DNA methylation and potential multigenerational epigenetic effects linked to uranium chronic low-dose exposure in gonads of males and females rats

Elmhiri, Ghada; Gloaguen, C.; Grison, Stéphane; Kereselidze, Dimitri; Elie, Christelle; Tack, Karine; Benderitter, Marc; Lestaevel, Philippe; Legendre, Audrey; Souidi, Maâmar

doi:10.1016/j.toxlet.2017.10.004

Cited by 31 publications

(12 citation statements)

References 29 publications

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“…The mRNA and protein expression levels of the DNMT3A gene in cancerous testicular tissues were significantly higher than those of the DNMT3A gene in normal testicular tissues (Chen et al 2014). Chronic low-dose exposure to uranium increased the global methylation level in the rat testes as well as the mRNA expression levels of the DNA methyltransferase genes DNMT1 and DNMT3A/B; this DNA methylation profile was maintained across generations (Elmhiri et al 2018). Here, both mRNA and protein expression levels of the three DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) were significantly lower in the TP testicular tissues than those in the YP testicular tissues.…”

Section: Discussionmentioning

confidence: 91%

DNA Methylation may be a testicular plateau adaptation in Tibetan pig

Zhao

Tian

Cheng

et al. 2021

Journal of Applied Animal Research

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DNA methylation plays an important role in reproduction. Tibetan pigs maintain high sperm motility, even under extreme conditions at high altitudes. However, the DNA methylation mechanisms underlying testicular plateau adaptations in Tibetan pigs remain unclear. We determined the genomic DNA methylation level in the testicular tissues of Tibetan pigs living at high altitudes (TP) and of Yorkshire pigs that migrated to high altitudes (YP) using the fluorescence method. Quantitative realtime PCR and western blots were used to measure the gene and protein expression levels, respectively, of three DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) and hypoxia-inducible factor 2α (HIF2α). We found that the genomic DNA methylation level and the mRNA and protein expression levels of the four genes were all significantly lower in the testicular tissues of TP than YP. In short, compared with YP, the downregulation of DNA methyltransferases in the TP testes led to lower levels of genomic DNA methylation, which would facilitate higher sperm motility. Meanwhile, HIF2α expression in the TP testes was down-regulated, which might contributes to TP testes' adaption to the plateau environment. This study provided new insights into the DNA methylation mechanisms underlying plateau adaptations in TP testicles.

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Section: Discussionmentioning

confidence: 91%

DNA Methylation may be a testicular plateau adaptation in Tibetan pig

Zhao

Tian

Cheng

et al. 2021

Journal of Applied Animal Research

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“…For example, exposure to low doses of uranium causes hypermethylation in testis and hypomethylation in ovaries with significant changes in the expression of DNA methyltransferase genes DNMT1 and DNMT3A/B [36]. The effects are maintained across F0, F1, and F2 generations [36]. The sensitivity of DNA methylation changes with age has also been reported: global DNA hypermethylation was found to be associated with high serum levels of persistent organic pollutants in an elderly population [37].…”

Section: Epigenetic Regulation Via Dna Methylationmentioning

confidence: 94%

“…It was suggested that exposure to toxic compounds causes changes in DNA methylation patterns. For example, exposure to low doses of uranium causes hypermethylation in testis and hypomethylation in ovaries with significant changes in the expression of DNA methyltransferase genes DNMT1 and DNMT3A/B [36]. The effects are maintained across F0, F1, and F2 generations [36].…”

Section: Epigenetic Regulation Via Dna Methylationmentioning

confidence: 99%

Transgenerational Inheritance of Environmentally Induced Epigenetic Alterations during Mammalian Development

Legoff

D’Cruz

Tevosian

et al. 2019

Cells

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Genetic studies traditionally focus on DNA as the molecule that passes information on from parents to their offspring. Changes in the DNA code alter heritable information and can more or less severely affect the progeny’s phenotype. While the idea that information can be inherited between generations independently of the DNA’s nucleotide sequence is not new, the outcome of recent studies provides a mechanistic foundation for the concept. In this review, we attempt to summarize our current knowledge about the transgenerational inheritance of environmentally induced epigenetic changes. We focus primarily on studies using mice but refer to other species to illustrate salient points. Some studies support the notion that there is a somatic component within the phenomenon of epigenetic inheritance. However, here, we will mostly focus on gamete-based processes and the primary molecular mechanisms that are thought to contribute to epigenetic inheritance: DNA methylation, histone modifications, and non-coding RNAs. Most of the rodent studies published in the literature suggest that transgenerational epigenetic inheritance through gametes can be modulated by environmental factors. Modification and redistribution of chromatin proteins in gametes is one of the major routes for transmitting epigenetic information from parents to the offspring. Our recent studies provide additional specific cues for this concept and help better understand environmental exposure influences fitness and fidelity in the germline. In summary, environmental cues can induce parental alterations and affect the phenotypes of offspring through gametic epigenetic inheritance. Consequently, epigenetic factors and their heritability should be considered during disease risk assessment.

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“…Considerations for how epigenetic effects from environmental exposures may contribute to increased rates of disease presentations in AI populations have not been investigated to date. This is despite the increasing and ongoing research in animal models demonstrating the potential for multigenerational epigenetic health effects from low-dose uranium exposure (Elmhiri et al 2018;Legendre et al 2019). With developing technologies in the field of epigenetics, future research in this area could elucidate transgenerational risk factors that have yet to be formally identified in humans.…”

Section: American Indian Considerationsmentioning

confidence: 99%

Uranium Exposure in American Indian Communities: Health, Policy, and the Way Forward

Redvers

Chischilly²,

Warne

et al. 2021

Environ Health Perspect

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Background: Uranium contamination of drinking-water sources on American Indian (AI) reservations in the United States is a largely ignored and underfunded public health crisis. With an estimated 40% of the headwaters in the western U.S. watershed, home to many AI reservation communities, being contaminated with untreated mine waste, the potential health effects have largely been unexplored. With AI populations already facing continued and progressive economic and social marginalization, higher prevalence of chronic disease, and systemic discrimination, associations between various toxicant exposures, including uranium, and various chronic conditions, need further examination. Objectives: Uranium’s health effects, in addition to considerations for uranium drinking-water testing, reporting, and mitigation in reference to AI communities through the lens of water quality, is reviewed. Discussion: A series of environmental health policy recommendations are described with the intent to proactively improve responsiveness to the water quality crisis in AI reservation communities in the United States specific to uranium. There is a serious and immediate need for better coordination of uranium-related drinking-water testing and reporting on reservations in the United States that will better support and guide best practices for uranium mitigation efforts. https://doi.org/10.1289/EHP7537

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DNA methylation and potential multigenerational epigenetic effects linked to uranium chronic low-dose exposure in gonads of males and females rats

Abstract: Altogether, our work demonstrates for the first time a sex-dependance and inheritance of epigenetic marks, DNA methylation, as a biological response to the exposure to low doses of uranium. However, it is not clear which type of reproductive cell type is more responsive in this context.

Cited by 31 publications

References 29 publications

DNA Methylation may be a testicular plateau adaptation in Tibetan pig

DNA Methylation may be a testicular plateau adaptation in Tibetan pig

Transgenerational Inheritance of Environmentally Induced Epigenetic Alterations during Mammalian Development

Uranium Exposure in American Indian Communities: Health, Policy, and the Way Forward

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