Environmental Epigenetics最新文献

Environmental stressors, such as benzo[a]pyrene (BaP), have been repeatedly associated with developmental bone defects in offspring after parental exposures. Chemical modifications along the histone 3 protein (H3) and histone 4 protein (H4) tails are crucial for osteoblast differentiation. Therefore, H3K4me3, H3K9me3, H3K27me3, H3K27ac, and H4K5ac/K8ac/K12ac have been assessed by immunofluorescence. F1 adults from a transgenic twist:dsred/col10a1:gfp medaka (Oryzias latipes) strain with/without parental BaP exposure were assessed to yield novel data on the histone code of osteoblasts and allow quantification of parental environmental pollutant exposure's interference with chromatin structure regulation. In twist ⁺ cells, BaP exposure significantly reduced H3K9me3 marks in both male and female fish. Significant reductions of H3K9me3 and H4K5ac/K8ac/K12ac were observed in col10a1 ⁺ cells of male fish with parental BaP exposure. Notable sex-specific differences existed across histone modifications in these osteoblast subpopulations. Understanding the relationship between histone modifications and bone health will improve the assessment of ecological risk and public health impact of BaP pollution and further support the hypothesis that BaP-induced histone modifications are inherited over generations and involved in bone formation in an osteoblast subpopulation-specific manner.

Epigenetic clocks are valuable tools for assessing biological age. Exposure to secondhand smoke (SHS) and polycyclic aromatic hydrocarbons (PAHs) has been linked with epigenetic age deviation (EAD) in adults. However, associations in children remain largely unexplored. We investigated relationships between exposure-spanning prenatal, early postnatal, current (36-60 months, time of sample collection) periods-and EAD in preschool-aged children. DNA methylation was measured in buccal cells from 43 children (mean age: 4.1 years) in the CAries Risk from exposure to Environmental tobacco Smoke-Household Air Pollution Intervention Network cohort. SHS exposure was assessed using urinary cotinine and 3-hydroxycotinine (3-HC), while PAHs exposure was assessed via urinary 2-naphthol (2-NAP) and 1-hydroxypyrene (1-PYR). Nicotine equivalents were calculated as molar sum of cotinine + 3-HC. EAD was estimated using Horvath, Skin&Blood, Pediatric Buccal Epigenetic (PedBE), and DNA methylation-based telomere length (DNAmTL) clocks. Associations between exposures and EAD were evaluated using linear regression, adjusting for study site, mother's education, child's body mass index z-score, age, and sex. Chronological age significantly correlated with all epigenetic clocks (r = 0.37-0.78) and with DNAmTL estimator (r = -0.38). Current SHS exposure, as measured by urinary cotinine, was associated with Horvath EAD (B = 0.23 years, P = .05). Similarly, current 3-HC and nicotine equivalents were positively associated with PedBE EAD (B = 0.08 years, P = .04; B = 0.11 years, P = .05, respectively). Among PAH metabolites, current 2-NAP levels were associated with principal component-based Skin&Blood EAD (B = 0.21 years, P = .02) and PedBE EAD (B = 0.13 years, P = .05). Findings suggest early-life SHS and PAHs exposure may contribute to accelerated epigenetic aging in children.

Background: Repetitive DNA elements such as LINE1 have been proposed to support a redundant distributed, adaptive layer of gene regulation, contributing to "Epigenetic Intelligence" (EI). However, empirical evidence for their role in modulating inflammatory responses to environmental exposures remains limited.

Objectives: We investigated whether the association of PM with an aerodynamic diameter ≤10 µm (PM₁₀) with fibrinogen levels is modulated by LINE1 methylation (effect modification), acting as an epigenetic buffer of systemic inflammation in response to air pollution, looking at the EI hypothesis.

Methods: We analyzed data from the SPHERE cohort (n = 1630), a population-based study in Northern Italy. Daily residential exposure to PM₁₀ was estimated, and LINE1 methylation was assessed via pyrosequencing. Fibrinogen was used as a biomarker of systemic inflammation. Generalized Additive Models with tensor product interactions were used to evaluate the PM₁₀ × LINE1 interaction, adjusting for relevant confounders.

Results: The interaction between PM₁₀ exposure and LINE1 methylation was statistically supported (EDF ≈ 4.45, P < 0.001), with the model explaining ∼33% of deviance (adj. R² = 0.39). Individuals in the lowest tertile of LINE1 methylation exhibited a stronger positive association between PM₁₀ and fibrinogen, whereas those in the highest tertile showed a blunted response, suggesting a buffering modification effect. Results were confirmed by MARS models.

Conclusions: Our findings were coherent with the concept of EI. LINE1 methylation modulates the inflammatory response to environmental stressors, possibly acting as an adaptive epigenetic filter that buffers weak or transient signals. This distributed regulatory capacity may be critical for immune homeostasis under the dynamic environmental challenge.

Genomic imprinting is a phenomenon in which one parental allele is silenced epigenetically. My research has focused on the role of epigenetics in human health and disease since 1995 when we identified the first tumor suppressor gene that is also imprinted, the IGF2R. Subsequently, by using the agouti viable yellow (A^vy) mouse model, we demonstrated that increased maternal dietary exposure to methyl donors in utero altered offspring phenotype in adulthood by modifying the epigenome, providing a plausible mechanism for the developmental origins of health and disease (DOHaD). Consequently, the field of epigenetics can be thought of as the "science of hope," since personal changes in diet and physical activity can potentially alter the epigenome to prevent chronic disease formation, and potentially, even ameliorate the negative effects of environmental exposures to chemical and physical toxicants. In this perspectives article, I address a series of questions posed about the field of environmental epigenetics, and discuss the role that the environmentally labile cis-acting, imprint regulatory elements in the human genome (i.e. the human imprintome) and the correlated regions of systemic interindividual variation (CoRSIVs) play in disease formation and behavioral development.

Traditional breeding programs have largely focused on genetics, often overlooking environmental and epigenetic influences on phenotypic variability. Current methods for developing epigenetic biomarkers (EBs) with machine learning (ML) algorithms require extensive data, making them costly and time-intensive. In this study, using a fish as a model, we analysed ~500 000 CpG loci in samples from 60 different families to develop EBs for broodstock selection. To address limited sample sizes at the sequencing stage, we combined careful sample selection, statistical filtering, and various feature selection and ML algorithms. As a result, we identified three heritable CpGs sites in sire sperm associated with three key performance indicators in their offspring: biomass, fast-growing females, and resistance to the masculinizing effects of high temperature. Then, we were able to build a model successfully predicting the best sire broodstock based on DNA methylation levels of these EBs. This model was validated across three independent trials, including one involving an external cohort of fish with differentiated genetic background, thereby confirming its robustness beyond the training population. Yield was increased up to 1.4-fold when including epigenetic selection into the genetic selection program as compared with genetic selection alone. In summary, we present a cost-effective strategy for integrating epigenetic and genetic selection in the context of animal production. Furthermore, this method also can be applied to assess the impact of environmental factors into the broodstock and on samples where obtaining information can be challenging, such as in the study of the epigenetic basis of rare diseases, and the application of epigenetic markers in conservation biology.

High-altitude adaptation in Andean populations has traditionally been studied through the lens of genetic variation, with limited exploration of epigenetic mechanisms such as DNA methylation. Here, we present the first whole-methylome data comparing Indigenous populations residing in high-altitude regions of the Ecuadorian Andes to those in low-altitude Peruvian Amazon regions bordering the Andes. By leveraging whole-methylome sequencing rather than methylation arrays, we achieved an unprecedented resolution of epigenetic variation, revealing novel insights into altitude-associated adaptations. We identified significant differentially methylated regions in genes involved in hypoxia response and skin pigmentation that differ from patterns previously observed in high-altitude Tibetan individuals [Lin et al. (Genome-wide DNA methylation landscape of four Chinese populations and epigenetic variation linked to Tibetan high-altitude adaptation. Science China Life Sciences 2023;66:2354-69. https://doi.org/10.1007/s11427-022-2284-8.)]. Our findings highlight the influence that altitude-specific environmental pressures, such as hypoxia and ultraviolet radiation, can have on the epigenetic landscapes observed between human populations. Importantly, we uncovered unique regulatory methylation signatures in the hypoxia response pathways of Andean populations, underscoring a distinct epigenetic trajectory compared to other high-altitude groups. This study represents a step forward in understanding Indigenous American genomic plasticity and demonstrates the value of whole-methylome data over methylation arrays in capturing the complex interplay between epigenetics and the environment. These results support a new approach to studying altitude plasticity and underscore the critical role of epigenetics in shaping population-specific cellular responses in Indigenous communities.

Female survivors of physical or psychological violence, including sexual violence, report significant long-term consequences defined as post-traumatic stress disorder (PTSD). Among these, depression, affective difficulties, anomalous behaviours, and worsened reproductive health may also affect offspring through transgenerational transmission involving primordial germ cells (PGCs) and/or through social transmission and acquisition of behavioural patterns from parent(s) to children. The concept of epigenomic modification involves several molecular targets that are sensitive to environmental stressors, which tune gene activity and expression. DNA methylation, histone acetylation, ncRNAs, telomere attrition, and mitochondrial dysfunction cooperate in maintaining homeostasis and may affect genes involved in key pathways, such as the hypothalamic-pituitary-adrenal axis, mediating the integrated homeostatic response to stressors. The most investigated genes were those implicated in neuroendocrine stress responses; dopamine, norepinephrine, and serotonin signalling; apoptosis; insulin secretion; neuroplasticity; reproduction; foetal growth; and cancer (e.g. MAOA, BRSK2, ADCYAP1, BDNF, DRD2, IGF2, H19). Additional investigated genes were those involved in other important functions, such as neuropeptide binding, immunoregulation, histone deacetylase/demethylase, inflammatory response, and serotonin uptake, yielding interesting but preliminary or not completely replicated findings (e.g. CRHR1, FKBP5, KDM1A, NR3C1, PRTFDC1, and SLC6A4). The assumption that epigenetic traits induced by negative experiences can be reversed by appropriate social, psychological, and pharmacological interventions has prompted the scientific community to investigate the relationship between epigenetic mechanisms and physical and psychological violence. This can help to identify direct links or epigenetic marks useful for optimizing personalized interventions encompassing the genetic, neuropsychiatric, social, and forensic medicolegal fields. Future research should be conducted with extreme caution to evaluate the long-term effects of such strategies and assess whether the immediate observed effects are maintained.

Organisms detect harmful environmental conditions and employ strategies to protect themselves. Additionally, they can communicate these experiences to the next generation or beyond through non-DNA sequence-based mechanisms, known as intergenerational or transgenerational epigenetic inheritance, respectively. Using a specialist larval parasitoid, Leptopilina boulardi, and its host, Drosophila melanogaster, we demonstrate that parental experience of parasitic stress leads to increased survivability in the immediate offspring of the host. Furthermore, we observe that this increased survivability in response to parasitic stress is transmitted transgenerationally when the grandparents, but not the parents, have been exposed to the parasitoid. This increased survivability is primarily inherited through male parents, with one form of effect being enhanced immune priming at the larval stage. Our study suggests that stress exposure during the pre-adult stage of the host provides lifetime benefits for its progeny, enabling them to better cope with future parasitic attacks.

The increasing incidence of opioid use during pregnancy has led to a rise in the number of infants exposed to opioids in utero. Prenatal opioid exposure may have consequences for health and (neuro)development, including neonatal opioid withdrawal syndrome (NOWS). It is unknown which infants are at greatest risk for NOWS. DNA methylation (DNAm) is an epigenetic mark reflecting both allelic variation and environmental exposures, which may provide biomarkers for prenatal opioid exposure and infant NOWS. The placenta is an accessible, biologically relevant tissue in which to directly investigate the epigenetic effects of prenatal opioid exposure. Therefore, the aims of this study were to examine whether prenatal opioid exposure is associated with differential DNAm, including epigenetic age acceleration (EAA) in the placenta. We performed an epigenome-wide association study based on co-methylated regions and single CpG sites in placental samples from in utero opioid-exposed (n = 19) and nonexposed infants (n = 143), correcting for potential confounders. We did not identify statistically significant differential DNAm profiles, but the strongest associations were found for cg06621211; cg18688392 (ZMIZ1, adjusted P = .068) and cg04460738 (KCNMA1, adjusted P = .068), although effect sizes were very small. One of these DNAm patterns (cg06621211) was in part under control of genetic variants through methylation quantitative trait loci. The involved single nucleotide polymorphism did not show significant associations in recent genome-wide association studies for phenotypes related to substance use, and the finding was not driven by potential co-occurring substance use based on sensitivity analyses. There was also no association between placental EAA and in utero opioid exposure. In conclusion, placental DNAm showed limited associations with in utero opioid exposure and NOWS diagnosis.

Evidence has linked maternal exposure to stress during pregnancy with poor offspring health and neurodevelopmental outcomes. However, the precise mechanism by which this may occur has not been fully elucidated. In this study, we examined whether maternal perceived stress during pregnancy was associated with newborn blood DNA methylation (DNAm) in hypothalamic-pituitary-adrenal axis-related genes (NR3C1, FKBP5, and HSD11B2) in single CpG site and gene-based analyses. We analysed a subset of 661 mother-child pairs from the Environmental Influences on Child Health Outcomes cohort study that met our analytic inclusion criteria. Maternal perceived stress was measured during pregnancy using the perceived stress scale, and newborn DNAm was measured using the Illumina 450K and EPIC Beadchips in cord blood and dried blood spots. Single-site associations were evaluated using linear regression models, and gene-based associations were evaluated using mean burden and variance component tests, adjusted for sociodemographic and lifestyle covariates. Sex-stratified models were used to evaluate sex differential effects. Prenatal perceived stress was statistically significantly associated with newborn DNAm in one CpG site (cg06613263) in NR3C1 and with aggregate DNAm in NR3C1 and FKBP5. Aggregate DNAm in FKBP5 was more strongly associated with prenatal perceived stress in female infants. These results may have important implications for improving offspring health and well-being by providing molecular targets that can be used to identify high-risk individuals and as a basis for developing and evaluating effective behaviour and pharmaceutical interventions.