Genome-wide DNA methylation at birth in relation to in utero arsenic exposure and the associated health in later life

Kaushal, Akhilesh; Zhang, Hongmei; Karmaus, Wilfried; Everson, Todd M.; Marsit, Carmen J.; Karagas, Margaret R.; Tsai, Shih-Fen; Wen, H. Joseph; Wang, Shu Li

doi:10.1186/s12940-017-0262-0

Cited by 55 publications

(26 citation statements)

References 64 publications

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“…However, this is difficult to assess, given that enhancers were only interrogated by the most recent MethylationEPIC array, and previous genome-wide studies with EDCs have used the Human Methylation450 array that has fewer probes in enhancer regions [7,58,59]. It is possible that as more studies with environmental exposures are done on arrays that more completely assess enhancer methylation, enrichment at enhancer regions will be more commonly found.…”

Section: Discussionmentioning

confidence: 99%

Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood

et al. 2019

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In 1973, Michigan residents were exposed to polybrominated biphenyl (PBB) when it was accidentally added to farm animal feed. Highly exposed individuals and their children have experienced endocrine-related health problems, though the underlying mechanism behind these remains unknown. We investigated whether PBB exposure is associated with variation in DNA methylation in peripheral blood samples from 658 participants of the Michigan PBB registry using the MethylationEPIC BeadChip, as well as investigated what the potential function of the affected regions are and whether these epigenetic marks are known to associate with endocrine system pathways. After multiple test correction (FDR <0.05), 1890 CpG sites associated with total PBB levels. These CpGs were not enriched in any particular biological pathway, but were enriched in enhancer and insulator regions, and depleted in regions near the transcription start site or in CpG islands (p < 0.05). They were also more likely to be in ARNT and ESR2 transcription factor binding sites (p = 3.27e-23 and p = 1.62e-6, respectively), and there was significant overlap between CpGs associated with PBB and CpGs associated with estrogen (p < 2.2e-16). PBBassociated CpGs were also enriched for CpGs known to be associated with gene expression in blood (eQTMs) (p < 0.05). These eQTMs were enriched for pathways related to immune function and endocrine-related autoimmune disease (FDR <0.05). These results indicate that exposure to PBB is associated with differences in epigenetic marks that suggest that it is acting similarly to estrogen and is associated with dysregulated immune system pathways. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood

et al. 2019

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“…Larger amounts of arsenic are known to be associated with gastrointestinal disturbance and other adverse effects (6)(7)(8). These adverse health hazards could include cancer or other health disorders (5,7,(9)(10)(11)(12). Specifically, exposure to arsenic by ingestion is known to be associated with liver, lung, kidney, and bladder cancer (see reference 13).…”

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confidence: 99%

Exposure to Arsenite in CD-1 Mice during Juvenile and Adult Stages: Effects on Intestinal Microbiota and Gut-Associated Immune Status

Gokulan

Arnold

Jensen

et al. 2018

mBio

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Intestinal microbiota composition and gut-associated immune response can contribute to the toxicity of arsenic. We investigated the potential toxicity of short-term arsenic exposure on gut microbiome composition, intestinal immune status, microbial arsenic resistance gene, and arsenic metabolic profiles in adult and developmental stages of CD-1 mice. The potential toxicity of arsenite [As(III)] was determined for two life stages: (i) adult animals at 24 or 48 h after single gavage (0.05 mg/kg body weight [b.w.] [low dose], 0.1 mg/kg b.w. [medium dose], and 0.2 mg/kg b.w. [high dose]) and repeated exposure at 1 mg/liter for 8 days and (ii) postnatal day 10 (PND10) and PND21 after single gavage (0.05 mg/kg b.w.). Dose- and time-dependent responses in bacterial recovery/microbial composition were observed in adults after a single gavage. Repeated exposure caused a transient decrease in the recovery of intestinal bacteria, a shift in the bacterial population with abundance of arsenic resistance genes, and evidence for host metabolism of arsenite into less-reactive trivalent methylated species. Arsenic exposure in adult animals induced high levels of CC chemokines and of proinflammatory and anti-inflammatory cytokine secretion in intestine. Arsenic exposure at PND21 resulted in the development of distinct bacterial populations. Results of this study highlight significant changes in the intestinal microbiome and gut-associated immune status during a single or repeated exposure to arsenic in juvenile and adult animals. The data warrant investigation of the long-term effects of oral arsenic exposure on the microbiome and of immune system development and responses. Transformation of organic arsenic to toxic inorganic arsenic (iAs) is likely carried out by intestinal bacteria, and iAs may alter the viability of certain microbial populations. This study addressed the impact of arsenic exposure on intestinal microbiota diversity and host gut-associated immune mediators during early development or adulthood using scenarios of acute or repeated doses. During acute arsenic exposure, animals developed defense functions characterized by higher abundances of bacteria that are involved in arsenic resistance or detoxification mechanisms. Arsenite had a negative effect on the abundance of bacterial species that are involved in the conversion of protein to butyrate, which is an alternative energy source in the intestine. The intestinal mucosal immune cytokine profile reflected a mechanism of protection from arsenic toxicity.

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“…Most of the studies have only single timepoint epigenetic measurement taken either early in life with a particular exposure or the later in life with the outcomes. For example, Kaushal et al reported that prenatal arsenic exposure leads to the changes of five CpGs methylation in cord blood which were in the pathways related to cardiovascular diseases; also, the changed DNA methylation was associated with low-density lipoprotein of the children at the age of 2 to 14 years [30]. Additionally, prenatal particulate matter (PM) 2.5 exposure was associated with hypermethylation of children’s nasal epithelia glutathione S-transferase P1 ( GSTP1 ) gene that is also inversely associated with reduced children’s lung function in early childhood [56].…”

Section: Epigenetic Toxicitymentioning

confidence: 99%

Environmentally Induced Epigenetic Plasticity in Development: Epigenetic Toxicity and Epigenetic Adaptation

Tian

Marsit

2018

Curr Epidemiol Rep

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Purpose of Review Epigenetic processes represent important mechanisms underlying developmental plasticity in response to environmental exposures. The current review discusses three classes of environmentally-induced epigenetic changes reflecting two aspects of that plasticity, toxicity effects as well as adaptation in the process of development. Recent findings Due to innate resilience, epigenetic changes caused by environmental exposures may not always lead impairments but may allow the organisms to achieve positive developmental outcomes through appropriate adaptation and a buffering response. Thus, some epigenetic adaptive responses to an immediate stimulus or exposure early in life would be expected to have a survival advantage but these same responses may also result in adverse developmental outcomes as they persists into later life stage. Although accumulating literature has identified environmentally induced epigenetic changes and linked them to health outcomes, we currently face challenges in the interpretation of the functional impact of their epigenetic plasticity. Summary Current environmental epigenetic research suggest that epigenetic processes may serve as a mechanism for resilience, and that they can be considered in terms of their impact on toxicity as a negative outcome, but also on adaptation for improved survival or health. This review encourages epigenetic environmental studies to move deeper inside into the functional meaning of epigenetic plasticity in the development.

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Genome-wide DNA methylation at birth in relation to in utero arsenic exposure and the associated health in later life

Cited by 55 publications

References 64 publications

Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood

Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood

Exposure to Arsenite in CD-1 Mice during Juvenile and Adult Stages: Effects on Intestinal Microbiota and Gut-Associated Immune Status

Environmentally Induced Epigenetic Plasticity in Development: Epigenetic Toxicity and Epigenetic Adaptation

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