Early Life Lead Exposure Causes Gender-Specific Changes in the DNA Methylation Profile of DNA Extracted from Dried Blood Spots

Sen, Arko; Heredia, Nicole; Senut, Marie Claude; Hess, Matthew; Land, Susan; Wen, Qian; Hollacher, Kurt; Dereski, Mary O.; Ruden, Douglas M.

doi:10.2217/epi.15.2

Cited by 83 publications

(71 citation statements)

References 66 publications

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“…Additional studies have focused on the sex-specific effects of Pb-induced epigenetic disruptions of the fetus. Using cord blood and blood spots, Sen et al examined differentially methylated regions of the genome that may serve as sex-dependent or independent biomarkers of Pb exposure [61,62]. Interestingly, different patterns were noted when observing CpG methylation in cord blood versus infant blood spots.…”

Section: Leadmentioning

confidence: 99%

“…However, in blood spots, females showed greater disruption in CpG methylation. Given that males tend to be more susceptible to the effects of Pb exposure, researchers concluded that disruptions in CpG methylation may be adaptive in blood [62]. 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.…”

Section: Leadmentioning

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: 99%

Section: Leadmentioning

confidence: 99%

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

2017

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“…Previous studies examining whole blood stored for twelve months at RT in a DNA-protecting solution [17] or placenta tissue stored for two days at RT [33] identified no major DNA methylation changes. Moreover, the feasibility of genome-wide DNA methylation studies using DNA from post-mortem brains [34], as well as archived dried blood spots has also been described before [15,35,36]. To our knowledge this is the first report of a genome-wide interrogation of the DNA methylome in matched whole blood samples stored at RT.…”

Section: Discussionmentioning

confidence: 84%

The Genome-Wide DNA Methylation Profile of Peripheral Blood Is Not Systematically Changed by Short-Time Storage at Room Temperature

et al. 2017

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Abstract:Background: Epigenetic epidemiology has proven an important research discipline in the delineation of diseases of complex etiology. The approach, in such studies, is often to use bio-banked clinical material, however, many such samples were collected for purposes other than epigenetic studies and, thus, potentially not processed and stored appropriately. The Danish National Birth Cohort (DNBC) includes more than 100,000 peripheral and umbilical cord blood samples shipped from maternity wards by ordinary mail in EDTA tubes. While this and other similar cohorts hold great promises for DNA methylation studies the potential systematic changes prompted by storage at ambient temperatures have never been assessed on a genome-wide level. Methods and Results: In this study, matched EDTA whole blood samples were stored up to three days at room temperature prior to DNA extraction and methylated DNA immunoprecipitation coupled with deep sequencing (MeDIP-seq). We established that the quality of the MeDIP-seq libraries was high and comparable across samples; and that the methylation profiles did not change systematically during the short-time storage at room temperature. Conclusion: The global DNA methylation profile is stable in whole blood samples stored for up to three days at room temperature in EDTA tubes making genome-wide methylation studies on such material feasible.

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“…Nevertheless, genetic diversity clearly modifies the body's response to developmental Pb exposure even if the evidence is not detailed [15][16][17][18]. Gender also plays a part, through epigenetics [19]. Children are more at risk from Pb exposure than adults because of their hand to mouth activity, higher respiratory rates and higher gastrointestinal absorption per unit body weight.…”

Section: Causes Of Ill Healthmentioning

confidence: 99%

Environment and Human Health: The Challenge of Uncertainty in Risk Assessment

Stewart

Hursthouse

2018

Geosciences

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High quality and accurate environmental investigations and analysis are essential to any assessment of contamination and to the decision-making process thereafter. Remediation decisions may be focused by health outcomes, whether already present or a predicted risk. The variability inherent in environmental media and analysis can be quantified statistically; uncertainty in models can be reduced by additional research; deep uncertainty exists when environmental or biomedical processes are not understood, or agreed upon, or remain uncharacterized. Deep uncertainty is common where health and environment interact. Determinants of health operate from the individual's genes to the international level; often several levels act synergistically. We show this in detail for lead (Pb). Pathways, exposure, dose and response also vary, modifying certainty. Multi-disciplinary approaches, built on high-quality environmental investigations, enable the management of complex and uncertain situations. High quality, accurate environmental investigations into pollution issues remain the cornerstone of understanding attributable health outcomes and developing appropriate responses and remediation. However, they are not sufficient on their own, needing careful integration with the wider contexts and stakeholder agendas, without which any response to the environmental assessment may very well founder. Such approaches may benefit more people than any other strategy.

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Early Life Lead Exposure Causes Gender-Specific Changes in the DNA Methylation Profile of DNA Extracted from Dried Blood Spots

Cited by 83 publications

References 66 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

The Genome-Wide DNA Methylation Profile of Peripheral Blood Is Not Systematically Changed by Short-Time Storage at Room Temperature

Environment and Human Health: The Challenge of Uncertainty in Risk Assessment

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