How do male germ cells handle DNA damage?

Olsen, Ann‐Karin; Lindeman, Birgitte; Wiger, Richard; Duale, Nur; Brunborg, Gunnar

doi:10.1016/j.taap.2005.01.060

Cited by 112 publications

(76 citation statements)

References 60 publications

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“…Our results confirm and extend prior studies of the DNA repair-deficient window during spermiogenesis [13][14][15][16][17][18][19][20]. The results of our experiments showed that the frequencies of zygotes with chromosomal aberrations were significantly higher when a total dose of 28 mg/kg DEB was given over days 14 through 8 before mating than when it was given as a single dose 14 days before mating (Table 2 and Figure 3A).…”

Section: Discussionsupporting

confidence: 90%

“…These results show that the last two weeks of mouse spermiogenesis, which corresponds to the period of spermatogenesis that is thought to be DNA repair-deficient in prior studies [13][14][15][16][17][18][19][20], is also the sensitive window for induction of chromosomal aberrations in sperm after paternal exposure to DEB, and that both sperm and late spermatids are unable to repair DEB-induced damage.…”

Section: Chromosomal Aberrations Detected In Zygotes After Repeated Ementioning

confidence: 52%

“…It has been proposed that post-meiotic male germ cells are susceptible to the accumulation of DNA lesions in the fertilizing sperm because the DNA repair capacity declines during the latter part of spermiogenesis [17]. Our results provide two lines of evidence in support for the accumulation of heritable lesions during the last two weeks of spermiogenesis: (i) the frequencies of zygotes with chromosomal aberrations found after exposing male mice to DEB for two or three weeks were not different from those expected based on the results of the one-week exposures that covered the same period of spermiogenesis (Table 1); (ii) DEB administration as either single dose seven days before mating or distributed over the last seven days immediately before mating produced similar frequencies of zygotes with paternally-derived chromosomal aberrations (Table 3).…”

Section: Discussionmentioning

confidence: 99%

“…The high sensitivity of the postmeiotic period to mutagenic exposure has been associated with the reduced DNA repair capacity of late spermatids and sperm as compared to early spermatids and other spermatogenic cell types [13][14][15][16][17]. All major DNA repair pathways seem to be less functional in late spermatids and sperm [17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

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DNA repair decline during mouse spermiogenesis results in the accumulation of heritable DNA damage

Marchetti

Wyrobek

2008

DNA Repair

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The post-meiotic phase of mouse spermatogenesis (spermiogenesis) is very sensitive to the genomic effects of environmental mutagens because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. We hypothesized that repeated exposures to mutagens during this repair-deficient phase result in the accumulation of heritable genomic damage in mouse sperm that leads to chromosomal aberrations in zygotes after fertilization. We used a combination of single or fractionated exposures to diepoxybutane (DEB), a component of tobacco smoke, to investigate how differential DNA repair efficiencies during the three weeks of spermiogenesis affected the accumulation of DEB-induced heritable damage in early spermatids (21-15 days before fertilization, dbf), late spermatids (14-8 dbf) and sperm (7-1 dbf). Analysis of chromosomal aberrations in zygotic metaphases using PAINT/DAPI showed that late spermatids and sperm are unable to repair DEB-induced DNA damage as demonstrated by significant increases (P<0.001) in the frequencies of zygotes with chromosomal aberrations. Comparisons between single and fractionated exposures suggested that the DNA repair-deficient window during late spermiogenesis may be less than two weeks in the mouse and that during this repair-deficient window there is accumulation of DNA damage in sperm.Finally, the dose-response study in sperm indicated a linear response for both single and repeated exposures. These findings show that the differential DNA repair capacity of post-meioitic male germ cells has a major impact on the risk of paternally transmitted heritable damage and suggest that chronic exposures that may occur in the weeks prior to fertilization because of occupational or lifestyle factors (i.e, smoking) can lead to an accumulation of genetic damage in sperm and result in heritable chromosomal aberrations of paternal origin.

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Section: Discussionsupporting

confidence: 90%

Section: Chromosomal Aberrations Detected In Zygotes After Repeated Ementioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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DNA repair decline during mouse spermiogenesis results in the accumulation of heritable DNA damage

Marchetti

Wyrobek

2008

DNA Repair

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“…The organisation of the sperm chromatin is unique, as histone proteins are eventually replaced by transition proteins and finally by protamines, resulting in an extremely compact, condensed DNA (Dadoune, 1995;Sakkas et al, 1999). Proper condensation may stabilise the DNA and make it less sensitive to oxidative damage; however, mature spermatozoa are not able to repair DNA damage (Olsen et al, 2005).…”

mentioning

confidence: 99%

Flow cytometric detection of oxidative DNA damage in fish spermatozoa exposed to cadmium — Short communication

Nagy

Kakasi

Bercsényi

2016

Acta Veterinaria Hungarica

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The aim of the present pilot study was to apply a flow cytometric assay, the so-called OxyDNA test, to determine the level of oxidative DNA damage in fish spermatozoa exposed to different concentrations (0.01-10,000 mg/L) of cadmium. Milt was collected from three randomly selected Prussian carp (Carassius auratus gibelio) males. Oxidative DNA damage was assessed with the OxyDNA kit and using flow cytometry. The ratio of OxyDNA-positive events increased significantly at higher cadmium concentrations. The results indicate that direct contact of fish spermatozoa with cadmium-polluted water initiates genotoxic damage.

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Monoallelic gene expression and mammalian evolution

Keverne

2009

BioEssays

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Monoallelic gene expression has played a significant role in the evolution of mammals enabling the expansion of a vast repertoire of olfactory receptor types and providing increased sensitivity and diversity. Monoallelic expression of immune receptor genes has also increased diversity for antigen recognition, while the same mechanism that marks a single allele for preferential rearrangement also provides a distinguishing feature for directing hypermutations. Random monoallelic expression of the X chromosome is necessary to balance gene dosage across sexes. In marsupials only the maternal X chromosome is expressed, while in eutherian mammals the paternal X genes are silenced in the developing placenta and early blastocyst. These examples of epigenetic gene regulation commonly employ asynchrony of replication, the binding of polycomb proteins and antisense RNA, and histone modifications to chromatin structure. The same is true for genomic imprinting which among vertebrates is unique to mammals and represents a special kind of epigenetic modification that is heritable according to parent of origin. Genomic imprinting pervades many aspects of mammalian growth and evolution but in particular has played a significant role in the co-adaptive evolution of the mother and foetus.

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How do male germ cells handle DNA damage?

Cited by 112 publications

References 60 publications

DNA repair decline during mouse spermiogenesis results in the accumulation of heritable DNA damage

DNA repair decline during mouse spermiogenesis results in the accumulation of heritable DNA damage

Flow cytometric detection of oxidative DNA damage in fish spermatozoa exposed to cadmium — Short communication

Monoallelic gene expression and mammalian evolution

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