DNA Damage in Human and Mouse Spermatozoa after In Vitro-Irradiation Assessed by the Comet Assay

Haines, G.; Marples, Brian; Daniel, Paul E.; Morris, Ian D.

doi:10.1007/978-1-4899-0089-0_10

Cited by 97 publications

(61 citation statements)

References 43 publications

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“…DOI 10.1002/em cant levels of DNA damage immediately after radiation followed by a significant decline during the first 2 hr. These results are in agreement with the known decrease in radiosensitivity of maturing male germ cells, which has been linked to chromatin condensation and replacement of histones with protamines in these cells [Joshi et al, 1990;van Loon et al, 1993;Haines et al, 1998]. In addition, they reflect the proficiency of testicular cells in both Non Homologous End Joining (NHEJ) and Homologous Recombination (HR)-mediated repair [Srivastava and Raman, 2007;Ahmed et al, 2007Ahmed et al, , 2010a.…”

Section: Discussionsupporting

confidence: 86%

Direct and delayed X‐ray‐induced DNA damage in male mouse germ cells

Cordelli¹,

Eleuteri²,

Grollino³

et al. 2012

Environ and Mol Mutagen

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Sperm DNA integrity is essential for the accurate transmission of paternal genetic information. Various stages of spermatogenesis are characterized by large differences in radiosensitivity. Differentiating spermatogonia are susceptible to radiationinduced cell killing, but some of them can repair DNA damage and progress through differentiation. In this study, we applied the neutral comet assay, immunodetection of phosphorylated H2AX (g-H2AX) and the Sperm Chromatin Structure Assay (SCSA) to detect DNA strand breaks in testicular cells and spermatozoa at different times following in vivo X-ray irradiation. Radiation produced DNA strand breaks in testicular cells that were repaired within the first few hours after exposure. Spermatozoa were resistant to the induction of DNA damage, but non-targeted DNA lesions were detected in spermatozoa derived from surviving irradiated spermatogonia. These lesions formed while round spermatids started to elongate within the testicular seminiferous tubules. The transcription of pro-apoptotic genes at this time was also enhanced, suggesting that an apoptotic-like process was involved in DNA break production. Our results suggest that proliferating spermatogonia retain a memory of the radiation insult that is recognized at a later developmental stage and activates a process leading to DNA fragmentation. Environ. Mol. Mutagen. 53:429-439, 2012. V V C 2012 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 86%

Direct and delayed X‐ray‐induced DNA damage in male mouse germ cells

Cordelli¹,

Eleuteri²,

Grollino³

et al. 2012

Environ and Mol Mutagen

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“…In experimental studies on mice, sperm DNA damage has been associated with chromosomal abnormalities, developmental loss, reduced longevity and birth defects [14,18,24]. In humans, advanced paternal age is associated with rare autosomal dominant diseases such as achondroplasia and Apert's syndrome, both due to point mutations, but whether these mutations are related to the global integrity of the sperm DNA, as measured by tests such as the sperm chromatin structure assay, remains to be verified [21,22].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have also demonstrated that sperm DNA damage is associated with advanced paternal age and poor semen parameters [11,16,26,27,34]. Increased levels of sperm DNA damage have been linked with chromosomal abnormalities, developmental loss and birth defects in mouse model systems [18,24]. Various mechanisms have been proposed to explain the increase in sperm DNA damage with age, ranging from oxidative stress to inefficient apoptosis processes [31].…”

Section: Introductionmentioning

confidence: 99%

High prevalence of isolated sperm DNA damage in infertile men with advanced paternal age

Das

Alhathal

San-Gabriel

et al. 2013

J Assist Reprod Genet

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Background Sperm DNA damage is associated with male infertility, lower pregnancy rates and pregnancy loss. Objective The primary aim of our study was to evaluate the prevalence of sperm DNA damage in younger and older men with normozoospermia. Design, Setting and Participants We obtained semen from 277 consecutive non-azoospermic men presenting for sperm DNA testing. Outcome Measurements and Statistical Analysis The main outcome measures included sperm % DNA fragmentation index (%DFI, using sperm chromatin structure assay), sperm concentration, motility and morphology, and, paternal age.Results and Limitations Sperm % DFI was positively correlated with paternal age (r=0.20, P<0.001) and inversely correlated % progressive motility (r=−0.16, P=0.01). Sperm %DFI was significantly higher in older (≥40 years) compared to younger (<40 years) normozoospermic men (17±13 vs. 12±8, respectively P=0.008), whereas, sperm concentration, progressive motility and morphology were not significantly different in these two groups. Moreover, the prevalence of high levels of sperm DNA damage (>30 % DFI) was significantly higher in older compared to younger normozoospermic men (17 % vs. 3 %, respectively, P<0.001). Conclusion The data indicate that a conventional semen analysis can often fail to detect a defect in spermatogenesis (high %DFI) in older men and suggest that infertile couples with advanced paternal age, including those with normal semen parameters, should consider sperm DNA testing as part of the couple evaluation.

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“…DNA strand breaks release supercoiling and allow migration of fragmented DNA to occur in the direction of the anode (Haines et al, 1998). Spermatozoa with high levels of DNA strand breaks have increased comet tail fluorescent intensity (Hughes et al, 1996) and comet tail length (Singh and Stephens, 1998).…”

Section: Comet Assaymentioning

confidence: 99%

Sperm Chromatin Structure Assay: Its Clinical Use for Detecting Sperm DNA Fragmentation in Male Infertility and Comparisons With Other Techniques

Evenson

Larson

Jost

2002

Journal of Andrology

905

768

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The Sperm Chromatin Structure Assay (SCSA) was first described in the December 5, 1980 issue of Science (Evenson et al, 1980a). The data described in that article showed a significant difference between proven fertile and subfertility or infertility in men and bulls and the susceptibility to denaturation of their sperm nuclear DNA. A subsequent study (Evenson et al, 1984) described SCSA data obtained from men with testicular cancer. The data were heterogeneous, and begged the question, what was SCSA measuring? Great effort has been spent over the past 15 years on animal model systems, mostly related to dose-response toxicology experiments and large animal fertility trials. The results from these studies showed that SCSA was highly dose-responsive to toxicants, highly repeatable, and provided meaningful biological information on sperm nuclear DNA defects. The extensive data from nonhumans (Evenson et al, 1985(Evenson et al, , 1989a(Evenson et al, ,b, 1993a(Evenson et al, ,b,c, 1994Ballachey et al, 1987Ballachey et al, , 1988Evenson and Jost, 1993; Sailer et al, 1995a,b;Evenson, 1999a), and human toxicology and fertility studies (Evenson et al, 1978(Evenson et al, , 1980a(Evenson et al, ,b, 1984(Evenson et al, , 1991Evenson and Melamed, 1983;Evenson, 1999b;Larson et al, 1999Larson et al, , 2000Larson et al, , 2001 provide This work was supported in part by grant R827019 from the US Environmental Protection Agency, grants EPS-9720642 and OSR-9452894 from the National Science Foundation, and by SCSA Diagnostics, Inc. This is South Dakota Agricultural Experiment Station publication 3273 of the journal series.Correspondence to: Donald P. Evenson, Olson Biochemistry Laboratories, ASC 136, South Dakota State University, Brookings, SD 57006 (e-mail: donald evenson@sdstate.edu).Received for publication September 20, 2001; accepted for publication September 20, 2001. compelling evidence that SCSA will be useful in clinical human semen analysis (Figure 1).After reviewing current infertility center sites on the World Wide Web and approximately a dozen lay-oriented books on infertility and assisted reproductive technology (ART), it was amazing that not a single reference contained any information about the negative influence of fragmented sperm nuclear DNA on successful pregnancy outcome. Furthermore, few physicians are aware of scientific literature on this subject. Currently, if a spermatozoon has some motility as seen under a light microscope, and reasonable morphology, then many ART clinics assume that the sperm DNA must be fine. However, a number of cases have been documented in which couples have had multiple failed attempts at intracytoplasmic sperm injection (ICSI), even using donor eggs, and we found that the fragmentation of sperm DNA was above our threshold for less than 1% probability of achieving a successful pregnancy. Spermatozoa with defective DNA can fertilize an oocyte, produce high-quality early stage embryos, and then, in relationship to the extent of DNA damage, fail in producing a successful term ...

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DNA Damage in Human and Mouse Spermatozoa after In Vitro-Irradiation Assessed by the Comet Assay

Cited by 97 publications

References 43 publications

Direct and delayed X‐ray‐induced DNA damage in male mouse germ cells

Direct and delayed X‐ray‐induced DNA damage in male mouse germ cells

High prevalence of isolated sperm DNA damage in infertile men with advanced paternal age

Sperm Chromatin Structure Assay: Its Clinical Use for Detecting Sperm DNA Fragmentation in Male Infertility and Comparisons With Other Techniques

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