Biological memories of past environments: Epigenetic pathways to health disparities

Human health tends to mirror gradients in social standing related to class, ethnicity and race. Past research in the social sciences suggests that environmental experiences related to social status contribute to these disparities, but the underlying biological mechanisms are only partially understood. Here, we review research related to three domains of environmental exposure that point to epigenetic contributions to health disparities: nutrition, psychosocial stress, and environmental toxicant exposure. Each exposure has effects that may persist across the life course and in some instances may be transmitted to offspring via epigenetic inheritance. Since epigenetic markings provide a "memory" of past experiences, minimizing future disparities in health will be partially contingent upon our ability to address inequality in the current environment. We suggest that future research in environmental epigenetics focus on establishing the reversibility of stress-induced epigenetic modifications, and also on identifying positive epigenetic effects of environmental enrichment.     

Sources of stress in captivity

Animals housed in artificial habitats are confronted by a wide range of potentially provocative environmental challenges. In this article, we review many of the potential stressors that may adversely affect animals living in captivity. These include abiotic, environmental sources of stress such as artificial lighting, exposure to loud or aversive sound, arousing odors, and uncomfortable temperatures or substrates. In addition, confinement-specific stressors such as restricted movement, reduced retreat space, forced proximity to humans, reduced feeding opportunities, maintenance in abnormal social groups, and other restrictions of behavioral opportunity are considered. Research in support of the claims for these environmental elements as stressors for captive animals reveals no unique suite of behavioral or physiological responses that will clearly indicate the cause of those responses; rather, it is up to us as managers and caretakers of animals in captivity to evaluate enclosures and husbandry practices to ensure the optimal well-being of animals in our care.     

A veterinary perspective on One Health in the Arctic

Exposure to long-range transported industrial chemicals, climate change and diseases is posing a risk to the overall health and populations of Arctic wildlife. Since local communities are relying on the same marine food web as marine mammals in the Arctic, it requires a One Health approach to understand the holistic ecosystem health including that of humans. Here we collect and identify gaps in the current knowledge of health in the Arctic and present the veterinary perspective of One Health and ecosystem dynamics. The review shows that exposure to persistent organic pollutants (POPs) is having multiple organ-system effects across taxa, including impacts on neuroendocrine disruption, immune suppression and decreased bone density among others. Furthermore, the warming Arctic climate is suspected to influence abiotic and biotic long-range transport and exposure pathways of contaminants to the Arctic resulting in increases in POP exposure of both wildlife and human populations. Exposure to vector-borne diseases and zoonoses may increase as well through range expansion and introduction of invasive species. It will be important in the future to investigate the effects of these multiple stressors on wildlife and local people to better predict the individual-level health risks. It is within this framework that One Health approaches offer promising opportunities to survey and pinpoint environmental changes that have effects on wildlife and human health.     

Prospects for incorporation of epigenetic biomarkers in human health and environmental risk assessment of chemicals

Epigenetic mechanisms have gained relevance in human health and environmental studies, due to their pivotal role in disease, gene × environment interactions and adaptation to environmental change and/or contamination. Epigenetic mechanisms are highly responsive to external stimuli and a wide range of chemicals has been shown to determine specific epigenetic patterns in several organisms. Furthermore, the mitotic/meiotic inheritance of such epigenetic marks as well as the resulting changes in gene expression and cell/organismal phenotypes has now been demonstrated. Therefore, epigenetic signatures are interesting candidates for linking environmental exposures to disease as well as informing on past exposures to stressors. Accordingly, epigenetic biomarkers could be useful tools in both prospective and retrospective risk assessment but epigenetic endpoints are currently not yet incorporated into risk assessments. Achieving a better understanding on this apparent impasse, as well as identifying routes to promote the application of epigenetic biomarkers within environmental risk assessment frameworks are the objectives of this review. We first compile evidence from human health studies supporting the use of epigenetic exposure‐associated changes as reliable biomarkers of exposure. Then, specifically focusing on environmental science, we examine the potential and challenges of developing epigenetic biomarkers for environmental fields, and discuss useful organisms and appropriate sequencing techniques to foster their development in this context. Finally, we discuss the practical incorporation of epigenetic biomarkers in the environmental risk assessment of chemicals, highlighting critical data gaps and making key recommendations for future research within a regulatory context.     

Ambient particulate matter exposure and cardiovascular diseases: a focus on progenitor and stem cells

Air pollution is a major challenge to public health. Ambient fine particulate matter (PM) is the key component for air pollution, and associated with significant mortality. The majority of the mortality following PM exposure is related to cardiovascular diseases. However, the mechanisms for the adverse effects of PM exposure on cardiovascular system remain largely unknown and under active investigation. Endothelial dysfunction or injury is considered one of the major factors that contribute to the development of cardiovascular diseases such as atherosclerosis and coronary heart disease. Endothelial progenitor cells (EPCs) play a critical role in maintaining the structural and functional integrity of vasculature. Particulate matter exposure significantly suppressed the number and function of EPCs in animals and humans. However, the mechanisms for the detrimental effects of PM on EPCs remain to be fully defined. One of the important mechanisms might be related to increased level of reactive oxygen species (ROS) and inflammation. Bone marrow (BM) is a major source of EPCs. Thus, the number and function of EPCs could be intimately associated with the population and functional status of stem cells (SCs) in the BM. Bone marrow stem cells and other SCs have the potential for cardiovascular regeneration and repair. The present review is focused on summarizing the detrimental effects of PM exposure on EPCs and SCs, and potential mechanisms including ROS formation as well as clinical implications.     

Lead Modulation of Macrophages Causes Multiorgan Detrimental Health Effects

The environmental toxicant lead (Pb) has detrimental effects on a number of organ systems, including the immune system. Pb exposure decreases host immune defenses against numerous microorganisms and cancer. Although Pb effects on humoral and cell‐mediated immunity as well as on erythrocyte, neural, and renal pathophysiology have been well documented, there are few reports regarding Pb's impact on innate immunity, which can affect multiorgan processes. This review focuses on Pb modulation of a key innate immune cell, the macrophage. The impact of Pb on macrophages in different organs, on immature versus mature macrophages, and on low versus high Pb concentrations is discussed. Pb decreases phagocytosis and chemotaxis of macrophages and affects nitric oxide production and eicosanoid metabolism in mature macrophages. Pretreatment of macrophages with Pb increases TNF‐α secretion after in vitro stimulation with lipopolysaccharide; however, Pb exposure decreases in vivo intracellular pathogen killing. More recent evidence from mouse studies indicates that even low, environmentally relevant, blood concentrations of Pb result in increased phagocytosis of erythrocytes and decreased expression of interferon‐gamma‐inducible GTPases, p65‐GBP, and p47‐IRG, which are necessary for intracellular pathogen killing. Taking into account the effects of Pb on macrophages, the review describes posited mechanisms to account for Pb‐altered health effects; Pb effects on heme levels may play a key role as well as Pb's preferential induction of helper type‐2 T (Th2) cells and M2 macrophages, which is related to oxidative stress. The discussion links old findings with new, thereby adding new insight into the effects of Pb on macrophages and the resultant compromised immunity and health.     

Global stressors and the global decline of amphibians: tipping the stress immunocompetency axis

There is a widespread consensus that the earth is experiencing a mass extinction event and at the forefront are amphibians, the most threatened of all vertebrate taxa. A recent assessment found that nearly one-third (32%, 1,856 species) of the world’s amphibian species are threatened. Amphibians have existed on the earth for over 300 million years, yet in just the last two decades there have been an alarming number of extinctions, nearly 168 species are believed to have gone extinct and at least 2,469 (43%) more have populations that are declining. Infectious diseases have been recognized as one major cause of worldwide amphibian population declines. This could be the result of the appearance of novel pathogens, or it could be that exposure to environmental stressors is increasing the susceptibility of amphibians to opportunistic pathogens. Here I review the potential effects of stressors on disease susceptibility in amphibians and relate this to disease emergence in human and other wildlife populations. I will present a series of case studies that illustrate the role of stress in disease outbreaks that have resulted in amphibian declines. First, I will examine how elevated sea-surface temperatures in the tropical Pacific since the mid-1970s have affected climate over much of the world and could be setting the stage for pathogen-mediated amphibian declines in many regions. Finally, I will discuss how the apparently rapid increase in the prevalence of amphibian limb deformities is linked to the synergistic effects of trematode infection and exposure to chemical contaminants.     

From patterns to processes and back: analysing density-dependent responses to an abiotic stressor by statistical and mechanistic modelling

Our knowledge about population-level effects of abiotic stressors is limited, largely due to lack of appropriate time-series data. To analyse interactions between an abiotic stressor and density-dependent processes, we used experimental time-series data for stage-structured populations (the blowfly Lucilia sericata) exposed to the toxicant cadmium through 20 generations. Resource limitation results in competition both in the larval and the adult stages. The toxicant has only negative effects at the organism level, but nevertheless, there were positive population-level effects. These are necessarily indirect, and indicate overcompensatory density-dependent responses. A non-parametric model (generalized additive model) was used to investigate the density-dependent structures of the demographic rates, without making assumptions about the functional forms. The estimated structures were used to develop a parametric model, with which we analysed effects of the toxicant on density-dependent and density-independent components of the stage-specific demographic rates. The parameter estimates identified both synergistic and antagonistic density-toxicant interactions. It is noteworthy that the synergistic interaction occurred together with a net positive effect of the toxicant. Hence, the effects of such interactions should be considered together with the capacity for compensatory responses. The combination of the two modelling approaches provided new insight into mechanisms for compensatory responses to abiotic stressors.     

Landscape-level toxicant exposure mediates infection impacts on wildlife populations

Anthropogenic landscape modification such as urbanization can expose wildlife to toxicants, with profound behavioural and health effects. Toxicant exposure can alter the local transmission of wildlife diseases by reducing survival or altering immune defence. However, predicting the impacts of pathogens on wildlife across their ranges is complicated by heterogeneity in toxicant exposure across the landscape, especially if toxicants alter wildlife movement from toxicant-contaminated to uncontaminated habitats. We developed a mechanistic model to explore how toxicant effects on host health and movement propensity influence range-wide pathogen transmission, and zoonotic exposure risk, as an increasing fraction of the landscape is toxicant-contaminated. When toxicant-contaminated habitat is scarce on the landscape, costs to movement and survival from toxicant exposure can trap infected animals in contaminated habitat and reduce landscape-level transmission. Increasing the proportion of contaminated habitat causes host population declines from combined effects of toxicants and infection. The onset of host declines precedes an increase in the density of infected hosts in contaminated habitat and thus may serve as an early warning of increasing potential for zoonotic spillover in urbanizing landscapes. These results highlight how sublethal effects of toxicants can determine pathogen impacts on wildlife populations that may not manifest until landscape contamination is widespread.     

Inhalation of environmental stressors & chronic inflammation: autoimmunity and neurodegeneration

Human life expectancy and welfare has decreased because of the increase in environmental stressors in the air. An environmental stressor is a natural or human-made component present in our environment that upon reaching an organic system produces a coordinated response. This response usually involves a modification of the metabolism and physiology of the system. Inhaled environmental stressors damage the airways and lung parenchyma, producing irritation, recruitment of inflammatory cells, and oxidative modification of biomolecules. Oxidatively modified biomolecules, their degradation products, and adducts with other biomolecules can reach the systemic circulation, and when found in higher concentrations than normal they are considered to be biomarkers of systemic oxidative stress and inflammation. We classify them as metabolic stressors because they are not inert compounds; indeed, they amplify the inflammatory response by inducing inflammation in the lung and other organs. Thus the lung is not only the target for environmental stressors, but it is also the source of a number of metabolic stressors that can induce and worsen pre-existing chronic inflammation. Metabolic stressors produced in the lung have a number of effects in tissues other than the lung, such as the brain, and they can also abrogate the mechanisms of immunotolerance. In this review, we discuss recent published evidence that suggests that inflammation in the lung is an important connection between air pollution and chronic inflammatory diseases such as autoimmunity and neurodegeneration, and we highlight the critical role of metabolic stressors produced in the lung. The understanding of this relationship between inhaled environmental pollutants and systemic inflammation will help us to: (1) understand the molecular mechanism of environment-associated diseases, and (2) find new biomarkers that will help us prevent the exposure of susceptible individuals and/or design novel therapies.     

Phytotechnologies – Preventing Exposures,Improving Public Health

Phytotechnologies have potential to reduce the amount or toxicity of deleterious chemicals and agents, and thereby, can reduce human exposures to hazardous substances. As such, phytotechnologies are tools for primary prevention in public health. Recent research demonstrates phytotechnologies can be uniquely tailored for effective exposure prevention in a variety of applications. In addition to exposure prevention, plants can be used as sensors to identify environmental contamination and potential exposures. In this paper, we have presented applications and research developments in a framework to illustrate how phytotechnologies can meet basic public health needs for access to clean water, air, and food. Because communities can often integrate plant-based technologies at minimal cost and with low infrastructure needs, the use of these technologies can be applied broadly to minimize potential contaminant exposure and improve environmental quality. These natural treatment systems also provide valuable ecosystem services to communities and society. In the future, integrating and coordinating phytotechnology activities with public health research will allow technology development focused on prevention of environmental exposures to toxic compounds. Hence, phytotechnologies may provide sustainable solutions to environmental exposure challenges, improving public health and potentially reducing the burden of disease.     

Mathematical model of uptake and metabolism of arsenic(III) in human hepatocytes - Incorporation of cellular antioxidant response and threshold-dependent behavior

Background  

Arsenic is an environmental pollutant, potent human toxicant, and oxidative stress agent with a multiplicity of health effects associated with both acute and chronic exposures. A semi-mechanistic cellular-level toxicokinetic (TK) model was developed in order to describe the uptake, biotransformation and clearance of arsenical species in human hepatocytes. Notable features of this model are the incorporation of arsenic-glutathione complex formation and a "switch-like" formulation to describe the antioxidant response of hepatocytes to arsenic exposure.     

What Biomonitoring Can and Cannot Tell Us about Causality in Human Health and Ecological Risk Assessments

Biomonitoring can provide exposure and effects information on various stressors (chemical or biological) that can be useful for human health and ecological risk assessments. It has been applied over the years where harmful changes in human health or the environment were observed and which may have warranted more detailed investigation. Sometimes biomonitoring programs may have been useful in determining the significance and/or cause of these harmful observations. These data can help to infer, but not confirm, causality as exemplified in classical studies conducted in humans and wildlife. However, in most cases we note that additional work was needed to provide the information necessary to support or refute causality. Today modern technology provides the ability to measure a wide variety of parameters in environmental media, plants, animals, and humans. Finding a chemical in an environmental medium or biological tissue may be helpful in understanding potential exposure (and perhaps to begin estimating hazard) to humans and ecological receptors, but mere presence does not necessarily help to establish effects or assign causality. In this article we evaluate the strengths and weaknesses, in a risk assessment context, of the use of biomonitoring data to support a determination of causality.     

The Use of Epidemiology in Risk Assessment: Challenges and Opportunities

The assessment of risk from environmental and occupational exposures incorporates and synthesizes data from a variety of scientific disciplines including toxicology and epidemiology. Epidemiological data have offered valuable contributions to the identification of human health hazards, estimation of human exposures, quantification of the exposure–response relation, and characterization of risks to specific target populations including sensitive populations. As with any scientific discipline, there are some uncertainties inherent in these data; however, the best human health risk assessments utilize all available information, characterizing strengths and limitations as appropriate. Human health risk assessors evaluating environmental and occupational exposures have raised concerns about the validity of using epidemiological data for risk assessment due to actual or perceived study limitations. This article highlights three concerns commonly raised during the development of human health risk assessments of environmental and occupational exposures: (a) error in the measurement of exposure, (b) potential confounding, and (c) the interpretation of non-linear or non-monotonic exposure–response data. These issues are often the content of scientific disagreement and debate among the human health risk assessment community, and we explore how these concerns may be contextualized, addressed, and often ameliorated.     

Seagrasses in an era of ocean warming: a review

Seagrasses are valuable sources of food and habitat for marine life and are one of Earth's most efficient carbon sinks. However, they are facing a global decline due to ocean warming and eutrophication. In the last decade, with the advent of new technology and molecular advances, there has been a dramatic increase in the number of studies focusing on the effects of ocean warming on seagrasses. Here, we provide a comprehensive review of the future of seagrasses in an era of ocean warming. We have gathered information from published studies to identify potential commonalities in the effects of warming and the responses of seagrasses across four distinct levels: molecular, biochemical/physiological, morphological/population, and ecosystem/planetary. To date, we know that although warming strongly affects seagrasses at all four levels, seagrass responses diverge amongst species, populations, and over depths. Furthermore, warming alters seagrass distribution causing massive die-offs in some seagrass populations, whilst also causing tropicalization and migration of temperate species. In this review, we evaluate the combined effects of ocean warming with other environmental stressors and emphasize the need for multiple-stressor studies to provide a deeper understanding of seagrass resilience. We conclude by discussing the most significant knowledge gaps and future directions for seagrass research.     

Acute and chronic effects of Cr(VI) on Hypsiboas pulchellus embryos and tadpoles

In the last few years there has been great concern about declines in the abundance of several species of amphibians around the world. Among amphibians, anurans have a biphasic life cycle, with aquatic tadpoles and generally terrestrial adults, and they have an extremely permeable skin, making them excellent indicators of the health of the environment. A number of different causes have been suggested for the global decline of anurans, the pollution of their habitat by chemical stressors being considered one of the major factors. Among chemical stressors, heavy metals are known for their high toxicity at very low concentrations. This study assessed short- (96 h, 'acute') and long-term (1272 h, 'chronic') exposure to Cr(VI) at lethal (3 to 90 mg 1(-1)) and sublethal concentrations (0.001 to 12 mg 1(-1)) on Hypsiboaspulchellus (previously called Hyla pulchella; see Faivovich et al. 2005) tadpoles (Fam. Hylidae) from central eastern Argentina. Fertilized eggs collected from a clean pond near La Plata (Buenos Aires Province) were used for acute and chronic toxicity testing. Assays were done under controlled laboratory conditions. Results of chronic exposure were used to assess the effect of factors such as toxicant concentration and age of organisms at the beginning of exposure on the response variables (growth, development and survival until metamorphosis). Results indicated a higher sensitivity to Cr(VI) of individuals first exposed as tadpoles than those first exposed as embryos during acute and chronic exposure. Exposure to the highest sublethal concentrations (6 to 12 mg 1(-1)) of the toxicant showed early inhibitory effects on growth of all treated organisms compensated at longer exposure periods with an increase in the growth rate compared to the control groups.     

MicroRNAs as biomarkers of harmful environmental and occupational exposures: a systematic review

Abstract

Environmental exposure is a growing public health burden associated with several negative health effects. An estimated 4.2 million deaths occur each year from ambient air pollution alone. Biomarkers that reflect specific exposures have the potential to measure the real integrated internal dose from all routes of complex environmental exposure. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, have been studied as biomarkers in various diseases and have also shown potential as environmental exposure biomarkers. Here, we review the available human epidemiological and experimental evidence of miRNA expression changes in response to specific environmental exposures including airborne particulate matter. In doing so, we establish that miRNA exposure biomarker development remains in its infancy and future studies will need to carefully consider biological and analytical ‘design rules’ in order to facilitate clinical translation.     

Telomere dynamics may link stress exposure and ageing across generations

Although exposure to stressors is known to increase disease susceptibility and accelerate ageing, evidence is accumulating that these effects can span more than one generation. Stressors experienced by parents have been reported to negatively influence the longevity of their offspring and even grand offspring. The mechanisms underlying these long-term, cross-generational effects are still poorly understood, but we argue here that telomere dynamics are likely to play an important role. In this review, we begin by surveying the current connections between stress and telomere dynamics. We then lay out the evidence that exposure to stressors in the parental generation influences telomere dynamics in offspring and potentially subsequent generations. We focus on evidence in mammalian and avian studies and highlight several promising areas where our understanding is incomplete and future investigations are critically needed. Understanding the mechanisms that link stress exposure across generations requires interdisciplinary studies and is essential to both the biomedical community seeking to understand how early adversity impacts health span and evolutionary ecologists interested in how changing environmental conditions are likely to influence age-structured population dynamics.     

Biochemical evidence on the potential role of methyl mercury in hepatic glucose metabolism through inflammatory signaling and free radical pathways

Methylmercury (MeHg) is an extremely important environmental toxicant posing serious health risks to human health and a big source of environmental pollutant. Numerous evidence available showing a link between nervous system toxicity and MeHg exposure. Other forms of mercury are reason of metabolic toxic effects and alteration of DNA in the human body. The sources of exposure could be occupational or other environmental settings. In the present study MeHg was orally gavaged to mice, at doses of 2.5, 5, and 10 mg/kg for 4 weeks. Fasting hyperglycemia, activity of hepatic phoshphoenolpyruvate carboxykinase and glucose 6-phoshphate were reported high as compared to control group. Inflammatory markers like, tumor necrosis factor α, the actual end product of inflammatory mediators’ cascade pathway was also raised in comparison to control group. Hyperinsulinemia observed in serum showed clear understanding of mercury induced insulin resistance. Moreover, tissue damage due to increased oxidative stress markers like, hepatic lipid peroxidation, 8-deoxygunosine, reactive oxygen species, and carbonyl groups was significantly higher as compared to control group. MeHg caused a significant reduction in antioxidant markers like ferric reducing antioxidant power and total thiol molecules. The present study highlighted that activity of key enzymes involved in glucose metabolism is changed, owing to MeHg induced toxicity in the liver. Induction of similar toxic effects assumed to be stimulated by the production of high quantity free radicals.