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Download references. Department of Anatomy, Laboratory for Molecular Reproduction and Genetics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, , India.

You can also search for this author in PubMed Google Scholar. Correspondence to Rima Dada. A free radical is an atom or molecule that is highly reactive because it contains an unpaired electron in the outer shell.

A process that sperm undergo as they travel through the woman's reproductive tract. Capacitation enables the sperm to penetrate the egg. Results from an imbalance between the intracellular production of free radicals and the cellular defence mechanisms.

Any substance that prevents or reduces damage caused by free-radicals highly reactive chemicals containing oxygen that attack other molecules and modify their chemical structure.

Splitting of DNA strands into shorter pieces by endonucleolytic DNA cleavage at multiple sites. This process includes internucleosomal DNA fragmentation, which, along with chromatin condensation, is considered a hallmark of apoptosis. All treatments or procedures that include the in vitro handling of both human oocytes and sperm or of embryos for the purpose of establishing a pregnancy.

A practice of concentrated focus upon a sound, object, visualization, such as the breath, movement, or attention itself in order to increase awareness of the present moment, reduce stress, promote relaxation, and enhance personal and spiritual growth. A Hindu spiritual and ascetic discipline, a part of which, including breath control, simple meditation, and the adoption of specific bodily postures, is widely practiced for health and relaxation purposes.

Proteins that bind with DNA in sperm cells, replacing histones and allowing chromosomes to become more highly condensed than is possible with histones. A telomere is a region of repetitive nucleotide sequences at each end of a chromosome, which protect the end of the chromosome from deterioration or from fusion with neighbouring chromosomes.

Telomere length decreases with advancing cellular age, thus strategies that reduce the rate of telomere shortening might delay the cellular ageing process.

Semen containing no sperm, either because the testicles cannot produce sperm or because of a blockage in the reproductive tract. A testicular cell responsible for nurturing the spermatids immature sperm.

These cells secrete inhibin, a hormone that regulates follicule-stimulating hormone FSH production by the pituitary gland. When stimulated by FSH, the Sertoli cell initiates spermatogenesis.

The active maintenance of all the genetic elements in the cells of an organism including DNA, RNA and epigenetic determinants and appropriate developmental gene expression for proper dynamic function. Reprints and permissions. Bisht, S. Oxidative stress and male infertility. Nat Rev Urol 14 , — Download citation.

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Skip to main content Thank you for visiting nature. nature nature reviews urology review articles article. Subjects DNA damage and repair Lifestyle modification Male factor infertility Stress signalling. Abstract DNA damage, largely owing to oxidative stress, is a leading cause of defective sperm function.

Access through your institution. Buy or subscribe. Change institution. Learn more. Figure 1: Causes and consequences of seminal oxidative stress and oxidative DNA damage. References Rowe, P.

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Article PubMed PubMed Central Google Scholar Twigg, J. Article CAS PubMed Google Scholar Nakamura, H. Article CAS PubMed Google Scholar Darzynkiewicz, Z. At least 25 studies report various combinations in different populations of infertile men but only a dozen use a measure of sperm oxidative stress Table I.

Vitamin E, a well-known lipophilic antioxidant has been most widely used in combination with a variety of hydrophilic antioxidants such as vitamin C, selenium and zinc in addition to other miscellaneous combinations.

Somewhat surprisingly, the results from the 12 combination studies mirror those observed with single antioxidants with no apparent synergistic effects on any of the outcome variables. Although, 11 of the 12 studies confirmed a significant reduction of sperm oxidtive stress or DNA damage, only 5 of the 10 studies that measured motility showed improvement.

None of the studies showed any significant improvement in morphology and only 2 of 10 studies showed an improvement in sperm concentration. In summary, to date, almost every study that has measured the effect of antioxidants on sperm oxidative stress or DNA damage indicates a significant improvement.

Additionally, the effect of antioxidants on motility appears to be compelling, particularly in asthenospermic patients. Such improvements in sperm motility are clinically and biologically important given the wealth of data linking the movement characteristics of human spermatozoa with the fertilizing potential of these cells in vivo and in vitro Aitken, However, the results of the 20 studies summarized in Table I do not differentiate an appreciable advantage for lipophilic versus hydrophilic antioxidants nor reveal any additive or synergistic effects when combined together.

However, it should be emphasized that a majority of these studies were small, heterogeneous and did not generate sufficient data to confirm whether the improvements gained by antioxidant therapy result in improved secondary outcomes.

Thus, the quest to identify novel antioxidants and combinations that are optimized for safety and efficacy is likely to continue. On theoretical grounds, an appropriate combination of antioxidants should be more effective than any single antioxidant since oxidative stress is a non-localized heterogeneous phenomenon.

For example, vitamin C, carnitines, zinc and NAC are all highly hydrophilic molecules; conversely, vitamin E and carotenoids such as astaxanthin are highly lipophilic structures.

Each of these naturally occurring antioxidants with their own unique pharmacodynamic profile for the male reproductive tract is likely to neutralize at least some of the nearby ROS, thus collectively transpiring to a more effective management of sperm oxidative stress.

However, with a wide selection of antioxidants to choose from, designing an optimum combination will be a challenge.

In developing optimized combinations, particular attention should be paid to the doses and number of ingredients used. Large doses of antioxidants should be avoided due to specific reactions resulting in possible negative effects.

For example, high doses of vitamin C is reported to reduce the interchain disulphide bridges in protamines opening the cysteine net and subsequently promoting DNA decondensation in spermatozoa Donnelly et al.

Selenium at higher doses significantly reduces the number of motile spermatozoa in fertile men possibly through modifying thyroid hormone metabolism Hawkes and Turek, Sperm oxidative stress and DNA damage affect male fertility and may impact upon normal embryo development.

Patients with high levels of sperm DNA damage undergoing ART treatment are at a greater risk of fertilization failure, pregnancy loss or not achieving a healthy progeny.

These risks escalate further if the oocyte's DNA repair mechanisms are compromised. Under the current status quo, sperm DNA damage remains largely undiagnosed and untreated even though one in three men attending IVF clinics exhibit severely elevated levels. From our review of the evidence in 20 clinical studies, there is little doubt over the effectiveness of oral antioxidants to reduce sperm oxidative stress and increase motility in asthenospermic patients, but it is as yet unclear whether this improvement translates to higher full-term pregnancy rates.

It is therefore imperative that future clinical trials with antioxidants target patients with moderate to severe sperm oxidative stress and demonstrate improvement in as many measurable secondary outcomes as possible but, more critically, pregnancy and miscarriage rates.

The trials should be large, carefully designed, if possible multi-centred, double-blind, randomized, crossover with strict selection criteria applied to both genders. conceived and drafted the article, which was then edited and revised by R.

Both authors approved the final version of this article. is the Managing Director of CellOxess LLC, which has a commercial interest in the detection and resolution of oxidative stress.

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Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. An overview of sperm oxidative stress and DNA damage in male infertility.

Diagnosis of sperm oxidative stress and DNA fragmentation: association with clinical outcome. Pharmacological management of sperm oxidative stress with natural antioxidants. Summary and conclusion. Conflict of interest. Journal Article. The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy.

E-mail: p arviz. gharagozloo celloxess. Oxford Academic. John Aitken. Revision received:. PDF Split View Views. Cite Cite Parviz Gharagozloo, R. Select Format Select format. ris Mendeley, Papers, Zotero. enw EndNote. bibtex BibTex. txt Medlars, RefWorks Download citation.

Permissions Icon Permissions. Close Navbar Search Filter Human Reproduction This issue ESHRE Journals Reproductive Medicine Books Journals Oxford Academic Enter search term Search. Abstract Oxidative stress in the male germ line is thought to affect male fertility and impact upon normal embryonic development.

human spermatozoa , reactive oxygen species , oxidative stress , antioxidant therapy. Figure 1. Open in new tab Download slide. Figure 2. Examples of endogenous reactive molecular species often referred to as ROS.

Table I Study characteristics and the effect of oral antioxidants on semen parameters and 2° outcomes. Target patient. Active n. Placb n.

rate Open in new tab. Google Scholar Crossref. Search ADS. Clinical relevance of oxidative stress in male factor infertility: an update. Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa.

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Reactive oxygen species and protein kinases modulate the level of phospho-MEK-like proteins during human sperm capacitation. Evaluating human sperm DNA integrity: relationship between 8-hydroxydeoxyguanosine quantification and the sperm chromatin structure assay.

Treatment of asthenozoospermia with zinc sulphate: andrological, immunological and obstetric outcome. Indications of the mechanisms involved in improved sperm parameters by zinc therapy.

The effects of age on DNA fragmentation, chromatin packaging and conventional semen parameters in spermatozoa of oligoasthenoteratozoospermic patients. Practice Committee of American Society for Reproductive Medicine.

Google Scholar Google Preview OpenURL Placeholder Text. A systematic review of the effect of oral antioxidants on male infertility. Abnormal spermatozoa in the ejaculate: abortive apoptosis and faulty nuclear remodelling during spermatogenesis.

Simultaneous determination in situ of DNA fragmentation and 8-oxoguanine in human sperm. Analysis of gene-specific DNA damage and single-strand DNA breaks induced by pro-oxidant treatment of human spermatozoa in vitro.

Initial observation on L-carnitine for asthenospermia with epididymal knob. Evaluation of oxidative DNA damage in human sperm and its association with male infertility.

Carnitine for the treatment of idiopathic asthenospermia: a randomized, double-blind, placebo-controlled trial. Relationship between seminal ascorbic acid and sperm DNA integrity in infertile men. Sperm integrity pre- and post-chemotherapy in men with testicular germ cell cancer.

Predicting the fertilizing potential of human sperm suspensions in vitro : Importance of sperm morphology and leukocyte contamination.

Lipid peroxidation and human sperm motility: protective role of vitamin E. Detection of deoxyribonucleic acid fragmentation in human sperm: correlation with fertilization in vitro.

Myeloperoxidase-dependent effect of amines on functions of isolated neutrophils. Effect of zinc administration on seminal zinc and fertility of oligospermic males. A randomised control trial examining the effect of an antioxidant Menevit on pregnancy outcome during IVF-ICSI treatment.

Oxidative damage to DNA in human spermatozoa does not preclude pronucleus formation at intracytoplasmic sperm injection. Effects of treatment with carnitines in infertile patients with prostato-vesiculo-epididymitis.

Antioxidant treatment with carnitines is effective in infertile patients with prostatovesiculoepididymitis and elevated seminal leukocyte concentrations after treatment with nonsteroidal anti-inflammatory compounds.

Initiation of rapid, Pdependent growth arrest in cultured human skin fibroblasts by reactive chlorine species. Influence of reactive oxygen species produced by activated leukocytes at the level of apoptosis in mature human spermatozoa. Is there an increased risk of congenital malformations after ART?

Results from a prospective French long-term survey of a cohort of children. Carnitine supplementation in human idiopathic asthenospermia: clinical results. Oxidative stress is associated with increased apoptosis leading to spermatozoa DNA damage in patients with male factor infertility.

Comparative reactivities of various biological compounds with myeloperoxidase-hydrogen peroxide-chloride, and similarity of the oxidant to hypochlorite. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial.

Sperm DNA damage: clinical significance in the era of assisted reproduction. Reactive oxygen species in semen of infertile patients: levels of superoxide dismutase- and catalase-like activities in seminal plasma and spermatozoa.

The histone to protamine ratio in human spermatozoa: comparative study of whole and processed semen. Effects of ageing on spermatozoal chromatin and its sensitivity to in vivo and in vitro oxidative challenge in the Brown Norway rat.