Environmental Epigenetics最新文献

DNA methylation is an important epigenetic modification that is widely conserved across animal genomes. It is widely accepted that DNA methylation patterns can change in a context-dependent manner, including in response to changing environmental parameters. However, this phenomenon has not been analyzed in animal livestock yet, where it holds major potential for biomarker development. Building on the previous identification of population-specific DNA methylation in clonal marbled crayfish, we have now generated numerous base-resolution methylomes to analyze location-specific DNA methylation patterns. We also describe the time-dependent conversion of epigenetic signatures upon transfer from one environment to another. We further demonstrate production system-specific methylation signatures in shrimp, river-specific signatures in salmon and farm-specific signatures in chicken. Together, our findings provide a detailed resource for epigenetic variation in animal livestock and suggest the possibility for origin tracing of animal products by epigenetic fingerprinting.

Human epidemiological studies reveal that dietary and environmental alterations influence the health of the offspring and that the effect is not limited to the F1 or F2 generations. Non-Mendelian transgenerational inheritance of traits in response to environmental stimuli has been confirmed in non-mammalian organisms including plants and worms and are shown to be epigenetically mediated. However, transgenerational inheritance beyond the F2 generation remains controversial in mammals. Our lab previously discovered that the treatment of rodents (rats and mice) with folic acid significantly enhances the regeneration of injured axons following spinal cord injury in vivo and in vitro, and the effect is mediated by DNA methylation. The potential heritability of DNA methylation prompted us to investigate the following question: Is the enhanced axonal regeneration phenotype inherited transgenerationally without exposure to folic acid supplementation in the intervening generations? In the present review, we condense our findings showing that a beneficial trait (i.e., enhanced axonal regeneration after spinal cord injury) and accompanying molecular alterations (i.e., DNA methylation), triggered by an environmental exposure (i.e., folic acid supplementation) to F0 animals only, are inherited transgenerationally and beyond the F3 generation.

Developmental robustness represents the ability of an organism to resist phenotypic variations despite environmental insults and inherent genetic variations. Derailment of developmental robustness leads to phenotypic variations that can get fixed in a population for many generations. Environmental pollution is a significant worldwide problem with detrimental consequences of human development. Understanding the genetic basis for how pollutants affect human development is critical for developing interventional therapies. Here, we report that environmental stress induced by hexavalent chromium, Cr(VI), a potent industrial pollutant, compromises developmental robustness, leading to phenotypic variations in the progeny. These phenotypic variations arise due to epigenetic instability and transposon activation in the somatic tissues of the progeny rather than novel genetic mutations and can be reduced by increasing the dosage of Piwi - a Piwi-interacting RNA-binding protein, in the ovary of the exposed mother. Significantly, the derailment of developmental robustness by Cr(VI) exposure leads to tumors in the progeny, and the predisposition to develop tumors is fixed in the population for at least three generations. Thus, we show for the first time that environmental pollution can derail developmental robustness and predispose the progeny of the exposed population to develop phenotypic variations and tumors.

Environmental effects on gene expression and offspring development can be mediated by epigenetic modifications. It is well established that maternal diet influences DNA methylation patterns and phenotypes in the offspring; however, the epigenetic effects of paternal diet on developing offspring warrants further investigation. Here, we examined how a prepubertal methionine-enriched paternal diet affected sperm DNA methylation and its subsequent effects on embryo gene expression. Three treatment and three control rams were bred to seven ewes, and blastocysts were flushed for RNA extraction. Semen was collected from all rams and submitted for reduced representation bisulfite sequencing analysis. In total, 166 differentially methylated cytosines were identified in the sperm from treatment versus control rams. Nine genes were found to be differentially expressed in embryos produced from treatment versus control rams, and seven differentially methylated cytosines in the sperm were found to be highly correlated with gene expression in the embryos. Our results demonstrate that sperm methylation differences induced by diet may influence fetal programming.

This review article provides a framework for the use of deoxyribonucleic acid (DNA) methylation (DNAm) biomarkers to study the biological embedding of socioeconomic position (SEP) and summarizes the latest developments in the area. It presents the emerging literature showing associations between individual- and neighborhood-level SEP exposures and DNAm across the life course. In contrast to questionnaire-based methods of assessing SEP, we suggest that DNAm biomarkers may offer an accessible metric to study questions about SEP and health outcomes, acting as a personal dosimeter of exposure. However, further work remains in standardizing SEP measures across studies and evaluating consistency across domains, tissue types, and time periods. Meta-analyses of epigenetic associations with SEP are offered as one approach to confirm the replication of DNAm loci across studies. The development of DNAm biomarkers of SEP would provide a method for examining its impact on health outcomes in a more robust way, increasing the rigor of epidemiological studies.

Epidural anesthesia is an effective pain relief modality, widely used for labor analgesia. Childhood asthma is one of the commonest chronic medical illnesses in the USA which places a significant burden on the health-care system. We recently demonstrated a negative association between the duration of epidural anesthesia and the development of childhood asthma; however, the underlying molecular mechanisms still remain unclear. In this study of 127 mother-child pairs comprised of 75 Non-Hispanic Black (NHB) and 52 Non-Hispanic White (NHW) from the Newborn Epigenetic Study, we tested the hypothesis that umbilical cord blood DNA methylation mediates the association between the duration of exposure to epidural anesthesia at delivery and the development of childhood asthma and whether this differed by race/ethnicity. In the mother-child pairs of NHB ancestry, the duration of exposure to epidural anesthesia was associated with a marginally lower risk of asthma (odds ratio = 0.88, 95% confidence interval = 0.76-1.01) for each 1-h increase in exposure to epidural anesthesia. Of the 20 CpGs in the NHB population showing the strongest mediation effect, 50% demonstrated an average mediation proportion of 52%, with directional consistency of direct and indirect effects. These top 20 CpGs mapped to 21 genes enriched for pathways engaged in antigen processing, antigen presentation, protein ubiquitination and regulatory networks related to the Major Histocompatibility Complex (MHC) class I complex and Nuclear Factor Kappa-B (NFkB) complex. Our findings suggest that DNA methylation in immune-related pathways contributes to the effects of the duration of exposure to epidural anesthesia on childhood asthma risk in NHB offspring.

As prenatal and community cannabis exposures have recently been linked with congenital heart disease (CHD), it was of interest to explore these associations in Europe in a causal framework and space-time context. Congenital anomaly data from Eurocat, drug-use data from the European Monitoring Centre for Drugs and Drug Addiction, and income from the World Bank. Countries with rising daily cannabis use had in general higher congenital anomaly rates over time than those without (time: status interaction: β-Est. = 0.0267, P = 0.0059). At inverse probability-weighted panel regression, cannabis terms were positive and significant for CHD, severe CHD, atrial septal defect, ventricular septal defect, atrioventricular septal defect, patent ductus arteriosus, tetralogy of Fallot, vascular disruptions, double outlet right ventricle, transposition of the great vessels, hypoplastic right heart, and mitral valve anomalies from 1.75 × 10^-19, 4.20 × 10^-11, <2.2 × 10^-16, <2.2 × 10^-16, 1.58 × 10^-12, 4.30 × 10^-9, 4.36 × 10^-16, 3.50 × 10^-8, 5.35 × 10^-12, <2.2 × 10^-16, 5.65 × 10^-5 and 6.06 × 10^-10. At spatial regression, terms including cannabis were positive and significant for this same list of anomalies from 0.0038, 1.05 × 10^-10, 0.0215, 8.94 × 10^-6, 1.23 × 10^-5, 2.05 × 10^-5, 1.07 × 10^-6, 8.77 × 10^-5, 9.11 × 10^-6, 0.0001, 3.10 × 10^-7 and 2.17 × 10^-7. 92.6% and 75.2% of 149 E-value estimates and minimum E-values were in high zone >9; 100.0% and 98.7% >1.25. Data show many congenital cardiac anomalies exhibit strong bivariate relationships with metrics of cannabis exposure. Causal inferential modelling for the twelve anomalies selected demonstrated convincing evidence of robust relationships to cannabis which survived adjustment and fulfilled epidemiological criteria for causal relationships. Space-time regression was similarly confirmatory. Epigenomic pathways constitute viable potential mechanisms. Given exponential genotoxic dose-response effects, careful and astute control of cannabinoid penetration is indicated.