Multigenerational epigenetic inheritance in humans: DNA methylation changes associated with maternal exposure to lead can be transmitted to the grandchildren

Sen, Arko; Heredia, Nicole; Senut, Marie Claude; Land, Susan; Hollocher, Kurt; Lu, Xiangyi; Dereski, Mary O.; Ruden, Douglas M.

doi:10.1038/srep14466

Cited by 139 publications

(84 citation statements)

References 52 publications

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“…Notably, Sen et al has also reported that maternal Pb exposure induces epigenetic changes in the germ line of their offspring, impacting DNA methylation in the F2 in humans. These results provide evidence that Pb exposure may induce multigenerational epigenomic changes [63].…”

Section: Leadmentioning

confidence: 57%

“…Related, animal models also foster research examining the transgenerational impacts of exposure. As Sen et al demonstrated, maternal Pb exposure may be related to DNA methylation in the blood of their grandchildren (F2), suggesting that Pb impacts the germ line of a developing fetus [63]. However, assessing truly transgenerational effects is unlikely to be feasible in human populations.…”

Section: Contributions Of Animal Models and In Vitro Experimentsmentioning

confidence: 99%

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Effects of Prenatal Exposure to Endocrine Disruptors and Toxic Metals on The Fetal Epigenome

2017

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Exposure to environmental contaminants during pregnancy has been linked to adverse outcomes at birth and later in life. The link between prenatal exposures and latent health outcomes suggests that these exposures may result in long-term epigenetic reprogramming. Toxic metals and endocrine disruptors are two major classes of contaminants that are ubiquitously present in the environment and represent threats to human health. In this review, we present evidence that prenatal exposures to these contaminants result in fetal epigenomic changes, including altered global DNA methylation, gene-specific CpG methylation and microRNA expression. Importantly, these changes may have functional cellular consequences, impacting health outcomes later in life. Therefore, these epigenetic changes represent a critical mechanism that warrants further study.

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Section: Leadmentioning

confidence: 57%

Section: Contributions Of Animal Models and In Vitro Experimentsmentioning

confidence: 99%

Effects of Prenatal Exposure to Endocrine Disruptors and Toxic Metals on The Fetal Epigenome

2017

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“…Finally, epigenetic changes can be inherited over generations in humans, indicating that if a mother is exposed to a high level of oxygen that induced oxidative stress and resulted in epigenetic changes, thereby up-regulating the GSH system epigenetically, can also be transmitted to the child [35]. This is an adaptive mechanism that prepares the child for future exposure and ensures that its ability to survive is high in the future expected environment.…”

Section: Long Term Adaptation—transcriptional Epigenetic and Genmentioning

confidence: 99%

Time in Redox Adaptation Processes: From Evolution to Hormesis

Sthijns

Weseler

Bast

et al. 2016

IJMS

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Life on Earth has to adapt to the ever changing environment. For example, due to introduction of oxygen in the atmosphere, an antioxidant network evolved to cope with the exposure to oxygen. The adaptive mechanisms of the antioxidant network, specifically the glutathione (GSH) system, are reviewed with a special focus on the time. The quickest adaptive response to oxidative stress is direct enzyme modification, increasing the GSH levels or activating the GSH-dependent protective enzymes. After several hours, a hormetic response is seen at the transcriptional level by up-regulating Nrf2-mediated expression of enzymes involved in GSH synthesis. In the long run, adaptations occur at the epigenetic and genomic level; for example, the ability to synthesize GSH by phototrophic bacteria. Apparently, in an adaptive hormetic response not only the dose or the compound, but also time, should be considered. This is essential for targeted interventions aimed to prevent diseases by successfully coping with changes in the environment e.g., oxidative stress.

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“…Several researchers have used DBS data to gain more insight into different conditions and disorders. DBSs have been even used to study how the effect of the environment can affect several generations as demonstrated by Sen and colleagues in their work on inheritance of epigenetic changes associated with exposure to lead [58].…”

Section: B Secondary Use Of Patient Data For Genomic Research and Tomentioning

confidence: 99%

Secondary Use and Analysis of Big Data Collected for Patient Care

Martín-Sánchez¹,

Aguiar-Pulido²,

Lopez-Campos³

et al. 2017

Yearb Med Inform

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SummaryObjectives: To identify common methodological challenges and review relevant initiatives related to the re-use of patient data collected in routine clinical care, as well as to analyze the economic benefits derived from the secondary use of this data. Through the use of several examples, this article aims to provide a glimpse into the different areas of application, namely clinical research, genomic research, study of environmental factors, and population and health services research. This paper describes some of the informatics methods and Big Data resources developed in this context, such as electronic phenotyping, clinical research networks, biorepositories, screening data banks, and wide association studies. Lastly, some of the potential limitations of these approaches are discussed, focusing on confounding factors and data quality. Methods: A series of literature searches in main bibliographic databases have been conducted in order to assess the extent to which existing patient data has been repurposed for research. This contribution from the IMIA working group on "Data mining and Big Data analytics" focuses on the literature published during the last two years, covering the timeframe since the working group's last survey. Results and Conclusions: Although most of the examples of secondary use of patient data lie in the arena of clinical and health services research, we have started to witness other important applications, particularly in the area of genomic research and the study of health effects of environmental factors. Further research is needed to characterize the economic impact of secondary use across the broad spectrum of translational research.

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Multigenerational epigenetic inheritance in humans: DNA methylation changes associated with maternal exposure to lead can be transmitted to the grandchildren

Cited by 139 publications

References 52 publications

Effects of Prenatal Exposure to Endocrine Disruptors and Toxic Metals on The Fetal Epigenome

Effects of Prenatal Exposure to Endocrine Disruptors and Toxic Metals on The Fetal Epigenome

Time in Redox Adaptation Processes: From Evolution to Hormesis

Secondary Use and Analysis of Big Data Collected for Patient Care

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