Environmental Epigenetics最新文献

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.

Breast cancer (BC) is the commonest human cancer and its incidence (BC incidence, BCI) is rising worldwide. Whilst both tobacco and alcohol have been linked to BCI genotoxic cannabinoids have not been investigated. Age-adjusted state-based BCI 2003-2017 was taken from the Surveillance Epidemiology and End Results database of the Centers for Disease Control. Drug use from the National Survey of Drug Use and Health, response rate 74.1%. Median age, median household income and ethnicity were from US census. Inverse probability weighted (ipw) multivariable regression conducted in R. In bivariate analysis BCI was shown to be significantly linked with rising cannabis exposure {β-est. = 3.93 [95% confidence interval 2.99, 4.87], P = 1.10 × 10^-15}. At 8 years lag cigarettes:cannabis [β-est. = 2660 (2150.4, 3169.3), P = 4.60 × 10^-22] and cannabis:alcoholism [β-est. = 7010 (5461.6, 8558.4), P = 1.80 × 10^-17] were significant in ipw-panel regression. Terms including cannabidiol [CBD; β-est. = 16.16 (0.39, 31.93), P = 0.446] and cannabigerol [CBG; β-est. = 6.23 (2.06, 10.39), P = 0.0034] were significant in spatiotemporal models lagged 1:2 years, respectively. Cannabis-liberal paradigms had higher BCI [67.50 ± 0.26 v. 65.19 ± 0.21/100 000 (mean ± SEM), P = 1.87 × 10^-11; β-est. = 2.31 (1.65, 2.96), P = 9.09 × 10^-12]. 55/58 expected values >1.25 and 13/58 >100. Abortion was independently and causally significant in space-time models. Data show that exposure to cannabis and the cannabinoids Δ9-tetrahydrocannabinol, CBD, CBG and alcoholism fulfil quantitative causal criteria for BCI across space and time. Findings are robust to adjustment for age and several known sociodemographic, socio-economic and hormonal risk factors and establish cannabinoids as an additional risk factor class for breast carcinogenesis. BCI is higher under cannabis-liberal legal paradigms.