Apoptosis is characterized by a variety of changes resulting in the recognition and phagocytosis of apoptotic cells. Caspases (cysteinyl aspartate-specific proteinases) play a central role in the regulation of apoptosis in the human seminiferous epithelium. They are expressed as inactive proenzymes and participate in a cascade triggered in response to pro-apoptotic signals. To date, 14 caspases have been implicated in the human apoptotic pathway cascade. Among these, caspase-3 is considered to be a major executioner protease. Since apoptosis is a universal suicide system in almost all cells, a close control via molecular, endocrine and physical factors establishes homeostasis of cell growth and death. The proper regulation of the caspase cascade plays an important role in sperm differentiation and testicular maturity. However, caspases have been implicated in the pathogenesis of multiple andrological pathologies such as impaired spermatogenesis, decreased sperm motility and increased levels of sperm DNA fragmentation, testicular torsion, varicocele and immunological infertility. Future research may provide a better understanding of the regulation of caspases, which may help us to manipulate the apoptotic machinery for therapeutic benefits. In this review, we summarize the consequences of caspase activation, aiming to clarify their role in the pathogenesis of male infertility.

/pdf/role-of-caspases-in-male-infertility-15pmjprg9v.pdf

Role of caspases in male infertility

Alcohol drinking has been extensively studied in relation to prostate cancer, yet findings on the direction of the association are equivocal. Previous studies have not examined drinking patterns. Thus, the authors prospectively evaluated the associations between these factors and risk of incident prostate cancer (n = 2,479) in a cohort study of 47,843 US men (1986-1998). The men completed a questionnaire at baseline that included information on consumption of specific types of alcohol and frequency of use. The authors estimated hazard ratios using Cox proportional hazards regression for average alcohol intake and number of days per week on which alcohol was consumed stratified by average weekly intake ( or = 105 g/week). Compared with nondrinking, the hazard ratio for consumption increased slightly from an average of 5.0-14.9 g/day (hazard ratio (HR) = 1.05, 95% confidence interval (CI): 0.94, 1.18) to 30.0-49.9 g/day (HR = 1.13, 95% CI: 0.96, 1.33), but it was not increased at > or = 50 g/day (HR = 1.00, 95% CI: 0.77, 1.31) after adjustment for recent smoking and other factors. Compared with abstainers, risk was greatest among men who consumed an average of > or = 105 g/week but who drank on only 1-2 days per week (HR = 1.64, 95% CI: 1.13, 2.38). These results suggest that moderate or greater alcohol consumption is not a strong contributor to prostate cancer risk, except possibly in men who consume large amounts infrequently.

/pdf/alcohol-intake-drinking-patterns-and-risk-of-prostate-cancer-a89hv3jr1v.pdf

Alcohol Intake, Drinking Patterns, and Risk of Prostate Cancer in a Large Prospective Cohort Study

The Fas system is involved in the regulation of germ cell apoptosis associated with testicular injury in experimental animals exposed to various insults. We tested the hypothesis that enhanced germ cell apoptosis mediated by the up-regulation of the Fas system and the activation of caspases may be involved in ethanol-induced testicular injury. Adult Wistar rats were fed either ethanol in Lieber-DeCarli liquid diet or an isocaloric control diet for 12 weeks. Marked Sertoli cell vacuolization and germ cell degeneration were observed in the testes of ethanol-treated rats (ETR) by both light and electron microscopy. Enhanced apoptosis of germ cells in ETR was detected by the terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick end labelling (TUNEL) method, transmission electron microscopy, and was associated with elevated activity of caspase-3, -8 and -9. The expression levels of the Fas ligand (FasL) in Sertoli cells and of both Fas and caspase-3 in germ cells of ETR detected immunohistochemically were higher than those of the control testes. Furthermore, reverse transcriptase-polymerase chain reaction analysis demonstrated an increase in both Fas and FasL mRNA levels in ETR. Fas system up-regulation and the elevated activity of caspases in the testes of ETR may be a reflection of ethanol-induced testicular injury resulting in enhanced germ cells apoptosis, which may be involved in infertility associated with alcohol abuse.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2605.2002.00341.x

Involvement of Fas system and active caspases in apoptotic signalling in testicular germ cells of ethanol-treated rats.

Summary

The aim of this study was to investigate the effects of quercetin and fish n-3 fatty acids on the changes in testis induced by ethanol. Forty-five rats divided into five groups, control, ethanol, ethanol+quercetin, ethanol+fish n-3 fatty acids and ethanol+quercetin+fish n-3 fatty acids. At the end of 8 weeks, all the rats were sacrificed. Degenerative changes in histopathological analyses, the decreased body weight gain and seminiferous tubule diameters in ethanol group have been observed. TUNEL assay also showed an increase in apoptotic cell number. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), xanthine oxidase (XO) and testosterone levels were decreased as well as the levels of malondialdehyde (MDA) and nitric oxide (NO) were increased in ethanol group. Histopathological changes caused by ethanol have been improved by quercetin and fish n-3 fatty acids. It was also found that protection was provided by increasing SOD, CAT and GSH-Px activities in groups administered quercetin, fish n-3 fatty acids and quercetin+fish n-3 fatty acids, and by decreasing the levels of MDA and NO in groups administered both quercetin and fish n-3 fatty acids together. These results suggest that quercetin and fish n-3 fatty acids are beneficial agents to reduce testicular injury induced by ethanol except for testosterone levels.

Effects of quercetin and fish n-3 fatty acids on testicular injury induced by ethanol in rats

Zinc attenuates ethanol-induced Sertoli cell toxicity and apoptosis through caspase-3 mediated pathways.

The objective of the present study was to analyze the prospective alterations of the testis and epididymis in a defined strain of alcoholic rats in order to contribute to our understanding of the effects of chronic alcoholism on reproduction. The testis and epididymis of the animals were submitted to morphological analysis by macroscopy, light microscopy and electron microscopy and to morphometric analysis. The UCh rats showed atrophy of the epithelium and reduction of testis and epididymis weight, liver hypertrophy and fat infiltration and alterations of the hypothalamus-pituitary axis. Ethanol induces changes in the weight and in the epithelium of the testis and epididymis and in the hypothalamus-pituitary axis of the UCh rats.

Morphology of testis and epididymis in an ethanol-drinking rat strain (UChA and UChB).

Chronic alcoholism alters reproduction and therefore may be responsible for alterations of prostate and seminal vesicles, which are the subject of this analysis in UCh ethanol-drinking rats. The prostate and seminal vesicles of 20 animals were submitted to macroscopic, light microscopy, electron microscopy and morphometric analysis. The UCh rats showed atrophy of the epithelium and reduction of the weight of the prostate and seminal vesicle, liver hypertrophy and fat infiltration and alterations of the hypothalamus-pituitary axis. Ethanol induces changes in the weight and in the epithelium of prostate and seminal vesicles and hypothalamus-pituitary axis of UCh rats.

Morphology of the ventral lobe of the prostate and seminal vesicles in an ethanol-drinking strain of rats (UChA and UChB).

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Morphology of testis and epididymis in an ethanol-drinking rat strain (UChA and UChB).

Morphology of the ventral lobe of the prostate and seminal vesicles in an ethanol-drinking strain of rats (UChA and UChB).