Humans; Infertility, Male; Male; National Institute for Occupational Safety and Health, U.S.; Pregnancy; Propane; Reproduction; Stilbenes; United States

Topics: Animals; Clomiphene; Fertility; Gonadotropins, Pituitary; Hypothalamo-Hypophyseal System; Infertility, Male; Leydig Cells; Male; Rats; Spermatozoa; Stilbenes; Testis

Topics: Androgens; Clomiphene; Gonadotropins; Infertility, Male; Isoniazid; Male; Stilbenes; Vasodilator Agents