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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been shown that lead (Pb) is able to induce lipid peroxidation, one of the main manifestations of oxidative stress. In this study we examined the relationship between chronic Pb exposure and level of reactive oxygen species (ROS) in reproductive system tissues of sexually mature male Wistar rats. One group of animals (control, K) was allowed to drink distilled water, the second group (Pb) was allowed to drink freely 1% aqueous solution of lead acetate. Another groups had a following supplements: rats were allowed to drink distilled water containing vitamin C (vit C) at concentration of 500 mg/l or Trolox (a vitamin E analog) at concentration of 48 mg/l or vit C (500 mg/l) + Trolox (48 mg/l). The similar groups among Pb-treated animals were examined after treatment with the same vitamins and using the same vitamin doses, dissolved in 1% aqueous solution of lead acetate. In all cases the time of drinking was 6 months. It was found that lead content in samples of tissues from testis, epididymis and in a whole blood in Pb- and Pb with antioxidants treated rats was significantly elevated. Chemiluminescence (CL) emitted by the Pb-treated tissues was significantly higher when compared to the light emission by tissues isolated from the animals of control group. The increase in the CL caused by lead occurs in the following increasing order within the studied tissues: cauda of epididymis < testis < caput of epididymis (19%, 39% and 51%, respectively). Dietary vit C supplementation to the Pb-treated rats for 6 months period decreased the CL from caput of epididymis, cauda of epididymis and testis (by 43%, 24%, 39%, respectively) more effectively in comparison to the control group (35%, 17%, 33%, respectively). Also stronger quenching effect on the light emission from the above mentioned tissues after Trolox supplementation was observed in the Pb-treated group (42%, 21%, 35%, respectively) than in the control group (23%, 13%, 13% respectively). The combination of both antioxidants treatments (vit C and Trolox) did not give a higher significant quenching effect compared to the treatment with the vitamins separately. No ultrastructural changes were found in the seminiferous epithelium of Pb-treated animals. However, we found abnormalities in ultrastructure of epididymal epithelial cells and epididymal spermatozoa in rats of Pb-treated groups. These findings provide ex vivo evidence that Pb causes oxidative cellular damage in reproductive system tissues of adult male rats, which may be closely associated with the ROS production.
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PMID:Detection of lead-induced oxidative stress in the rat epididymis by chemiluminescence. 1551

Advanced glycation end products (AGE)-modified proteins as well as oxidized-LDL (Ox-LDL) undergo receptor-mediated endocytosis by CHO cells overexpressing CD36, a member of class B scavenger receptor family. The purpose of the present study was to examine the effects of glycolaldehyde-modified BSA (GA-BSA) as an AGE-ligand and Ox-LDL on leptin expression in adipocytes. GA-BSA decreased leptin expression at both protein and mRNA levels in 3T3-L1 adipocytes and mouse epididymal adipocytes. Ox-LDL showed a similar inhibitory effect on leptin expression in 3T3-L1 adipocytes, which effect was protected by N-acetylcysteine, a reactive oxygen species (ROS) inhibitor. Binding of (125)I-GA-BSA or (125)I-Ox-LDL to 3T3-L1 adipocytes and subsequent endocytic degradation were inhibited by a neutralizing anti-CD36 antibody. Furthermore, this antibody also suppressed Ox-LDL-induced leptin down-regulation. These results clarify that the interaction of GA-BSA and Ox-LDL with CD36 leads to down-regulation of leptin expression via ROS system(s) in 3T3-L1 adipocytes, suggesting that a potential link of AGE- and/or Ox-LDL-induced leptin down-regulation might be linked to insulin-sensitivity in metabolic syndrome.
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PMID:Advanced glycation end products-modified proteins and oxidized LDL mediate down-regulation of leptin in mouse adipocytes via CD36. 1552 13

Glucose metabolism is necessary for successful fertilization in the mouse. Both spermatozoa and oocytes metabolize glucose through the pentose phosphate pathway (PPP), and NADPH appears required for gamete fusion. The aims of this study were to further characterize the utilization of glucose by the fertilizing spermatozoon and the fertilized oocyte, to demonstrate the importance of the PPP in different steps of fertilization, and to examine whether the beneficial effect of glucose could be mediated by a NADPH-dependent enzyme involved in redox regulation. By using a fluorescent analog of 2-deoxyglucose, glucose uptake was evidenced in both the head and flagellum of motile spermatozoa. After sperm-oocyte fusion, an increase in glucose uptake by the fertilized oocyte was observed but not before the formation of the male and female pronuclei. By using a microphotometric technique, activity of glucose 6-phosphate dehydrogenase (G6PDH), the key enzyme of the PPP, was localized to the sperm head and midpiece. When epididymal spermatozoa were released into a glucose-containing medium, the NADPH/NADP ratio increased with capacitation. Sperm-oocyte fusion and meiosis reinitiation of the fertilized oocyte was inhibited by the PPP inhibitor 6-aminonicotinamide (6-AN); inhibition of sperm-oocyte fusion was relieved by NADPH. Sperm-oocyte fusion and meiosis reinitiation were also inhibited by diphenylamine iodonium, which is a flavoenzyme inhibitor reported to prevent reactive oxygen species (ROS) generation in mouse spermatozoa and embryos. These findings indicate that the PPP is involved in different steps of fertilization. Subsequent regulation of a NADPH-dependent flavoenzyme responsible of ROS production is envisaged.
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PMID:Involvement of the pentose phosphate pathway and redox regulation in fertilization in the mouse. 1568 28

Alkaline gel electrophoresis, pulsed field gel electrophoresis, and quantitative PCR analyses (QPCR) of the nuclear (nDNA) and mitochondrial (mtDNA) genomes were used to assess DNA integrity in the spermatozoa of three species exposed to oxidative stress. In human and murine spermatozoa, the mtDNA was significantly more susceptible to H2O2-mediated damage than nDNA. In both eutherian species, exposure to 250 microM H2O2 induced around 0.6 lesions/10 kb of mtDNA. The mtDNA of human spermatozoa was particularly vulnerable to oxidative stress; 0.25, 1, and 5 mM H2O2 inducing DNA damage equivalent to 0.62, 1.34, and 1.42 lesions/10 kb, respectively. Such results emphasize the diagnostic significance of mtDNA as a biomarker of oxidative stress in the male germ line. In contrast, no damage could be detected by QPCR in the nDNA of either eutherian species, on exposure to H2O2 at doses as high as 5 mM. However, electrophoretic analysis indicated that severe oxidative stress could induce detectable nDNA fragmentation in human, but not murine spermatozoa. The mtDNA of tammar wallaby spermatozoa was relatively resistant to oxidative stress, only exhibiting damage (0.6 lesions/10 kb DNA) on exposure to 5 mM H2O2. By contrast, the nDNA of wallaby spermatozoa was significantly more susceptible to this oxidant than the other species. Such vulnerability is consistent with the lack of disulfide cross-linking in marsupial sperm chromatin and suggests that chromatin condensation during epididymal maturation may be important in establishing the resistance of these cells to the genotoxic effects of reactive oxygen species.
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PMID:A comparative study of oxidative DNA damage in mammalian spermatozoa. 1573 37

The contraceptive efficacy and toxicological screening of the two principal compounds, MCP I and ECP I, isolated from the seeds of Carica papaya, in male albino rats at the standardized dose regimen, at 50 mg/kg b.w./day, for a period of 360 days and up to 90 days of treatment withdrawal have been reported. The body and organ weights, cauda epididymal sperm characteristics, androgen sensitive tissue biochemistry, reactive oxygen species and anti-oxidant defense system in the cauda epididymal microenvironment, histology and ultrastructure of testis and cauda epididymis, histology of seminal vesicle and prostate, toxicological investigations through routine hematology and serum clinical chemistry, sexual behaviour and fertility index have been studied. The results revealed that oral administration of MCP I and ECP I were equally effective, exhibiting complete inhibition of sperm motility following 90 days of treatment that coincided with a gradual and significant decline in cauda epididymal sperm density, percent viable spermatozoa and significant increase in sperm anomalies. Histology of testis of treated animals revealed degenerated germinal epithelium, vacuolization in Sertoli cells and proliferating germ cells and disturbances in spermatid differentiation. Spermatogonial stem cell reserves and Leydig cells appeared normal. Ultrastructure of the testis revealed vacuolization in the Sertoli cells and germ cells, loss of cytoplasmic characteristics in the Sertoli cells, nuclear degeneration and mitochondrial vacuolization in spermatocytes and spermatids. Leydig cells exhibited steroidogenic features. Cauda epididymis showed normal epithelial cell function. Absence of spermatozoa or disruption of spermatozoa clusters in the lumen were evident. Ultrastructure of cauda epididymis revealed normal secretory activity. Morphology of seminal vesicle and prostate of the treated animals were comparable to control animals. Serum testosterone, tissue biochemical and toxicological parameters remained unaffected. Fertility test revealed 100% efficacy. All the altered parameters showed sign of recovery following 90 days of treatment withdrawal. It is concluded that both MCP I and ECP I are equally effective in terms of contraceptive efficacy which is likely reversible and without adverse side effects.
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PMID:Efficacy trial on the purified compounds of the seeds of Carica papaya for male contraception in albino rat. 1580 97

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant known to exhibit toxic effects on the male reproductive system, including the epididymus and spermatozoa. However, the mechanism(s) that mediate dioxin toxicity in spermatozoa remain unclear. The aim of the present study was to investigate whether exposure to TCDD would cause a loss in mitochondrial membrane potential (Deltapsi(m)) in spermatozoa and whether such an effect is mediated by the Ah receptor (AhR). Exposure of C57BL/6 male mice to TCDD at concentrations of 0.1-50 microg/kg for 24 h caused a dose-dependent loss of Deltapsi(m) in epididymal spermatozoa compared to spermatozoa from vehicle-treated mice. However, this effect was not apparent in spermatozoa from AhR knockout (KO) mice. Exposure of spermatozoa from C57BL/6 mice to 1 nM or 5 nM TCDD in vitro also induced loss of Deltapsi(m). TCDD-exposed C57BL/6 mice failed to exhibit changes in the morphology of testes and epididymus, and did not show any increase in number of apoptotic germ cells. In addition, comparison of reactive oxygen species (ROS) production in spermatozoa from vehicle- and TCDD-treated mice indicated that exposure to TCDD resulted in elevated ROS levels in the spermatozoa from TCDD-treated mice. Moreover, blockade of ROS production by pretreatment with ROS scavenger N-acetylcysteine (NAC) mitigated the loss of Deltapsi(m) following TCDD exposure. Taken together, these data suggest that direct exposure of spermatozoa to TCDD triggers loss of Deltapsi(m) that is mediated by AhR-dependent production of ROS.
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PMID:Aryl hydrocarbon receptor-dependent induction of loss of mitochondrial membrane potential in epididydimal spermatozoa by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). 1583 97

Oxidative stress has been shown to be a major cause of male infertility; a large proportion of infertile men have elevated levels of seminal reactive oxygen species (ROS). High concentrations of ROS cause sperm pathology such as ATP depletion leading to insufficient axonemal phosphorylation, lipid peroxidation and loss of motility and viability. L-carnitine, a naturally occurring enzymatic antioxidant, is a necessary factor in the utilization of long chain fatty acids to produce energy. Furthermore, it plays a pivotal role in the maturation of spermatozoa within the male reproductive tract. Epididymal plasma contains the highest levels of L-carnitine found in the human body, and initiation of sperm motility occurs in parallel to L-carnitine increase in the epididymal lumen. It is known that L-carnitine prevents the formation of ROS, scavenges free radicals and protects cells from peroxidative stress. Moreover, it plays a key role in sperm metabolism by providing readily available energy for use by spermatozoa, which positively affects sperm motility, maturation and the spermatogenic process. L-carnitine and its derivatives have been proposed recently for treatment of male infertility, and a number of controlled and uncontrolled human and animal studies have been conducted to indicate their possible application. As a result, antioxidant therapy with carnitines may represent a new nonhormonal option within a broader therapeutic strategy in men with ROS-mediated infertility.
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PMID:Oxidative stress, male infertility and the role of carnitines. 1615 68

Oxidative damage is one threat spermatozoa have to face during epididymal maturation and storage. However, it is clear that reactive oxygen species (ROS) are also central for sperm physiology in processes such as sperm maturation and capacitation. It is therefore essential that there exists around sperm cells a fine balance between ROS production and recycling. To do so, sperm cells and epididymal epithelial cells rely on common enzymatic ROS scavengers such as superoxide dismutase (SOD), glutathione peroxidases (GPX) and catalase (CAT) as well as more specific types such as indoleamine dioxygenase (IDO). Among the catalytic triad (SOD/GPX/CAT), the glutathione peroxidase protein family occupies a peculiar position, since several GPX have been found to be present on and around epididymal transiting sperm cells. Here, we will review our present knowledge regarding GPX expression, presence and putative role(s) within the epididymis and on spermatozoa. Taking into account our recent findings regarding the epididymal expression of indoleamine dioxygenase in mouse we will also discuss how we think this superoxide anion recycling enzyme completes the complex ROS generation/recycling balance in this organ.
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PMID:The antioxidant glutathione peroxidase family and spermatozoa: a complex story. 1642 83

The present study describes the extent and pattern of oxidative stress induction in testis and epididymal sperm of rats following in vivo exposure to repeated sublethal doses of 2 model pro-oxidants, namely, t-butyl hydroperoxide (tbHP) and cumene hydroperoxide (cHP). Single sublethal (1/40, 1/20, and 1/10 LD(50)) doses of hydroperoxides (HP) administered intraperitoneally to male rats (CFT-Wistar strain) failed to induce any significant increase in malondialdehyde or reactive oxygen species (ROS) levels in testis or epididymal sperm. However, repeated doses for 1 or 2 weeks induced a marked dose-related enhancement of lipid peroxidation (LPO) and ROS levels in both testis and epididymal sperm. Further evidence, such as significant perturbations in both enzymic and nonenzymic antioxidants and enhanced levels of protein carbonyls in testis, suggested induction of oxidative stress. In testis, moderate depletion in reduced glutathione levels and marked diminution in ascorbic acid and alpha-tocopherol content were accompanied by increased activities of various antioxidant enzymes, namely glutathione peroxidase, glutathione-S-transferase, and catalase, in both the HP treatments. Furthermore, significant alterations in the specific activities of testicular enzymes such as LDH-X, G-6-PDH, and SDH indicated altered testicular physiology. Both HP at higher doses induced significant DNA damage (determined by fluorimetric analysis of DNA unwinding assay) in testis and epididymal sperm. Increased total iron levels in testis of HP-treated rats are indicative of the possible involvement of iron-mediated free radical reactions in this model. These findings provide an account of early oxidative damage in testis and epididymal sperm following short-term exposure to HP in vivo, and this model is being further exploited for understanding the consequences of chronic oxidative stress-mediated alterations for the physiology of male reproductive system and its implications for fertility.
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PMID:Induction of oxidative stress by organic hydroperoxides in testis and epididymal sperm of rats in vivo. 1692 93

As the proportion of aged males attempting to reproduce continues to rise, so does the concern regarding the quality of spermatozoa from aged men. An imbalance between the generation of reactive oxygen species (ROS) and cellular antioxidant defenses, as occurs in aging, ultimately leads to decreased protein, lipid, and DNA quality. Spermatozoa are highly susceptible to oxidative damage, and thus an age-related shift in redox status may have serious implications for fertility. Therefore, we examined the effect of age on antioxidant enzymatic activity, ROS production, and extent of lipid peroxidation in both caput and cauda epididymal spermatozoa from young (4-month-old) and old (21-month-old) Brown Norway rats. Glutathione peroxidase (Gpx1, Gpx4) and superoxide dismutase (SOD) enzymes had decreased activity in aging spermatozoa. Immunofluorescence studies indicated that Gpx4 expression was decreased in both the head and midpiece regions of spermatozoa in aged animals. The decrease in nuclear Gpx4 points to a novel potential mechanism that may explain the previously noted decreased levels of protamine disulfide bonds in aged sperm nuclei. Further, hydrogen peroxide (H2O2) and superoxide (O2(.-)) production were increased significantly in aging spermatozoa. Finally, lipid peroxidation was found to be drastically increased in aged spermatozoa. Taken together, these results suggest a decreased capacity for aged spermatozoa to handle oxidative stress and provide a potential basis for understanding the underlying cause of decreased quality of spermatozoa during aging.
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PMID:Spermatozoa have decreased antioxidant enzymatic capacity and increased reactive oxygen species production during aging in the Brown Norway rat. 1702 40


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