Current Environmental Health Reports最新文献

Purpose of review: Review human literature on the relationship between prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and epigenetic modifications in infants, children, and adolescents < 18 years of age.

Recent findings: Eleven studies were identified, with study populations located in the U.S., Taiwan, Japan, and the Kingdom of Denmark. Many studies (n = 5) were cross-sectional, with PFAS exposure and epigenetic outcomes measured in the same tissue collected at delivery via cord blood or dried newborn blood spots. The other six studies were prospective, with prenatal PFAS measured on maternal blood during pregnancy and DNA methylation (DNAm) assessed in cord blood and childhood peripheral leukocytes (n = 1 study). Epigenetic marks of interest included global DNAm measures (LINE-1, Alu, and an ELISA-based method), candidate genes (IFG2, H19, and MEST), and epigenome-wide DNA methylation via array-based methods (Infinium 450 K and EPIC). Two studies using array-based methods employed discovery and validation paradigms, in which a small subset of loci (n = 6 and n = 4) were replicated in the discovery population. One site (TNXB) was a hit in two independent studies. Collectively, loci associated with PFAS were in regions involved in growth and development, lipid metabolism, and nutrient metabolism. There is moderate human evidence supporting associations of prenatal PFAS exposure on DNAm at birth, with one study suggesting sustained effects into childhood. Future studies are warranted to link PFAS-associated DNAm to health outcomes, as well as to investigate the role of other epigenetic marks such as hydroxymethylation, miRNA expression, and histone modifications.

Purpose of review: The Mediterranean basin is highly vulnerable to climate change. This study is aimed at quantifying the risk of mortality associated with exposure to high ambient temperature in the Mediterranean basin in the general population and in vulnerable sub-populations.

Recent findings: We retrieved effect estimates from studies linking temperature and mortality in the Mediterranean basin, between 2000 and 2021. In a meta-analysis of 16 studies, we found an increased risk of all-cause mortality due to ambient heat/high temperature exposure in the Mediterranean basin, with a pooled RR of 1.035 (95%CI 1.028-1.041) per 1 °C increase in temperature above local thresholds (I² = 79%). Risk was highest for respiratory mortality (RR = 1.063, 95% CI 1.052-1.074) and cardiovascular mortality (RR = 1.046, 95% CI 1.036-1.057). Hot ambient temperatures increase the mortality risk across the Mediterranean basin. Further studies, especially in North African, Asian Mediterranean, and eastern European countries, are needed to bolster regional preparedness against future heat-related health burdens.

Purpose of review: We discuss how epidemiologic studies have used observational data to estimate the effects of potential interventions on early-life environmental exposures. We summarize the value of posing questions about interventions, how a group of techniques known as "g-methods" can provide advantages for estimating intervention effects, and how investigators have grappled with the strong assumptions required for causal inference.

Recent findings: We identified nine studies that estimated health effects of hypothetical interventions on early-life environmental exposures. Of these, six examined air pollution. Interventions evaluated by these studies included setting exposure levels at a specific value, shifting exposure distributions, and limiting exposure levels to less than a threshold value. Only one study linked exposure contrasts to a specific intervention on an exposure source, however. There is growing interest in estimating intervention effects of early-life environmental exposures, in part because intervention effects are directly related to possible public health actions. Future studies can build on existing work by linking research questions to specific hypothetical interventions that could reduce exposure levels. We discuss how framing questions around interventions can help overcome some of the barriers to causal inference and how advances related to machine learning may strengthen studies by sidestepping the overly restrictive assumptions of parametric regression models. By leveraging advancements in causal inference and exposure science, an intervention framework for environmental epidemiology can guide actionable solutions to improve children's environmental health.

Purpose of review: This review aims to better understand the utility of machine learning algorithms for predicting spatial patterns of contaminants in the United States (U.S.) drinking water.

Recent findings: We found 27 U.S. drinking water studies in the past ten years that used machine learning algorithms to predict water quality. Most studies (42%) developed random forest classification models for groundwater. Continuous models show low predictive power, suggesting that larger datasets and additional predictors are needed. Categorical/classification models for arsenic and nitrate that predict exceedances of pollution thresholds are most common in the literature because of good national scale data coverage and priority as environmental health concerns. Most groundwater data used to develop models were obtained from the United States Geological Survey (USGS) National Water Information System (NWIS). Predictors were similar across contaminants but challenges are posed by the lack of a standard methodology for imputation, pre-processing, and differing availability of data across regions. We reviewed 27 articles that focused on seven drinking water contaminants. Good performance metrics were reported for binary models that classified chemical concentrations above a threshold value by finding significant predictors. Classification models are especially useful for assisting in the design of sampling efforts by identifying high-risk areas. Only a few studies have developed continuous models and obtaining good predictive performance for such models is still challenging. Improving continuous models is important for potential future use in epidemiological studies to supplement data gaps in exposure assessments for drinking water contaminants. While significant progress has been made over the past decade, methodological advances are still needed for selecting appropriate model performance metrics and accounting for spatial autocorrelations in data. Finally, improved infrastructure for code and data sharing would spearhead more rapid advances in machine-learning models for drinking water quality.

Purpose of review: To summarize recent literature relating early-life environmental exposures on DNA methylation in the placenta, to identify how variation in placental methylation is regulated in an exposure-specific manner, and to encourage additional work in this area.

Recent findings: Multiple studies have evaluated associations between prenatal environmental exposures and placental methylation in both gene-specific and epigenome-wide frameworks. Specific exposures lead to unique variability in methylation, and cross-exposure assessments have uncovered certain genes that demonstrate consistency in differential placental methylation. Exposure studies that assess methylation effects in a trimester-specific approach tend to find larger effects during the 1st trimester exposure. Earlier studies have more targeted gene-specific approaches to methylation, while later studies have shifted towards epigenome-wide, array-based approaches. Studies focusing on exposures such as air pollution, maternal smoking, environmental contaminants, and trace metals appear to be more abundant, while studies of socioeconomic adversity and circadian disruption are scarce but demonstrate remarkable effects. Understanding the impacts of early-life environmental exposures on placental methylation is critical to establishing the link between the maternal environment, epigenetic variation, and long-term health. Future studies into this field should incorporate repeated measures of exposure throughout pregnancy, in order to determine the critical windows in which placental methylation is most heavily affected. Additionally, the use of methylation-based scores and sequencing technology could provide important insights into epigenetic gestational age and uncovering more genomic regions where methylation is affected. Studies examining the impact of other exposures on methylation, including pesticides, alcohol, and other chemicals are also warranted.

Purpose of review: Racial inequities in air pollution exposure have been documented. There is also interest in documenting the modifying role of race in the link between air pollution and health. However, the empirical literature in this area has yielded mixed results with potentially unclear policy implications. We critically evaluate recent empirical papers on the interactive association between race and air pollution exposure on adult mortality in the USA as a case study of the race, pollution, and health literature. Specifically, we evaluate these studies for the conceptualization and discussion of race and the use of race variables that may contribute to the ambiguous results and policy implications both in this specific literature and in the broader literature.

Recent findings: We evaluate ten empirical studies from 2016 to 2022 on the modifying role of race in the association between short- and long-term PM_2.5 exposure and specific types of adult mortality (all cause, non-accidental, and heart or cardiovascular diseases) in the USA. In addition to comparing and contrasting the empirical results, we focus our review on the conceptualization, measurement, modeling, and discussion of race and the race variables. Overall, the results indicate no consistent role of race in the association between PM_2.5 exposure and mortality. Moreover, conceptualization and discussion of race was often brief and incomplete, even when the empirical results were unexpected or counterintuitive. To build on recent discussions in the epidemiology and environmental epidemiology literature more specifically, we provide a detailed discussion of the meaning of race, the race variables, and the cultural and structural racism that some argue are proxied by race variables. We use theoretical scholarship from the humanities and social sciences along with empirical work from the environmental literature to provide recommendations for future research that can provide an evidence base to inform both social and environmental policy.

PURPOSE OF REVIEW: The epigenome modulates gene expression in response to environmental stimuli. Modifications to the epigenome are potentially reversible, making them a promising therapeutic approach to mitigate environmental exposure effects on human health. This review details currently available genome and epigenome editing technologies and highlights ncRNA, including piRNA, as potential tools for targeted epigenome editing. RECENT FINDINGS: Zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats (CRISPR) associated nuclease (CRISPR/Cas) research has significantly advanced genome editing technology, with broad promise in genetic research and targeted therapies. Initial epigenome-directed therapies relied on global modification and suffered from limited specificity. Adapted from current genome editing tools, zinc finger protein (ZFP), TALE, and CRISPR/nuclease-deactivated Cas (dCas) systems now confer locus-specific epigenome editing, with promising applicability in the field of environmental health sciences. However, high incidence of off-target effects and time taken for screening limit their use. FUTURE DEVELOPMENT: ncRNA serve as a versatile biomarker with well-characterized regulatory mechanisms that can easily be adapted to edit the epigenome. For instance, the transposon silencing mechanism of germline PIWI-interacting RNAs (piRNA) could be engineered to specifically methylate a given gene, overcoming pitfalls of current global modifiers. Future developments in epigenome editing technologies will inform risk assessment through mechanistic investigation and serve as potential modes of intervention to mitigate environmentally induced adverse health outcomes later in life.

Purpose of review: Mitochondria play various roles that are important for cell function and survival; therefore, significant mitochondrial dysfunction may have chronic consequences that extend beyond the cell. Mitochondria are already susceptible to damage, which may be exacerbated by environmental exposures. Therefore, the aim of this review is to summarize the recent literature (2012-2022) looking at the effects of six ubiquitous classes of compounds on mitochondrial dysfunction in human populations.

Recent findings: The literature suggests that there are a number of biomarkers that are commonly used to identify mitochondrial dysfunction, each with certain advantages and limitations. Classes of environmental toxicants such as polycyclic aromatic hydrocarbons, air pollutants, heavy metals, endocrine-disrupting compounds, pesticides, and nanomaterials can damage the mitochondria in varied ways, with changes in mtDNA copy number and measures of oxidative damage the most commonly measured in human populations. Other significant biomarkers include changes in mitochondrial membrane potential, calcium levels, and ATP levels. This review identifies the biomarkers that are commonly used to characterize mitochondrial dysfunction but suggests that emerging mitochondrial biomarkers, such as cell-free mitochondria and blood cardiolipin levels, may provide greater insight into the impacts of exposures on mitochondrial function. This review identifies that the mtDNA copy number and measures of oxidative damage are commonly used to characterize mitochondrial dysfunction, but suggests using novel approaches in addition to well-characterized ones to create standardized protocols. We identified a dearth of studies on mitochondrial dysfunction in human populations exposed to metals, endocrine-disrupting chemicals, pesticides, and nanoparticles as a gap in knowledge that needs attention.

Purpose of the review: Exposure to essential and non-essential metals is widespread. Metals exposure is linked to epigenetic, particularly DNA methylation, differences. The strength of evidence with respect to the metal exposure type, timing, and level, as well as the DNA methylation association magnitude, and reproducibility are not clear. Focusing on the most recent 3 years, we reviewed the human epidemiologic evidence (n = 26 studies) and the toxicologic animal model evidence (n = 18 studies) for associations between metals exposure and DNA methylation.

Recent findings: In humans, the greatest number of studies focused on lead exposure, followed by studies examining cadmium and arsenic. Approximately half of studies considered metals exposure during the in utero period and measured DNA methylation with the genome-wide Illumina arrays in newborn blood or placenta. Few studies performed formal replication testing or meta-analyses. Toxicology studies of metals and epigenetics had diversity in model systems (mice, rats, drosophila, tilapia, and zebrafish were represented), high heterogeneity of tissues used for DNA methylation measure (liver, testis, ovary, heart, blood, brain, muscle, lung, kidney, whole embryo), and a variety of technologies used for DNA methylation assessment (global, gene specific, genome-wide). The most common metals tested in toxicologic studies were lead and cadmium. Together, the recent studies reviewed provide the strongest evidence for DNA methylation signatures with prenatal metals exposures. There is also mounting epidemiologic evidence supporting lead, arsenic, and cadmium exposures with DNA methylation signatures in adults. The field of metals and DNA methylation is strengthened by the inclusion of both epidemiology and toxicology approaches, and further advancements can be made by coordinating efforts or integrating analyses across studies. Future advances in understanding the molecular basis of sequence specific epigenetic responses to metals exposures, methods for handling exposure mixtures in a genome-wide analytic framework, and pipelines to facilitate collaborative testing will continue to advance the field.

Purpose of review: Exposure to endocrine disrupting chemicals through personal care products (PCPs) is widespread and may disrupt hormone-sensitive endpoints, such as timing of puberty. Given the well-documented (and ongoing) decline in age at menarche in many populations, we conducted a systematic review of the epidemiological literature on exposure to chemicals commonly found in PCPs (including certain phthalates, phenols, and parabens) in relation to girls' pubertal development.

Recent findings: The preponderance of research on this topic has examined phthalate exposures with the strongest evidence indicating that prenatal monoethyl phthalate (MEP) concentrations may be associated with slightly earlier timing of puberty, including age at menarche. Findings examining peri-pubertal phthalate exposures and pubertal outcomes were less consistent as were studies of prenatal and peri-pubertal phenol exposures. Very few studies had examined parabens in relation to girls' pubertal development. Common study limitations included potential exposure misclassification related to use of spot samples and/or mistimed biomarker assessment with respect to the outcomes. The role of body size as a mediator in these relationships remains unresolved. Overall, evidence of associations between chemical exposures in PCPs and girls' pubertal development was conflicting. When associations were observed, effect sizes were small. Nevertheless, given the many environmental, social, and behavioral factors in the modern environment that may act synergistically to accelerate timing of puberty, even marginal changes may be cause for concern, with implications for cancer risk, mental health, and cardiometabolic disease in later life.