Reactive oxygen species as mediators of sperm capacitation and pathological damage.

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Reactive oxygen species as mediators of sperm capacitation and pathological damage.

Mol Reprod Dev. 2017 Jul 27;:

Authors: Aitken RJ

Abstract
Oxidative stress plays a major role in the life and death of mammalian spermatozoa. These gametes are professional generators of reactive oxygen species (ROS), which appear to derive from three potential sources: sperm mitochondria, cytosolic L-amino acid oxidases, and plasma membrane nicotinamide adenine dinucleotide phosphate oxidases. The oxidative stress created via these sources appears to play a significant role in driving the physiological changes associated with sperm capacitation through the stimulation of a cyclic adenosine monophosphate/Protein kinase A phosphorylation cascade, including the activation of Extracellular signal regulated kinase-like proteins, massive up-regulation of tyrosine phosphorylation in the sperm tail, as well as the induction of sterol oxidation. When generated in excess, however, ROS can induce lipid peroxidation that, in turn, disrupts membrane characteristics that are critical for the maintenance of sperm function, including the capacity to fertilize an egg. Furthermore, the lipid aldehydes generated as a consequence of lipid peroxidation bind to proteins in the mitochondrial electron transport chain, triggering yet more ROS generation in a self-perpetuating cycle. The high levels of oxidative stress created as a result of this process ultimately damage the DNA in the sperm nucleus; indeed, DNA damage in the male germ line appears to be predominantly induced oxidatively, reflecting the vulnerability of these cells to such stress. Extensive evaluation of antioxidants that protect the spermatozoa against oxidative stress while permitting the normal reduction-oxidation regulation of sperm capacitation is therefore currently being undertaken, and has already proven efficacious in animal models. This article is protected by copyright. All rights reserved.

PMID: 28749007 [PubMed – as supplied by publisher]

Protective effects of melatonin on bovine sperm characteristics and subsequent in vitro embryo development.

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Protective effects of melatonin on bovine sperm characteristics and subsequent in vitro embryo development.

Mol Reprod Dev. 2016 Sep 21;

Authors: Pang YW, Sun YQ, Jiang XL, Huang ZQ, Zhao SJ, Du WH, Hao HS, Zhao XM, Zhu HB

Abstract
We aimed to investigate the effect of melatonin on bovine frozen-thawed semen and its impact on fertilization outcome. Plasma membrane integrity, mitochondrial activity, acrosome integrity, and levels of intracellular reactive oxygen species (ROS) were measured in spermatozoa treated with different concentrations of melatonin. Melatonin-treated spermatozoa were then used for in vitro fertilization, followed by analysis of subsequent embryo development and the expression of apoptosis- and antioxidant-related genes. The results revealed that 10(-5) and 10(-3)  M melatonin led to higher plasma membrane integrity, mitochondrial activity, and acrosome integrity, and significantly decreased intracellular ROS levels (P < 0.05). The blastocyst development rate of in vitro-produced bovine embryos originating from 10(-3)  M melatonin-treated spermatozoa was significantly higher, while the incidence of apoptotic nuclei in blastocysts was markedly lower than for embryos from any other group (P < 0.05). CASP3 and BAX mRNA abundances were significantly down-regulated whereas BCL2, XIAP, and CAT transcript abundance was significantly increased in embryos produced from spermatozoa treated with 10(-3)  M melatonin; GPX4 expression, however, was comparable in all treatment groups. Thus, 10(-3)  M melatonin can improve the quality of bovine frozen-thawed semen. These beneficial effects appear to influence preimplantation embryos, given the correlation with its anti-apoptotic and anti-oxidative properties. This article is protected by copyright. All rights reserved.

PMID: 27653174 [PubMed – as supplied by publisher]

Alpha-lipoic acid and N-acetylcysteine protects intensive swimming exercise-mediated germ-cell depletion, pro-oxidant generation, and alteration of steroidogenesis in rat testis.

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Alpha-lipoic acid and N-acetylcysteine protects intensive swimming exercise-mediated germ-cell depletion, pro-oxidant generation, and alteration of steroidogenesis in rat testis.

Mol Reprod Dev. 2014 Aug 7;

Authors: Jana K, Dutta A, Chakraborty P, Manna I, Firdaus SB, Bandyopadhyay D, Chattopadhyay R, Chakravarty B

Abstract
Prolonged and strenuous exercise has been proposed as a possible source of male-factor infertility. Forced intensive swimming has also been identified as one source of a dysfunctional male reproduction system. The present study evaluated the possible protective role of α-lipoic acid and N-acetylcysteine (NAC) on intensive swimming-induced germ-cell depletion in adult male rats. Forced exhaustive swimming of 1 hr/day, 6 days/week for 8 consecutive weeks resulted in a significant (P < 0.05) reduction in epididymal sperm; testicular androgenic enzyme activities; and plasma and intra-testicular testosterone; and produced different types of germ cells in the seminiferous epithelium cycle. Conversely, plasma corticosterone levels and sperm-head abnormalities increased. Western-blot analysis showed a considerable decrease in testicular StAR protein expression whereas reverse-transcriptase PCR analysis showed no significant change in cytochrome P450scc (Cyp11a1) gene expression. Significant (P < 0.05) elevation in testicular reactive oxygen species (ROS), lipid peroxidation, protein carbonyl content versus reduction in glucose-6-phosphate dehydrogenase, glutathione peroxidase, glutathione S-transferase, and caspase-3 activities along with a depletion in the glutathione pool, mitochondrial membrane potential (▵ψm ), and intracellular ATP generation. A considerable level of DNA damage in testicular spermatogenic cells were also noted following forced extensive swimming. Alpha-lipoic acid and NAC supplementation prevented the swimming-induced testicular spermatogenic and steroidogenic disorders by lowering ROS generation. We therefore conclude that intensive forced swimming causes germ-cell depletion through the generation of ROS and depletion of steroidogenesis in the testis, which can be protected by the co-administration of α-lipoic acid and NAC. Mol. Reprod. Dev. 2014. © 2014 Wiley Periodicals, Inc.

PMID: 25104294 [PubMed – as supplied by publisher]

Chromosomal aberrations, Yq microdeletion, and sperm DNA fragmentation in infertile men opting for assisted reproduction.

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Chromosomal aberrations, Yq microdeletion, and sperm DNA fragmentation in infertile men opting for assisted reproduction.

Mol Reprod Dev. 2012 Jul 9;

Authors: Shamsi MB, Kumar R, Malhotra N, Singh N, Mittal S, Upadhyay AD, Dada R

Abstract
Male infertility is a multi-factorial disorder, and identification of its etiology in an individual is critical for treatment. Systematically elucidating the underlying genetic causes (chromosomal and Yq microdeletion) and factors, such as reactive oxygen species (ROS) levels and total antioxidant capacity (TAC), which both contribute to sperm DNA damage, may help to reduce the number of men with idiopathic infertility and provide them most suitable therapeutics and counseling. This study was done to comprehensively investigate genetic and oxidative stress factors that might be the etiology of a large percentage of men with idiopathic infertility. One hundred and twelve infertile men and seventy-six fertile controls were screened for chromosomal aberrations and Yq microdeletions. ROS, TAC, and sperm DNA damage were assessed in cytogenetically normal, non-azoospermic men with intact Y chromosome (n = 93). ROS was assessed in neat and washed semen by chemiluminescense; seminal TAC with a commercially available kit; and sperm DNA damage by the comet assay. Two men had cytogenetic abnormalities and 7 men harboured Yq microdeletions. ROS levels in neat and washed semen of infertile men were significantly higher (p < 0.01) than controls. Infertile men had significantly lower (p< 0.01) TAC levels (1.79 mM), whereas sperm DNA fragmentation in infertile men was significantly higher (p < 0.01) than controls. Genetic factors and oxidative stress cumulatively account for large number of idiopathic infertile cases. Unlike, genetic causes, which cannot be cured, timely identification and management of oxidative stress may help to reverse/reduce the effects on induced DNA damage, and improve the outcomes for infertile males. Mol. Reprod. Dev. © 2012 Wiley Periodicals, Inc.

PMID: 22777732 [PubMed – as supplied by publisher]

Ethanol induces mouse spermatogenic cell apoptosis in vivo through over-expression of Fas/Fas-L, p53, and caspase-3 along with cytochrome c translocation and glutathione depletion.

Ethanol induces mouse spermatogenic cell apoptosis in vivo through over-expression of Fas/Fas-L, p53, and caspase-3 along with cytochrome c translocation and glutathione depletion.

Mol Reprod Dev. 2010 Sep;77(9):820-33

Authors: Jana K, Jana N, De DK, Guha SK

Although it has been well established that spermatogenic cells undergo apoptosis when treated with ethanol, the molecular mechanisms behind it remain to be investigated. Adult male mice were given intra-peritoneal injection (IP) of ethanol at a dose of 3 g (15%, v/v) per kg body weight per day during the period of 14 days. Testicular androgenesis and apoptotic germ cell death, along with different interrelated proteins expression, were evaluated. Ethanol treatment induced apoptotic spermatogenic cell death with a decrease in the plasma and intra-testicular testosterone concentration. Western blot analysis revealed that repeated ethanol treatment decreased the expression of steroidogenic acute regulatory protein (StAR), 3 beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17 beta-hydroxysteroid dehydrogenase (17beta-HSD); increased the expression of active caspase-3, p53, Fas and Fas-L; and led to up-regulation of Bax/Bcl-2 ratio and translocation of cytochrome c from mitochondria to cytosol in testis. It has also been shown in our study that repeated ethanol treatment led to up-regulation of caspase-3, p53, Fas, Fas-L transcripts; increase in caspase-3 and caspase-8 activities; diminution of 3beta-HSD, 17beta-HSD, and GPx activities; decrease in the mitochondrial membrane potential along with ROS generation and depletion of glutathione pool in the testicular tissue. The present study has indicated that the ethanol treatment induced apoptosis in the mouse testis through the increased expression of Fas/Fas-L and p53, up-regulation of Bax/Bcl-2 ratio, cytosolic translocation of cytochrome c along with caspase-3 activation and glutathione depletion.

PMID: 20803734 [PubMed – indexed for MEDLINE]