Environmental Epigenetics最新文献

{"title":"Triphenyl phosphate induces coordinated DNA methylation and gene expression changes in aquatic embryonic cells.","authors":"Logan S Germain, Benjamin P Ott, Charles C T Hindmarch, Louise M Winn","doi":"10.1093/eep/dvag003","DOIUrl":"https://doi.org/10.1093/eep/dvag003","url":null,"abstract":"<p><p>Triphenyl phosphate (TPHP) is a high-production-volume flame retardant and plasticizer that is widely detected in the environment and in biomonitoring studies. TPHP exposure has been linked to endocrine disruption, metabolic disruption, genotoxicity, and neurodevelopmental effects <i>in vitro</i> and <i>in vivo</i>. The diverse toxicological outcomes across studies suggest disruption of fundamental regulatory processes, such as epigenetic control of gene expression. Here, we used an immortalized embryonic cell line derived from steelhead trout (STE-137) to investigate coordinated transcriptional and epigenetic responses to TPHP exposure. Cells were exposed to 0 or 80 μM TPHP for 24 h, followed by RNA sequencing (RNA-seq) or whole-genome bisulfite sequencing (WGBS). Differential expression analysis identified 1622 significant genes, with significant enrichment of DNA replication and repair, cell cycle regulation, and endocrine signaling pathways and prominent lipid metabolism genes. Weighted gene co-expression network analysis revealed modules highly correlated with exposure, including those enriched for protein and amino acid metabolism, ion transport, and genomic stability. WGBS methylome analysis detected 382 differentially methylated regions (DMRs), the majority hypermethylated and within gene bodies. Notable alterations included a DMR in the htr2cl1 gene, encoding a serotonin receptor, and the brca2 gene, a key DNA damage enzyme. Integration of RNA-seq and WGBS datasets identified nine genes with both expression and methylation changes, alongside altered gene expression of several key epigenetic regulators. Our results provide molecular evidence for early initiating events relevant to adverse outcome pathways and highlight the importance of epigenetic endpoints in developmental toxicity assessment.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag003"},"PeriodicalIF":3.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12907732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146212678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental Epigenetics 2026 Update.","authors":"Michael K Skinner","doi":"10.1093/eep/dvag002","DOIUrl":"https://doi.org/10.1093/eep/dvag002","url":null,"abstract":"","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag002"},"PeriodicalIF":3.2,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12907727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146212671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preeclampsia and environmental epigenomics: the emerging role of air pollution, gut microbiome, and maternal exposures in disease programming.","authors":"Geethika Yelleti, Nihaal Maripini, Varashree Bolar Suryakanth","doi":"10.1093/eep/dvag001","DOIUrl":"https://doi.org/10.1093/eep/dvag001","url":null,"abstract":"<p><p>Preeclampsia (PE) remains a major contributor of maternal and fetal morbidity and mortality worldwide, affecting 2%-8% of pregnancies. While genetic predisposition, placental dysfunction, and angiogenic imbalance remain central to PE pathophysiology, emerging observational evidence suggests potential associations between environmental factors, epigenetic modifications, and PE development. This review consolidates available research linking environmental exposures, particularly air pollution, maternal gut microbiome composition, and dietary habits, with changes in epigenetic markers during pregnancy that may influence PE susceptibility. We synthesize findings from epidemiological studies, mechanistic research, and biomarker studies across this research area. However, definitive causal evidence linking specific environmental exposures to PE through epigenetic mechanisms remains limited. The majority of existing studies employ observational designs or focus on biological mechanisms; well-designed prospective cohorts incorporating direct environmental measurements and randomized intervention trials are lacking. Circulating biomarkers, including microRNAs and DNA methylation patterns, show associations with both PE status and prior environmental exposure, providing biological support for the concept that environmental factors may influence PE development. The maternal gut microbiome demonstrates dysbiosis in PE patients, and mechanistic studies in animal models suggest that microbiota-derived metabolites may influence placental development through epigenetic pathways; however, clinical evidence in humans remains preliminary. Integration of environmental exposure assessment with multi-omics profiling in large prospective studies is necessary to establish whether environmental factors causally contribute to PE pathogenesis. Future research combining detailed environmental characterization, longitudinal epigenomic profiling, and rigorous causal inference methods will be essential to translate these mechanistic insights into prevention and therapeutic strategies.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag001"},"PeriodicalIF":3.2,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12907729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146212662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An exploratory analysis of miRNAs measured in placental tissue and their associations with prenatal exposure to household air pollution.","authors":"Abigail Gaylord, Mohammed Nuhu Mujtaba, Michelle Li, Musah Osei, Oscar Agyei, Steven N Chillrud, Seyram Kaali, Darby W Jack, Kwaku Poku Asante, Haotian Wu, Alison G Lee","doi":"10.1093/eep/dvaf036","DOIUrl":"10.1093/eep/dvaf036","url":null,"abstract":"<p><p>Household air pollution (HAP) has been associated with adverse pregnancy and birth outcomes, but the underlying mechanisms remain unclear. Pollutants can cross the placenta, potentially causing dysregulation of the crucial organ. Placental microRNAs (miRNAs) may serve as biomarkers of placental health, but studies of prenatal air pollutant exposure and placental miRNAs using non-targeted approaches have been scarce. We leveraged personal air monitoring data from mothers enrolled in the Ghana Randomized Air Pollution and Health Study to estimate prenatal exposure levels to carbon monoxide (CO) and particulate matter <2.5 µm (PM_2.5). Placental tissue small RNA was sequenced and aligned to miRbase v22. We used sparse principal components analyses (sPCAs) to identify candidate placental miRNAs associated with prenatal CO (<i>N</i> = 133) and PM_2.5 (<i>N</i> = 85) exposure. Associations between candidate miRNAs and prenatal exposures were assessed using linear regressions. We identified four placental miRNAs upregulated with prenatal CO exposure (miR-128-3p, miR-423-3p, miR-671-3p, and miR-744-5p) and five downregulated miRNAs (miR-29b-3p, miR-30e-5p, miR-101-3p, miR-130a-3p, and miR-376b-3p) at <i>P</i> < 0.1. Among female infants only, five miRNAs were downregulated (miR-101-3p, miR-130a-3p, miR-19b-3p, miR-106b-5p, and miR-301a-3p) and one upregulated (miR-22-3) with CO exposure (<i>P</i> < 0.1). We did not identify any associations between placental miRNAs and prenatal PM_2.5 exposure. Our results support associations of prenatal CO exposure with differential expressions of critical placental miRNAs that have been implicated in placental disorders by previous studies. This is the first study to examine associations of these exposures with placental miRNAs using a non-candidate approach and lays the groundwork for targeted studies of placental miRNAs associated with prenatal HAP exposure.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvaf036"},"PeriodicalIF":3.2,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12914214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146225962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of a prenatal exposure mixture of metals on DNA methylation-derived cell-type composition in cord blood.","authors":"Sandra India-Aldana, Hachem Saddiki, Luigi Annicchiarico, Alexandra Chirvasuta, Corina Lesseur, Julio Landero, Damaskini Valvi, Alejandra Cantoral, Andrea A Baccarelli, Martha María Téllez-Rojo, Robert O Wright, Elena Colicino","doi":"10.1093/eep/dvaf035","DOIUrl":"10.1093/eep/dvaf035","url":null,"abstract":"<p><p>Metal(loid) exposure can exert immunotoxic effects, including changes in white blood cell proportions. The impact from metal exposure mixtures during pregnancy has not been examined in relation to cell-type composition at birth. Our aim was to evaluate the associations between a prenatal metal(loid) exposure mixture and cord blood DNA methylation-derived cell-type composition. We leveraged the PROGRESS birth cohort with measured prenatal immunotoxic metal(loid)s in blood (manganese, lead) and urine (arsenic, cadmium) and DNA methylation-derived cell-type composition from cord blood (<i>n</i> = 428). We used the novel Dirichlet Bayesian Weighted Quantile Sum regression to elucidate the association of metal mixtures on a compositional outcome with several DNA methylation-derived cell types: granulocytes (GR), CD4⁺ and CD8⁺ T-cells, B-cells, monocytes, natural killer (NK) cells, and nucleated red blood cells (nRBCs). We also conducted stratified analyses by fetal sex. We observed no associations in the overall population. In sex-stratified models, a one-quartile increase in metal mixture among the pregnant women carrying a female was associated with a 4.85% [95% credible intervals (CrI): 1.11%, 8.81%] increase in GR proportion, driven by arsenic. Conversely, a one-quartile increase in metal mixture in women carrying a male was marginally associated with a 3.44% (95% CrI: -7.08%, 0.37%; 80%CrI: -5.83%, -1.01%) decrease in GR proportion, driven by cadmium. We also observed marginal metal mixture associations with higher proportions of CD8⁺ T-cells in women carrying a male and lower proportion of NK cells and nRBCs in women carrying a female. Our findings suggest a potential differential metal mixture-cell composition associations given by fetal sex.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvaf035"},"PeriodicalIF":3.2,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12914215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146225996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generational stability of environmentally induced epigenetic transgenerational inheritance of adult-onset disease over ten mammalian generations.","authors":"Alexandra A Korolenko, Eric E Nilsson, Sarah De Santos, Michael K Skinner","doi":"10.1093/eep/dvaf033","DOIUrl":"10.1093/eep/dvaf033","url":null,"abstract":"<p><p>In traditional models of <i>Drosophila</i> flies and <i>Caenorhabditis elegans</i> worms, epigenetic transgenerational inheritance has persisted for hundreds of generations. Mammalian studies, however, have primarily investigated up to three or four generations. Environmental exposures to toxicants or other stressors have been linked to epigenetic transgenerational inheritance. Changes within the epigenome have the potential to alter gene expression and genetic processes, as well as potentially alter phenotypes and evolution in all organisms. In this study, an outcrossed mammalian colony of outbred rats was bred for 10 successive generations and assessed for epigenetic alterations and incidence of pathological abnormalities. The hypothesis tested was that epigenetic transgenerational inheritance of disease would be maintained for 10 generations. Sperm from male rats were analysed for DNA methylation and pathology abnormalities in the outcross female and male lineage rats in successive generations. Effects on male sperm were observed in differential DNA methylated regions in both lineages. A dramatic increase in apoptosis of male spermatogenic cells in the testes for both male and female lineages was observed. Pathology of different tissue types was assessed by artificial intelligence-based technologies using deep learning histology protocols developed. Observations showed a dramatic increase in disease incidence within the 10th generation (F13) compared to the control lineage for kidney, ovary, prostate, and testis for both outcross lineages. As previously observed, no gross pathologies were observed in other organs. Observations demonstrate the long-term impact of ancestral exposures on epigenetic modifications and health outcomes across multiple generations are stable for 10 generations in mammals.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"11 1","pages":"dvaf033"},"PeriodicalIF":3.2,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12720976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parental benzo[a]pyrene exposure impacts histone modifications in osteoblast subpopulations.","authors":"Alexis S Trujillo, Remi O Labeille, Rijith Jayarajan, Dylan Mack, Frauke Seemann","doi":"10.1093/eep/dvaf032","DOIUrl":"10.1093/eep/dvaf032","url":null,"abstract":"<p><p>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 <i>twist:dsred/col10a1:gfp</i> medaka (<i>Oryzias latipes</i>) 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 <i>twist</i> ⁺ cells, BaP exposure significantly reduced H3K9me3 marks in both male and female fish. Significant reductions of H3K9me3 and H4K5ac/K8ac/K12ac were observed in <i>col10a1</i> ⁺ 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.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"11 1","pages":"dvaf032"},"PeriodicalIF":3.2,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12699992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-dependent biobehavioural responses to transgenerational maternal stress: evidence of stress resilience and vulnerability in the F3 generation.","authors":"Jamshid Faraji, Nicola Schatz, Stephanie King, Nasrin Soltanpour, Gerlinde A S Metz","doi":"10.1093/eep/dvaf031","DOIUrl":"10.1093/eep/dvaf031","url":null,"abstract":"<p><p>Maternal prenatal stress can determine stress resilience and vulnerability of future generations. However, the extent to which the biological sex of the descendants determines the response to ancestral stress is not fully understood. In this study, neurohormonal responses and exploratory and anxiety-like behaviours were examined in third-generation (F3) male and female rats born to non-stressed and transgenerationally stressed lineages, where maternal stress was induced only in pregnant females of the ancestral F0 generation. While ancestral stress in F3 females did not alter hypothalamic-pituitary-adrenal (HPA) axis activity, F3 males born to F0 stressed mothers exhibited HPA axis hyperactivity compared to non-stressed males. By contrast, females revealed significantly higher corticosterone levels than males. Moreover, ancestral stress elevated concentrations of the cytokines interleukin-1β (IL-1β) and IL-10 exclusively in females. Ancestral maternal stress also produced task-specific differences in depressive- and anxiety-like symptoms in the F3 generation, particularly in females. Specifically, F3 female behaviour within the open field and elevated plus maze tasks was more affected by ancestral maternal stress than that of F3 males. Supported by correlational analysis, the findings demonstrate that F3 female offspring are more sensitive than males to the neuroimmunological and behavioural impacts of maternal prenatal stress, despite the absence of elevated HPA axis activity. In contrast, males primarily responded with HPA axis activity upregulation, which compounded effects on their behavioural profile. The present study supports the notion that maternal stress, across generations, is likely to epigenetically programme sex-specific behavioural, physiological, and immunological phenotypes in remote offspring, with particular vulnerability in females.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"11 1","pages":"dvaf031"},"PeriodicalIF":3.2,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12728981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early-life exposure to secondhand smoke and polycyclic aromatic hydrocarbons: associations with epigenetic aging among children.","authors":"Sneha S Patil, Anne K Bozack, Ajay Pillarisetti, Smita S Patil, Kyle Steenland, Kalpana Balakrishnan, Lance A Waller, Shirin Jabbarzadeh, Jennifer Peel, Thomas F Clasen, Dana Boyd Barr, Naveen Puttaswamy, Andres Cardenas","doi":"10.1093/eep/dvaf030","DOIUrl":"10.1093/eep/dvaf030","url":null,"abstract":"<p><p>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 <i>z</i>-score, age, and sex. Chronological age significantly correlated with all epigenetic clocks (<i>r</i> = 0.37-0.78) and with DNAmTL estimator (<i>r</i> = -0.38). Current SHS exposure, as measured by urinary cotinine, was associated with Horvath EAD (<i>B</i> = 0.23 years, <i>P</i> = .05). Similarly, current 3-HC and nicotine equivalents were positively associated with PedBE EAD (<i>B</i> = 0.08 years, <i>P</i> = .04; <i>B</i> = 0.11 years, <i>P</i> = .05, respectively). Among PAH metabolites, current 2-NAP levels were associated with principal component-based Skin&Blood EAD (<i>B</i> = 0.21 years, <i>P</i> = .02) and PedBE EAD (<i>B</i> = 0.13 years, <i>P</i> = .05). Findings suggest early-life SHS and PAHs exposure may contribute to accelerated epigenetic aging in children.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"11 1","pages":"dvaf030"},"PeriodicalIF":3.2,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12631029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145586381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redundancy, noise, and plasticity: repetitive DNA as an epigenetic intelligence backbone of inflammatory regulation.","authors":"Valentina Bollati, Elia Biganzoli","doi":"10.1093/eep/dvaf028","DOIUrl":"10.1093/eep/dvaf028","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>We analyzed data from the SPHERE cohort (<i>n</i> = 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.</p><p><strong>Results: </strong>The interaction between PM₁₀ exposure and LINE1 methylation was statistically supported (EDF ≈ 4.45, <i>P</i> < 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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"11 1","pages":"dvaf028"},"PeriodicalIF":3.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12587764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}