DNA oxidative damage in mammalian spermatozoa: where and why is the male nucleus affected?

Noblanc, Anaïs; Damon-Soubeyrand, Christelle; Karrich, Bouchta; Henry-Berger, Joëlle; Cadet, Rémi; Saez, Fabrice; Guiton, Rachel; Janny, L.; Pons-Rejraji, Hanae; Álvarez, Juan G.; Drevet, Joël R.; Kocer, Ayhan

doi:10.1016/j.freeradbiomed.2013.07.044

Cited by 74 publications

(79 citation statements)

References 27 publications

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“…In a recent analysis of oxidative DNA damage in the GPx5 knockout mouse, it was observed that the major sites of such damage involve histone-rich interlinker regions located at the periphery of the spermatozoon nucleus in close association with the nuclear matrix, where they interconnect the protamine-dominated toroids. Such regions are thought to contain genes that are primed for expression in the early embryo, and as a result their disruption would be expected to have a significant impact on the normality of development [22]. …”

Section: Accumulation Of Sperm Dna Damage Results In De Novo Mutationmentioning

confidence: 99%

Paternal Obesity, Interventions, and Mechanistic Pathways to Impaired Health in Offspring

et al. 2014

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Background: The global rates of male overweight/obesity are rising, approaching 70% of the total adult population in Western nations. Overweight/obesity increases the risk of chronic diseases; however, there is increasing awareness that male obesity negatively impacts fertility, subsequent pregnancy, and the offspring health burden. Developmental programming is well defined in mothers; however, it is becoming increasingly evident that developmental programming can be paternally initiated and mediated through paternal obesity. Key Messages: Both human and rodent models have established that paternal obesity impairs sex hormones, basic sperm function, and molecular composition. This results in perturbed embryo development and health and an increased subsequent offspring disease burden in both sexes. The reversibility of obesity-induced parental programming has only recently received attention. Promising results in animal models utilizing diet and exercise interventions have shown improvements in sperm function and molecular composition, resulting in restorations of both embryo and fetal health and subsequent male offspring fertility. The direct mode for paternal inheritance is likely mediated via spermatozoa. We propose two main theories for the origin of male obesity-induced paternal programming: (1) accumulation of sperm DNA damage resulting in de novo mutations in the embryo and (2) changes in sperm epigenetic marks (microRNA, methylation, or acetylation) altering the access, transcription, and translation of paternally derived genes during early embryogenesis. Conclusions: Paternal overweight/obesity induces paternal programming of offspring phenotypes likely mediated through genetic and epigenetic changes in spermatozoa. These programmed changes to offspring health appear to be partially restored via diet/exercise interventions in obese fathers preconception, which have been shown to improve aspects of sperm DNA integrity. However, the majority of data surrounding paternal obesity and offspring phenotypes have come from rodent models; therefore, we contend that it will be increasingly important to study population-based data to determine the likely mode of inheritance in humans.

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Section: Accumulation Of Sperm Dna Damage Results In De Novo Mutationmentioning

confidence: 99%

Paternal Obesity, Interventions, and Mechanistic Pathways to Impaired Health in Offspring

et al. 2014

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“…This finding demonstrates that histones are not randomly distributed in the sperm genome; they are associated with specific genes, and make up the linker regions between each protamine-bound toroid, which are the sites with the highest nuclease sensitivity (49). It is these areas that are actually assessed by the majority of chromatin status tests (50).…”

Section: Understanding Dna Fragmentation's Originsmentioning

confidence: 97%

“…Nevertheless, the end result is that approximately 16% to 20% of histone-bound DNA persists, and not simply as the result of an incomplete process of reshaping the gamete's phenotype. These areas of readily transcribable DNA that are essential in the pre-fertilization steps (36) play a specific role during male germ cell maturation; in addition, they are the portions of sperm chromatin that are more sensitive to damage (23,98) and that are reachable by most of the DNA fragmentation assays (50).…”

Section: Figurementioning

confidence: 99%

Perspectives on the assessment of human sperm chromatin integrity

Palermo

Neri

Cozzubbo

et al. 2014

Fertility and Sterility

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“…The 8-OHdG oxidative lesion, the most characterised in sperm, co-localises to the nuclear matrix and histonebound DNA (Noblanc et al 2013). Sperm cannot repair 8-OHdG lesions as they only contain the first enzyme in the base excision repair pathway (OGG1) and subsequently rely on the oocyte's enzymes required to complete this process after fertilisation (Smith et al 2013), which if overwhelmed by the abundance of 8-OHdG lesions could theoretically lead to the incorporation of mismatched 234:2 bases and an increased mutation load in the resutlant embryo/offspring.…”

Section: Oxidative Dna Damagementioning

confidence: 99%

The most common vices of men can damage fertility and the health of the next generation

Fullston

McPherson

Zander-Fox

et al. 2017

Journal of Endocrinology

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Animal and human studies demonstrate that acquired paternal traits can impair both a male’s fertility and the health of his offspring, including advanced age, smoking, stress, trauma, under-nutrition, infection, toxin exposure, and obesity. Many of these factors lead to similar changes to neurological, behavioural, and/or metabolic functioning in offspring. The molecular mechanisms that both respond to the paternal environment and act to transmit traits to offspring are beginning to emerge. This review focuses on three vices of men (alcohol consumption, overweight/obesity, and tobacco smoking) that damage fertility and pose risks to offspring health. These vices are not only the three most prevalent but are also leading risk factors for death and disability adjusted life years (DALYs) worldwide. Moreover, given that these vices are predominantly self-inflicted, interventions aimed at mitigating their consequences are readily identified.

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DNA oxidative damage in mammalian spermatozoa: where and why is the male nucleus affected?

Cited by 74 publications

References 27 publications

Paternal Obesity, Interventions, and Mechanistic Pathways to Impaired Health in Offspring

Paternal Obesity, Interventions, and Mechanistic Pathways to Impaired Health in Offspring

Perspectives on the assessment of human sperm chromatin integrity

The most common vices of men can damage fertility and the health of the next generation

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