Environmental Epigenetics最新文献

Tossed about by the tides of history, the inheritance of acquired characteristics has found a safe harbor at last in the rapidly expanding field of epigenetics. The slow pace of genetic variation and high opportunity cost associated with maintaining a diverse genetic pool are well-matched by the flexibility of epigenetic traits, which can enable low-cost exploration of phenotypic space and reactive tuning to environmental pressures. Aiding in the generation of a phenotypically plastic population, epigenetic mechanisms often provide a hotbed of innovation for countering environmental pressures, while the potential for genetic fixation can lead to strong epigenetic-genetic evolutionary synergy. At the level of cells and cellular populations, we begin this review by exploring the breadth of mechanisms for the storage and intergenerational transmission of epigenetic information, followed by a brief review of common and exotic epigenetically regulated phenotypes. We conclude by offering an in-depth coverage of recent papers centered around two critical issues: the evolvability of epigenetic traits through Baldwinian adaptive phenotypic plasticity and the potential for synergy between epigenetic and genetic evolution.

Despite still being a matter of debate, there is growing evidence that pollutant-induced epigenetic changes can be propagated across generations. Whereas such modifications could have long-lasting effects on organisms and even on population, environmentally relevant data from long-term exposure combined with follow-up through multiple generations remain scarce for non-mammalian species. We performed a transgenerational experiment comprising four successive generations of zebrafish. Only fish from the first generation were exposed to an environmentally realistic concentration of cadmium (Cd). Using a whole methylome analysis, we first identified the DNA regions that were differentially methylated in response to Cd exposure and common to fish of the first two generations. Among them, we then focused our investigations on the exon 3 (ex3) of the cep19 gene. We indeed recorded transgenerational growth disorders in Cd-exposed fish, and a mutation in this exon is known to cause morbid obesity in mammals. Its methylation level was thus determined in zebrafish from all the four generations by means of a targeted and base resolution method. We observed a transgenerational inheritance of Cd-induced DNA methylation changes up to the fourth generation. However, these changes were closely associated with genetic variations, mainly a single nucleotide polymorphism. This single nucleotide polymorphism was itself at the origin of the creation or deletion of a methylation site and deeply impacted the methylation level of neighboring methylation sites. Cd-induced epigenetic changes were associated with different mRNA transcripts and an improved condition of Cd fish. Our results emphasize a tight relationship between genetic and epigenetic mechanisms and suggest that their interplay and pre-existing diversity can allow rapid adaptation to anthropogenic environmental changes.

Exposure to environmental pollution and the increase in the incidence of multifactorial diseases in the population have become health problems for industrialized countries. In this context, the question of the health impact of exposure to these pollutants is not clearly identified in the low-dose range. This article looks at this problem using the example of preclinical studies of the effects of chronic low-dose exposure to uranium in rats. These studies demonstrate the value of molecular screening analyses (omics) and multimodal integrative approaches, of which the extreme sensitivity and breadth of observation spectrum make it possible to observe all the biological processes affected and the mechanisms of action triggered at the molecular level by exposure to low doses. They also show the value of these analytical approaches for finding diagnostic biomarkers or indicators of prognosis, which can be necessary to evaluate a risk. Finally, the results of these studies raise the question of the health risk caused by epigenomic deregulations occurring during critical developmental phases and their potential contribution to the development of chronic diseases that are metabolic in origin or to the development of certain cancer liable in the long term to affect the exposed adult and possibly its progeny.

Epigenetic inheritance has emerged as a new research discipline that aims to study the mechanisms underlying the transmission of acquired traits across generations. Such transmission is well established in plants and invertebrates but remains not well characterized and understood in mammals. Important questions are how life experiences and environmental factors induce phenotypic changes that are passed to the offspring of exposed individuals, sometimes across several successive generations, what is the contribution of germ cells and what are the consequences for health and disease. These questions were recently discussed at the symposium Epigenetic Inheritance: Impact for Biology and Society organized every 2 years in Zürich, Switzerland. This review provides a summary of the research presented during the symposium and discusses current important questions, perspectives and challenges for the field in the future.

Despite substantial strides in diagnosis and treatment, cardiovascular diseases (CVDs) continue to represent the leading cause of death in the USA and around the world, resulting in significant morbidity and loss of productive years of life. It is increasingly evident that environmental exposures during early development can influence CVD risk across the life course. CVDs exhibit marked sexual dimorphism, but how sex interacts with environmental exposures to affect cardiovascular health is a critical and understudied area of environmental health. Emerging evidence suggests that developmental exposures may have multi- and transgenerational effects on cardiovascular health, with potential sex differences; however, further research in this important area is urgently needed. Lead (Pb), phthalate plasticizers, and perfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants with numerous adverse human health effects. Notably, recent evidence suggests that developmental exposure to each of these toxicants has sex-specific effects on cardiovascular outcomes, but the underlying mechanisms, and their effects on future generations, require further investigation. This review article will highlight the role for the developmental environment in influencing cardiovascular health across generations, with a particular emphasis on sex differences and epigenetic mechanisms. In particular, we will focus on the current evidence for adverse multi and transgenerational effects of developmental exposures to Pb, phthalates, and PFAS and highlight areas where further research is needed.

Life experiences and environmental conditions in childhood can change the physiology and behaviour of exposed individuals and, in some cases, of their offspring. In rodent models, stress/trauma, poor diet, and endocrine disruptors in a parent have been shown to cause phenotypes in the direct progeny, suggesting intergenerational inheritance. A few models also examined transmission to further offspring and suggested transgenerational inheritance, but such multigenerational inheritance is not well characterized. Our previous work on a mouse model of early postnatal stress showed that behaviour and metabolism are altered in the offspring of exposed males up to the 4th generation in the patriline and up to the 2nd generation in the matriline. The present study examined if symptoms can be transmitted beyond the 4th generation in the patriline. Analyses of the 5th and 6th generations of mice revealed that altered risk-taking and glucose regulation caused by postnatal stress are still manifested in the 5th generation but are attenuated in the 6th generation. Some of the symptoms are expressed in both males and females, but some are sex-dependent and sometimes opposite. These results indicate that postnatal trauma can affect behaviour and metabolism over many generations, suggesting epigenetic mechanisms of transmission.

Acute environmental stressors such as short-term exposure to pollutants can have lasting effects on organisms, potentially impacting future generations. Parental exposure to toxicants can result in changes to the epigenome (e.g., DNA methylation) that are passed down to subsequent, unexposed generations. However, it is difficult to gauge the cumulative population-scale impacts of epigenetic effects from laboratory experiments alone. Here, we developed a size- and age-structured delay-coordinate population model to evaluate the long-term consequences of epigenetic modifications on population sustainability. The model emulated changes in growth, mortality, and fecundity in the F0, F1, and F2 generations observed in experiments in which larval Menidia beryllina were exposed to environmentally relevant concentrations of bifenthrin (Bif), ethinylestradiol (EE2), levonorgestrel (LV), or trenbolone (TB) in the parent generation (F0) and reared in clean water up to the F2 generation. Our analysis suggests potentially dramatic population-level effects of repeated, chronic exposures of early-life stage fish that are not captured by models not accounting for those effects. Simulated exposures led to substantial declines in population abundance (LV and Bif) or near-extinction (EE2 and TB) with the exact trajectory and timeline of population decline dependent on the combination of F0, F1, and F2 effects produced by each compound. Even acute one-time exposures of each compound led to declines and recovery over multiple years due to lagged epigenetic effects. These results demonstrate the potential for environmentally relevant concentrations of commonly used compounds to impact the population dynamics and sustainability of an ecologically relevant species and model organism.

Although the effects of lead, mercury, manganese, and copper on individual disease processes are well understood, estimating the health effects of long-term exposure to these metals at the low concentrations often observed in the general population is difficult. In addition, the health effects of joint exposure to multiple metals are difficult to estimate. Biological aging refers to the integrative progression of multiple physiologic and molecular changes that make individuals more at risk of disease. Biomarkers of biological aging may be useful to estimate the population-level effects of metal exposure prior to the development of disease in the population. We used data from 290 participants in the Detroit Neighborhood Health Study to estimate the effect of serum lead, mercury, manganese, and copper on three DNA methylation-based biomarkers of biological aging (Horvath Age, PhenoAge, and GrimAge). We used mixed models and Bayesian kernel machine regression and controlled for participant sex, race, ethnicity, cigarette use, income, educational attainment, and block group poverty. We observed consistently positive estimates of the effects between lead and GrimAge acceleration and mercury and PhenoAge acceleration. In contrast, we observed consistently negative associations between manganese and PhenoAge acceleration and mercury and Horvath Age acceleration. We also observed curvilinear relationships between copper and both PhenoAge and GrimAge acceleration. Increasing total exposure to the observed mixture of metals was associated with increased PhenoAge and GrimAge acceleration and decreased Horvath Age acceleration. These findings indicate that an increase in serum lead or mercury from the 25th to 75th percentile is associated with a ∼0.25-year increase in two epigenetic markers of all-cause mortality in a population of adults in Detroit, Michigan. While few of the findings were statistically significant, their consistency and novelty warrant interest.