Assessment of DNA integrity and morphology of ejaculated spermatozoa from fertile and infertile men before and after cryopreservation

Donnelly, Eilish

doi:10.1093/humrep/16.6.1191

Cited by 228 publications

(163 citation statements)

References 53 publications

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“…The clinical significance of comet assay in correlating the DNA damage with sperm concentration, morphology, mitochondrial function and oocyte peneteration has been documented in previous studies [95][96][97]. In a study by O'Connell [98] it was reported that sperm isolated from semen by density centrifugation for ART have less DNA fragmentation.…”

Section: Clinical Aspects and Relevance Of Dna Integrity Testsmentioning

confidence: 93%

Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility

Shamsi

Imam

Dada

2011

J Assist Reprod Genet

137

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Sperm is not a simple carrier of paternal genetic information but its role extends clearly beyond fertilization. Integrity of sperm genome is an essential pre-requisite for birth of healthy offspring and evaluation of sperm should entail DNA integrity analysis. DNA integrity analysis is a better diagnostic and prognostic marker of sperm reproductive potential. Conventional semen analysis emphasizes on sperm concentration, viability, motility and morphology and has been proven to be a poor indicator of reproductive potential and pregnancy outcome. To overcome the drawbacks associated with conventional semen analysis more useful fertility tests and molecular biomarkers have been explored. Among the different tests which have evolved for assessing the sperm reproductive potential, tests for sperm DNA quality are most promising. Sperm DNA damage has been closely associated with numerous indicators of reproductive health including fertilization, embryo quality, implantation, spontaneous abortion, congenital malformations and childhood diseases. It therefore has great potential as a prognostic test for both in vitro and in vivo conception. This review presents an updated account of tests that have better diagnostic and prognostic implications in the evaluation of sperm DNA damage. The basic principles, outline of methodology, advantage, disadvantage, clinical significance of each technique and implications of these tests have been discussed. The logistics of each test with respect to available resources and equipment in an andrology laboratory, the feasibility of performing these tests in routine diagnostic workup of infertile men and the opportunities and challenges provided by DNA testing in male fertility determination are also presented.

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Section: Clinical Aspects and Relevance Of Dna Integrity Testsmentioning

confidence: 93%

Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility

Shamsi

Imam

Dada

2011

J Assist Reprod Genet

137

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“…Thus, cryostorage is wellknown to be associated with the induction of DNA damage and, again, a majority of this damage seems to be oxidative. 58,59 Similarly, heat exposure will induce free radical generation by the spermatozoa as a consequence of the initiation of apoptotic cascade, and so will exposure to radiofrequency electromagnetic radiation 21 or hydrogen peroxide. 52 All of these conditions are associated with the creation of oxidative stress.…”

Section: Triggers Of Apoptosismentioning

confidence: 99%

Apoptosis and DNA damage in human spermatozoa

Aitken¹,

Koppers²

2010

Asian J Androl

292

179

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DNA damage is frequently encountered in spermatozoa of subfertile males and is correlated with a range of adverse clinical outcomes including impaired fertilization, disrupted preimplantation embryonic development, increased rates of miscarriage and an enhanced risk of disease in the progeny. The etiology of DNA fragmentation in human spermatozoa is closely correlated with the appearance of oxidative base adducts and evidence of impaired spermiogenesis. We hypothesize that oxidative stress impedes spermiogenesis, resulting in the generation of spermatozoa with poorly remodelled chromatin. These defective cells have a tendency to default to an apoptotic pathway associated with motility loss, caspase activation, phosphatidylserine exteriorization and the activation of free radical generation by the mitochondria. The latter induces lipid peroxidation and oxidative DNA damage, which then leads to DNA fragmentation and cell death. The physical architecture of spermatozoa prevents any nucleases activated as a result of this apoptotic process from gaining access to the nuclear DNA and inducing its fragmentation. It is for this reason that a majority of the DNA damage encountered in human spermatozoa seems to be oxidative. Given the important role that oxidative stress seems to have in the etiology of DNA damage, there should be an important role for antioxidants in the treatment of this condition. If oxidative DNA damage in spermatozoa is providing a sensitive readout of systemic oxidative stress, the implications of these findings could stretch beyond our immediate goal of trying to minimize DNA damage in spermatozoa as a prelude to assisted conception therapy.

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“…The freezing/thawing process has been shown to generate sperm DNA damage including DNA fragmentation, base modifications, chromatin cross-linking and other alterations, although the exact mechanisms of the cryoinjury to sperm DNA have not been fully elucidated. 4,15,71,72 Recent studies have shown that DNA fragmentation can be primarily attributed to cryopreservation-induced ROS. [73][74][75] In contrast to superoxide anion, the more stable H 2 O 2 readily crosses the plasma membrane and is responsible for DNA oxidative damage.…”

Section: Gangliosides and Spermatozoamentioning

confidence: 99%

“…[10][11][12][13][14] A beneficial effect of the in vitro supplementation of different natural or chemically synthesized antioxidant compounds on human spermatozoa has been observed; however, their effect has also been shown to decrease at inadequate concentrations and, even worse, to behave as pro-oxidants. 11,12,15,16 Herein, we discuss the protective role of exogenous gangliosides against ROS-induced changes based on our studies of human spermatozoa, leukocytes and cell-free systems. Of particular interest are differences between the effects of various types of gangliosides on the lipid peroxidation level, superoxide anion production [17][18][19][20] and H 2 O 2 and cryopreservation-induced DNA damage of human spermatozoa.…”

Section: Introductionmentioning

confidence: 99%

Protective effects of exogenous gangliosides on ROS-induced changes in human spermatozoa

Gavella¹,

Lipovac²

2013

Asian J Androl

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This article summarizes the available evidence on the efficacy of gangliosides to reduce the degree of reactive oxygen species (ROS)-mediated damage. The antioxidative efficacy of exogenous gangliosides in protecting different cells encouraged us to examine their ability to protect human spermatozoa. Gangliosides are sialic acid-containing glycosphingolipids with strong amphiphilic character due to the bulky headgroup made of several sugar rings with sialic acid residues and the double-tailed hydrophobic lipid moiety. The amphiphilicity of gangliosides allows them to exist as micelles in aqueous media when they are present at a concentration above their critical micellar concentration. The protective effect of ganglioside micelles on spermatozoa is believed to stem from their ability to scavenge free radicals and prevent their damaging effects. In our study, we particularly focused our attention on the protective effect of ganglioside micelles on DNA in human spermatozoa exposed to cryopreservation. The results indicate that ganglioside micelles can modulate the hydrophobic properties of the sperm membrane to increase tolerance to DNA fragmentation, thus protecting the DNA from cryopreservation-induced damage. Further actions of ganglioside micelles, which were documented by biochemical and biophysical studies, included (i) the modulation of superoxide anion generation by increasing the diffusion barrier for membrane events responsible for signal translocation to the interior of the cell; (ii) the inhibition of iron-catalysed hydroxyl radical formation due to the iron chelation potential of gangliosides; and (iii) inhibition of hydrogen peroxide diffusion across the sperm membrane.

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Assessment of DNA integrity and morphology of ejaculated spermatozoa from fertile and infertile men before and after cryopreservation

Cited by 228 publications

References 53 publications

Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility

Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility

Apoptosis and DNA damage in human spermatozoa

Protective effects of exogenous gangliosides on ROS-induced changes in human spermatozoa

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