scholarly journals Oxidative stress, DNA damage and the Y chromosome

Reproduction ◽  
2001 ◽  
pp. 497-506 ◽  
Author(s):  
RJ Aitken ◽  
C Krausz
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Y Chromosome ◽  
Nuclear Dna ◽  
Germ Line ◽  
Reactive Oxygen Species Generation ◽  
High Rate ◽  
Severe Oligozoospermia ◽  
Gene Deletions ◽  
Chromosome Deletions

Recent advances in understanding of male infertility have implicated two major causative factors, oxidative stress and Y chromosome deletions. A major cause of oxidative stress appears to be the high rate of reactive oxygen species generation associated with the retention of excess residual cytoplasm in the sperm midpiece. Other possible causes include the redox cycling of xenobiotics, and antioxidant depletion or apoptosis. Oxidative stress induces peroxidative damage in the sperm plasma membrane and DNA damage in both the mitochondrial and nuclear genomes. Nuclear DNA damage in the germ line of the father may be associated with pathology in the offspring, including childhood cancer and infertility. Gene deletions on the non-recombining region of the Y chromosome account for the infertility observed in about 15% of patients with azoospermia and 5-10% of subjects with severe oligozoospermia. The Y chromosome is particularly susceptible to gene deletions because of the inability of the haploid genome to deploy recombination repair in retrieving lost genetic information. Aberrant recombination, defective chromatin packaging, abortive apoptosis and oxidative stress may all be involved in the aetiology of DNA damage in the germ line. The factors responsible for Y chromosome deletions in spermatozoa remain unresolved but may be one facet of a central reproductive problem: controlling the amount of oxidative stress experienced by germ cells during their differentiation and maturation in the male reproductive tract.

scholarly journals Oxidative stress, DNA damage and the Y chromosome

Reproduction ◽  
2001 ◽  
Vol 122 (4) ◽  
pp. 497-506 ◽  
Author(s):  
R. Aitken
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Y Chromosome

Oxidative stress and nuclear DNA damage in hyperglycemic pregnancies

Placenta ◽  
2015 ◽  
Vol 36 (4) ◽  
pp. 505
Author(s):  
J.B. Moreli ◽  
J.H. Santos ◽  
R.S. Fortunato ◽  
S. Corrêa-Silva ◽  
D.C. Damasceno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Nuclear Dna

scholarly journals Simultaneous Quantification of Mitochondrial DNA Damage and Copy Number in Circulating Blood: A Sensitive Approach to Systemic Oxidative Stress

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Sam W. Chan ◽  
Simone Chevalier ◽  
Armen Aprikian ◽  
Junjian Z. Chen
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Mitochondrial Dna ◽  
Copy Number ◽  
Structural Damage ◽  
Oxidative Dna Damage ◽  
Nuclear Dna ◽  
Blood Analysis ◽  
Systemic Oxidative Stress ◽  
Wide Range

Systemic oxidative stress is associated with a wide range of pathological conditions. Oxidative DNA damage is frequently measured in circulating lymphocytes. Mitochondrial DNA (mtDNA) is known to be more sensitive to oxidative damage than nuclear DNA but is rarely used for direct measurement of DNA damage in clinical studies. Based on the supercoiling-sensitive real-time PCR method, we propose a new approach for the noninvasive monitoring of systemic oxidative stress by quantifying the mtDNA structural damage and copy number change in isolated lymphocytes in a single test. We show that lymphocytes have significantly less mtDNA content and relatively lower baseline levels of damage than cancer cell lines. In anex vivochallenge experiment, we demonstrate, for the first time, that exogenous H2O2induces a significant increase in mtDNA damage in lymphocytes from healthy individuals, but no repair activity is observed after 1 h recovery. We further demonstrate that whole blood may serve as a convenient alternative to the isolated lymphocytes in mtDNA analysis. Thus, the blood analysis with the multiple mtDNA end-points proposed in the current study may provide a simple and sensitive test to interrogate the nature and extent of systemic oxidative stress for a broad spectrum of clinical investigations.

scholarly journals 002.Human spermatozoa: fruits of creation, seed of doubt

2004 ◽  
Vol 16 (9) ◽  
pp. 2
Author(s):  
R. J. Aitken
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Dna Repair ◽  
Germ Cells ◽  
Oxidative Dna Damage ◽  
Germ Line ◽  
Early Embryo ◽  
Human Spermatozoa ◽  
Obstructive Azoospermia ◽  
Male Germ Line

Defective sperm function is the largest defined cause of human infertility, affecting one in twenty Australian males. Despite its prevalence, we are only just beginning to understand the underlying mechanisms. The past decade has seen two major advances in this field: (1) the discovery that Y chromosome deletions play a key role in the aetiology of non-obstructive azoospermia/oligozoospermia; and (2) recognition that oxidative stress can impact upon the functional competence of human spermatozoa through peroxidative damage to the sperm plasma membrane. Oxidative stress has also been found to disrupt the integrity of DNA in the male germ line and may represent an important mechanism by which environmental impacts on human health are mediated. Thus, paternal exposure to various toxicants (cigarette smoke, organic solvents, heavy metals) has been linked with oxidative DNA damage in spermatozoa and developmental defects, including cancer, in the F1 generation. The male germ line becomes particularly vulnerable to such factors during the post meiotic stages of differentiation. Pre-meiotic germ cells always have the option of undergoing apoptosis if DNA damage is severe. However, post meiotic germ cells have lost both the ability to mount an apoptotic response and the capacity for DNA repair. As a result, germ cells are particularly vulnerable to genotoxic agents during spermiogenesis and epididymal maturation. If the fertilizing capacity of the spermatozoa is retained following toxicant exposure, then DNA damage will be transferred to the zygote and must be repaired subsequently by the oocyte and/or early embryo. Aberrant DNA repair at this stage has the potential to create mutations that will compromise embryonic development and, ultimately, the normality of the offspring. Elucidating the causes of oxidative damage in spermatozoa should help resolve the aetiology of conditions such as male infertility, early pregnancy loss and childhood disease, including cancer.

scholarly journals The senescence-accelerated mouse prone 8 as a model for oxidative stress and impaired DNA repair in the male germ line

Reproduction ◽  
2013 ◽  
Vol 146 (3) ◽  
pp. 253-262 ◽  
Author(s):  
T B Smith ◽  
G N De Iuliis ◽  
T Lord ◽  
R J Aitken
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Dna Repair ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Reactive Oxygen Species Generation ◽  
Control Strain ◽  
Base Excision ◽  
High Level ◽  
Senescence Accelerated Mouse

The discovery of a truncated base excision repair pathway in human spermatozoa mediated by OGG1 has raised questions regarding the effect of mutations in critical DNA repair genes on the integrity of the paternal genome. The senescence-accelerated mouse prone 8 (SAMP8) is a mouse model containing a suite of naturally occurring mutations resulting in an accelerated senescence phenotype largely mediated by oxidative stress, which is further enhanced by a mutation in theOgg1gene, greatly reducing the ability of the enzyme to excise 8-hydroxy,2′-deoxyguanosine (8OHdG) adducts. An analysis of the reproductive phenotype of the SAMP8 males revealed a high level of DNA damage in caudal epididymal spermatozoa as measured by the alkaline Comet assay. Furthermore, these lesions were confirmed to be oxidative in nature, as demonstrated by significant increases in 8OHdG adduct formation in the SAMP8 testicular tissue (P<0.05) as well as in mature spermatozoa (P<0.001) relative to a control strain (SAMR1). Despite this high level of oxidative DNA damage in spermatozoa, reactive oxygen species generation was not elevated and motility of spermatozoa was found to be similar to that for the control strain with the exception of progressive motility, which exhibited a slight but significant decline with advancing age (P<0.05). When challenged with Fenton reagents (H2O2and Fe2+), the SAMP8 spermatozoa demonstrated a highly increased susceptibility to formation of 8OHdG adducts compared with the controls (P<0.001). These data highlight the role of oxidative stress and OGG1-dependent base excision repair mechanisms in defining the genetic integrity of mammalian spermatozoa.

248. Oxidative stress and DNA damage in human spermatozoa

2008 ◽  
Vol 20 (9) ◽  
pp. 48
Author(s):  
G. N. De Iuliis ◽  
J. M. Finnie ◽  
R. J. Aitken
Keyword(s):  
Oxidative Stress ◽  
Mass Spectrometry ◽  
Dna Damage ◽  
Metal Ions ◽  
Electromagnetic Radiation ◽  
Germ Line ◽  
Human Spermatozoa ◽  
Ros Production ◽  
Male Germ Line ◽  
Catechol Estrogens

Unusually high levels of DNA damage in the male germ line are, unfortunately, characteristic of our species. A great deal of circumstantial evidence has linked DNA damage in human spermatozoa with adverse reproductive outcomes including reduced fertility and high rates of miscarriage. Although oxidative stress is thought to make a significant contribution to DNA damage in the male germ line, the mechanisms responsible for creating this stress have not yet been elucidated. We have undertaken a detailed analysis of the ability of estrogens, electromagnetic radiation and xenobiotics including metal ions to trigger reactive oxygen species (ROS) production and/or DNA damage in human spermatozoa in vitro. This investigation was completed using a range of techniques validated for use in these highly specialised cells. DNA integrity was assessed using the Comet and TUNEL assays, oxidative DNA adducts were detected by an anti-8-oxo-dG assay and cross-linking adducts were characterised by mass spectrometry. Intracellular redox activity was monitored using dihydroethidium as the probe. Of the factors evaluated, catechol estrogens, certain transition metal ions, radio frequency electromagnetic radiation and heat were all capable of stimulating ROS production in human spermatozoa. The oxidative stress created by exposure to such factors lead to the induction of significant DNA damage. Generally, redox inert compounds including non-catechol estrogens and xenobiotics such as phthalate esters did not lead to ROS production or measurable DNA damage. Mass spectrometry also indicated that catechol estrogens were capable of forming dimers that can cross-link the densely packed DNA strands in sperm chromatin. These findings raise fundamental questions about the importance of xenobiotics, environmental factors as well endogenous compounds in creating oxidative stress and DNA damage in the male germ line.

Effect of nucleotide supplementation on lymphocyte DNA damage induced by dietary oxidative stress in pigs

2005 ◽  
Vol 81 (1) ◽  
pp. 135-140 ◽  
Author(s):  
J. Salobir ◽  
V. Rezar ◽  
T. Pajk ◽  
A. Levart
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Glutathione Peroxidase ◽  
Nuclear Dna ◽  
Linseed Oil ◽  
Basal Diet ◽  
Growing Pigs ◽  
Adaptation Period ◽  
Anti Oxidant ◽  
Oxidant Status

AbstractThe aim of the present study was to evaluate the effect of nucleotide supplementation on the oxidative stress induced by a high proportion of dietary polyunsaturated fatty acids ( PUFAs) in pigs. Twenty-four male growing pigs were penned individually and after an adaptation period divided into three groups. All groups received isocaloric daily rations composed of a basal diet supplemented with either: starch (CONT), linseed oil (LIN) and LIN and nucleotides (LIN + NUC). The experimental period lasted 21 days. Oxidative stress was evaluated by measuring the degree of lymphocyte nuclear DNA damage, the urine malondialdehyde ( MDA) excretion rate, erythrocyte glutathione peroxidase concentration and the total anti-oxidant status of plasma. Malondialdehyde concentrations in the blood and MDA urinary excretion rates were higher (P< 0·01) in animals supplemented with LIN and LIN + NUC compared with CONT animals. The degree of DNA damage in the LIN-supplemented animals was also higher (P< 0·01). Compared with the LIN-supplemented animals, nucleotide supplementation reduced (P< 0·01) the degree of DNA damage in lymphocytes to the level of the CONT group. Erythrocyte glutathione peroxidase concentration and plasma total anti-oxidant status were similar across treatments. The results of this experiment indicate that nucleotide supplementation effectively eliminates the genotoxic effects of high PUFA intakes on blood lymphocytes and demonstrates new evidence for the immunonutritive effect of nucleotides.

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