Environmental Epigenetics最新文献

{"title":"Effects of cannabis on congenital limb anomalies in 14 European nations: A geospatiotemporal and causal inferential study.","authors":"Albert Stuart Reece,&nbsp;Gary Kenneth Hulse","doi":"10.1093/eep/dvac016","DOIUrl":"https://doi.org/10.1093/eep/dvac016","url":null,"abstract":"<p><p>Cannabinoid exposure is increasing in some European nations. Europe therefore provides an interesting test environment for the recently reported link between cannabis exposure and congenital limb anomaly (CLA) rates (CLARs). Exponential genotoxic dose-response relationships make this investigation both intriguing and imperative. Annual CLAR in 14 nations were from Epidemiological Surveillance of Congenital Anomalies. Drug use rates were from European Monitoring Centre for Drugs and Drug Dependency. Median household income was from the World Bank. <i>E</i>-values provide a quantitative measure of robustness of results to confounding by extraneous covariates. Inverse probability weighting is an important technique for equalizing exposures across countries and removing sources of bias. Rates of CLA, hip dysplasia and the whole group of limb anomalies were higher in countries with increasing daily cannabis use (<i>P</i> = 1.81 × 10^-16, 0.0005 and 2.53 × 10^-6, respectively). In additive inverse-probability-weighted panel models, the limb reduction-resin Δ9-tetrahydrocannabinol (THC) concentration <i>E</i>-value estimate was 519.93 [95% lower bound (mEV) 49.56], order Resin > Herb ≫ Tobacco > Alcohol. Elevations were noted in 86% <i>E</i>-value estimates and 70.2% of mEVs from 57 <i>E</i>-value pairs from inverse-probability-weighted panel models and from spatial models. As judged by the mEV the degree of association with metrics of cannabis exposure was hip dysplasia > polydactyly > syndactyly > limb anomalies > limb reductions with median <i>E</i>-value estimates from 3.40 × 10⁶⁵ to 7.06 and median mEVs from 6.14 × 10³³ to 3.41. Daily cannabis use interpolated was a more powerful metric of cannabis exposure than herb or resin THC exposure. Data indicate that metrics of cannabis exposure are closely linked with CLAR and satisfy epidemiological criteria for causality. Along with Hawaii and the USA, Europe now forms the third international population in which this causal link has been demonstrated. Cannabis as a predictor of limb anomalies was more potent than tobacco or alcohol. Cannabinoid access should be restricted to protect public health and the community genome/epigenome transgenerationally.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/25/82/dvac016.PMC9364687.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40697923","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":"The impact of prenatal and early-life arsenic exposure on epigenetic age acceleration among adults in Northern Chile.","authors":"Anne K Bozack,&nbsp;Philippe Boileau,&nbsp;Alan E Hubbard,&nbsp;Fenna C M Sillé,&nbsp;Catterina Ferreccio,&nbsp;Craig M Steinmaus,&nbsp;Martyn T Smith,&nbsp;Andres Cardenas","doi":"10.1093/eep/dvac014","DOIUrl":"https://doi.org/10.1093/eep/dvac014","url":null,"abstract":"<p><p>Exposure to arsenic affects millions of people globally. Changes in the epigenome may be involved in pathways linking arsenic to health or serve as biomarkers of exposure. This study investigated associations between prenatal and early-life arsenic exposure and epigenetic age acceleration (EAA) in adults, a biomarker of morbidity and mortality. DNA methylation was measured in peripheral blood mononuclear cells (PBMCs) and buccal cells from 40 adults (median age = 49 years) in Chile with and without high prenatal and early-life arsenic exposure. EAA was calculated using the Horvath, Hannum, PhenoAge, skin and blood, GrimAge, and DNA methylation telomere length clocks. We evaluated associations between arsenic exposure and EAA using robust linear models. Participants classified as with and without arsenic exposure had a median drinking water arsenic concentration at birth of 555 and 2 μg/l, respectively. In PBMCs, adjusting for sex and smoking, exposure was associated with a 6-year PhenoAge acceleration [<i>B</i> (95% CI)<i> </i>= 6.01 (2.60, 9.42)]. After adjusting for cell-type composition, we found positive associations with Hannum EAA [<i>B</i> (95% CI) = 3.11 (0.13, 6.10)], skin and blood EAA [<i>B</i> (95% CI) = 1.77 (0.51, 3.03)], and extrinsic EAA [<i>B</i> (95% CI) = 4.90 (1.22, 8.57)]. The association with PhenoAge acceleration in buccal cells was positive but not statistically significant [<i>B</i> (95% CI) = 4.88 (-1.60, 11.36)]. Arsenic exposure limited to early-life stages may be associated with biological aging in adulthood. Future research may provide information on how EAA programmed in early life is related to health.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6a/e2/dvac014.PMC9235373.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40409657","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":"Assessment of parental benzo[a]pyrene exposure-induced cross-generational neurotoxicity and changes in offspring sperm DNA methylome in medaka fish.","authors":"Teng Wan,&nbsp;Doris Wai-Ting Au,&nbsp;Jiezhang Mo,&nbsp;Lianguo Chen,&nbsp;Kwok-Ming Cheung,&nbsp;Richard Yuen-Chong Kong,&nbsp;Frauke Seemann","doi":"10.1093/eep/dvac013","DOIUrl":"https://doi.org/10.1093/eep/dvac013","url":null,"abstract":"<p><p>Previous studies have revealed that DNA methylation changes could serve as potential genomic markers for environmental benzo[a]pyrene (BaP) exposure and intergenerational inheritance of various physiological impairments (e.g. obesity and reproductive pathologies). As a typical aromatic hydrocarbon pollutant, direct BaP exposure has been shown to induce neurotoxicity. To unravel the inheritance mechanisms of the BaP-induced bone phenotype in freshwater medaka, we conducted whole-genome bisulfite sequencing of F1 sperm and identified 776 differentially methylated genes (DMGs). Ingenuity pathway analysis revealed that DMGs were significantly enriched in pathways associated with neuronal development and function. Therefore, it was hypothesized that parental BaP exposure (1 μg/l, 21 days) causes offspring neurotoxicity. Furthermore, the possibility for sperm methylation as an indicator for a neurotoxic phenotype was investigated. The F0 adult brains and F1 larvae were analyzed for BaP-induced direct and inherited toxicity. Acetylcholinesterase activity was significantly reduced in the larvae, together with decreased swimming velocity. Molecular analysis revealed that the marker genes associated with neuron development and growth (<i>alpha1-tubulin, mbp, syn2a, shh</i>, and <i>gap43</i>) as well as brain development (<i>dlx2, otx2</i>, and <i>krox-20</i>) were universally downregulated in the F1 larvae (3 days post-hatching). While parental BaP exposure at an environmentally relevant concentration could induce neurotoxicity in the developing larvae, the brain function of the exposed F0 adults was unaffected. This indicates that developmental neurotoxicity in larvae may result from impaired neuronal development and differentiation, causing delayed brain growth. The present study demonstrates that the possible adverse health effects of BaP in the environment are more extensive than currently understood. Thus, the possibility of multigenerational BaP toxicity should be included in environmental risk assessments.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9c/db/dvac013.PMC9233418.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40409658","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":"Congenital anomaly epidemiological correlates of Δ8THC across USA 2003-16: panel regression and causal inferential study.","authors":"Albert Stuart Reece,&nbsp;Gary Kenneth Hulse","doi":"10.1093/eep/dvac012","DOIUrl":"https://doi.org/10.1093/eep/dvac012","url":null,"abstract":"<p><p>Δ8-Tetrahydrocannabinol (Δ8THC) is marketed in many US states as 'legal weed'. Concerns exist relating to class-wide genotoxic cannabinoid effects. We conducted an epidemiological investigation of Δ8THC-related genotoxicity expressed as 57 congenital anomaly (CA) rates (CARs) in the USA. CARs were taken from the Centers for Disease Control, Atlanta, Georgia. Drug exposure data were taken from the National Survey of Drug Use and Health, with a response rate of 74.1%. Ethnicity and income data were taken from the US Census Bureau. National cannabinoid exposure was taken from Drug Enforcement Agency publications and multiplied by state cannabis use data to derive state-based estimates of Δ8THC exposure. At bivariate continuous analysis, Δ8THC was associated with 23 CAs on raw CA rates, 33 CARs after correction for early termination for anomaly estimates and 41 on a categorical analysis comparing the highest and lowest exposure quintiles. At inverse probability weighted multivariable additive and interactive models lagged to 0, 2 and 4 years, Δ8THC was linked with 39, 8, 4 and 9 CAs. Chromosomal, cardiovascular, gastrointestinal, genitourinary, limb, central nervous system (CNS) and face systems were particularly affected. The minimum <i>E</i>-values ranged to infinity. Both the number of anomalies implicated and the effect sizes demonstrated were much greater for Δ8THC than for tobacco and alcohol combined. Δ8THC appears epidemiologically to be more strongly associated with many CAs than for tobacco and alcohol and is consistent with a cannabinoid class genotoxic/epigenotoxic effect. Quantitative causality criteria were fulfilled, and causal relationships either for Δ8THC or for cannabinoid/s, for which it is a surrogate marker, may be in operation.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5e/00/dvac012.PMC9245652.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40466413","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":"Nephrotoxicity of perfluorooctane sulfonate (PFOS)-effect on transcription and epigenetic factors.","authors":"Yi Wen, Faizan Rashid, Zeeshan Fazal, Ratnakar Singh, Michael J Spinella, Joseph Irudayaraj","doi":"10.1093/eep/dvac010","DOIUrl":"10.1093/eep/dvac010","url":null,"abstract":"<p><p>Perfluorooctane sulfonate (PFOS) is a widespread persistent environmental pollutant implicated in nephrotoxicity with altered metabolism, carcinogenesis, and fibrosis potential. We studied the underlying epigenetic mechanism involving transcription factors of PFOS-induced kidney injury. A 14-day orally dosed mouse model was chosen to study acute influences <i>in vivo</i>. Messenger RNA expression analysis and gene set enrichment analysis were performed to elucidate the relationship between epigenetic regulators, transcription factors, kidney disease, and metabolism homeostasis. PFOS was found to accumulate in mouse kidney in a dose-dependent manner. Kidney injury markers <i>Acta2</i> and <i>Bcl2l1</i> increased in expression significantly. Transcription factors, including <i>Nef2l2, Hes1, Ppara</i>, and <i>Ppard,</i> were upregulated, while <i>Smarca2</i> and <i>Pparg</i> were downregulated. Furthermore, global DNA methylation levels decreased and the gene expression of histone demethylases <i>Kdm1a</i> and <i>Kdm4c</i> were upregulated. Our work implicates PFOS-induced gene expression alterations in epigenetics, transcription factors, and kidney biomarkers with potential implications for kidney fibrosis and kidney carcinogenesis. Future experiments can focus on epigenetic mechanisms to establish a panel of PFOS-induced biomarkers for nephrotoxicity evaluation.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2022-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45927022","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":"Deciphering the RNA universe in sperm in its role as a vertical information carrier.","authors":"Miriam Kretschmer, Katharina Gapp","doi":"10.1093/eep/dvac011","DOIUrl":"10.1093/eep/dvac011","url":null,"abstract":"<p><p>The inheritance of neurophysiologic and neuropsychologic complex diseases can only partly be explained by the Mendelian concept of genetic inheritance. Previous research showed that both psychological disorders like post-traumatic stress disorder and metabolic diseases are more prevalent in the progeny of affected parents. This could suggest an epigenetic mode of transmission. Human studies give first insight into the scope of intergenerational influence of stressors but are limited in exploring the underlying mechanisms. Animal models have elucidated the mechanistic underpinnings of epigenetic transmission. In this review, we summarize progress on the mechanisms of paternal intergenerational transmission by means of sperm RNA in mouse models. We discuss relevant details for the modelling of RNA-mediated transmission, point towards currently unanswered questions and propose experimental considerations for tackling these questions.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2022-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48717375","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":"Marion Julia Lamb (29 July 1939–12 December 2021)","authors":"E. Jablonka","doi":"10.1093/eep/dvac009","DOIUrl":"https://doi.org/10.1093/eep/dvac009","url":null,"abstract":"Marion Julia Lamb, a pioneer in the field of evolutionary epigenetics, died in London on the 12th of December 2021 at the age of 82 of lung cancer. Marion was an original and accomplished scientist and her intellectual brilliance was combined with deep political and intellectual courage, a fascination with the natural world and an almost fanatical studiousness. Coming from a natureand bookloving working-class family, she roamed, as a child, the coasts and estuaries of East Anglia, watching birds, investigating rock pools, turning every rotten log, developing the naturalist’s ardent and focused competence. She was always grateful to her parents for the freedom they gave her and for their one demand—that she ‘does her best’—whatever ‘best’ may be. And indeed she did—from decorating her flat to gardening, sailing, teaching and researching. Her intellect was clear and powerful and she excelled in everything she ever put it to—as a 16-year-old lab assistant in Max Perutz’s lab in Cambridge during her high-school vacations, as a brilliant university student (she shared with Robin Weiss the Francis Perch Bedford Prize for the best first degree in University College London), as an inspiring teacher and as a ground-breaking scientist. Marion loved the elegant beauty of genetics, and when John Maynard Smith, her genetics teacher in University College London (UCL) suggested that she does a PhD with him, she was delighted. Her thesis on ‘Radiation and Ageing in Drosophila’ was awarded a PhD in 1965. Her laboratory research was conducted in UCL, Harwell and Birkbeck College (where she became a senior lecturer) and was concerned mainly with various aspects of the biology and genetics of ageing, using Drosophila as a research tool. Her large body of experimental work on ageing, radiation biology and mutagenesis, 25 papers altogether, stood the test of time, and she wrote a highly acclaimed, crystal-clear and concise book ‘The Biology of Ageing’ (published by Blackie, 1), on which several advanced courses in the biology of ageing around the world were based. Evolutionary biology was Marion’s passion and guide since she was a high-school student and read Huxley’s Evolution: The Modern Synthesis. She told me that the first tutorial she ever attended as a first-year student in UCL was on Waddington’s The Strategy of the Genes and that it blew her mind. Our first conversation, in 1973, also happened to be about Waddington (I discovered Waddington, independently, through reading Arthur Koestler’s Ghost in the Machine, well before I knew any genetics). I was a first-year student, and she was my genetics teacher in Birkbeck College, where I spent a year. I asked her if she knowsWaddington and she looked at me with a wry smile and suggested that I learn to walk before I start running. I ended up doing a PhD in genetics. Long before we started writing papers together, Marion sent me evolutionary biology books to Israel, and when we met we discussed the many hot topics of","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42918750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental Epigenetics 2022 update","authors":"M. Skinner","doi":"10.1093/eep/dvac008","DOIUrl":"https://doi.org/10.1093/eep/dvac008","url":null,"abstract":"An Oxford University Press publication, ‘Environmental Epigenetics’, just initiated its eighth year of operations with this Volume 8 Issue 1. We are a 100% open access journal listed in PubMed Central, along with numerous other access sites. Environmental Epigenetics is in review to obtain an impact factor in 2022. Special issues have occurred each year, and we encourage requests for special issues in environmental epigenetics. Our Special Issues in 2021–22 were on Epigenetic Transgenerational Inheritance, Generational Toxicology, and Environmental Epigenetics and Evolution (https://academic.oup.com/eep/pages/special_issues). The amount and diversity of our published studies are increasing as the field of environmental epigenetics grows and expands. We are looking forward to another productive year and encourage you to consider submissions to ‘Environmental Epigenetics’.","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44305879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geospatiotemporal and causal inference study of cannabis and other drugs as risk factors for female breast cancer USA 2003-2017.","authors":"Albert Stuart Reece, Gary Kenneth Hulse","doi":"10.1093/eep/dvac006","DOIUrl":"10.1093/eep/dvac006","url":null,"abstract":"<p><p>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], <i>P</i> = 1.10 × 10^-15}. At 8 years lag cigarettes:cannabis [β-est. = 2660 (2150.4, 3169.3), <i>P</i> = 4.60 × 10^-22] and cannabis:alcoholism [β-est. = 7010 (5461.6, 8558.4), <i>P</i> = 1.80 × 10^-17] were significant in ipw-panel regression. Terms including cannabidiol [CBD; β-est. = 16.16 (0.39, 31.93), <i>P</i> = 0.446] and cannabigerol [CBG; β-est. = 6.23 (2.06, 10.39), <i>P</i> = 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), <i>P</i> = 1.87 × 10^-11; β-est. = 2.31 (1.65, 2.96), <i>P</i> = 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.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8978645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60653128","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":"Maternal tobacco smoke exposure is associated with increased DNA methylation at human metastable epialleles in infant cord blood.","authors":"Rashmi Joglekar, Carole Grenier, Cathrine Hoyo, Kate Hoffman, Susan K Murphy","doi":"10.1093/eep/dvac005","DOIUrl":"10.1093/eep/dvac005","url":null,"abstract":"<p><p>Metastable epialleles (MEs) are genomic regions that are stochastically methylated prior to germ layer specification and exhibit high interindividual but low intra-individual variability across tissues. ME methylation is vulnerable to environmental stressors, including diet. Tobacco smoke (TS) exposure during pregnancy is associated with adverse impacts on fetal health and maternal micronutrient levels as well as altered methylation. Our objective was to determine if maternal smoke exposure impacts methylation at MEs. Consistent with prior studies, we observed reductions in one-carbon pathway micronutrients with gestational TS exposure, including maternal folate (<i>P</i> = 0.02) and vitamins B6 (<i>P</i> = 0.05) and B12 (<i>P</i> = 0.007). We examined putative MEs <i>BOLA3, PAX8,</i> and <i>ZFYVE28</i> in cord blood specimens from 85 Newborn Epigenetics STudy participants. Gestational TS exposure was associated with elevated DNA methylation at <i>PAX8</i> (+5.22% average methylation; 95% CI: 0.33% to 10.10%; <i>P</i> = 0.037). In human conceptal kidney tissues, higher <i>PAX8</i> transcription was associated with lower methylation (<i>R</i> _s = 0.55; <i>P</i> = 0.07), suggesting that the methylation levels established at MEs, and their environmentally induced perturbation, may have meaningful, tissue-specific functional consequences. This may be particularly important because <i>PAX8</i> is implicated in several cancers, including pediatric kidney cancer. Our data are the first to indicate vulnerability of human ME methylation establishment to TS exposure, with a general trend of increasing levels of methylation at these loci. Further investigation is needed to determine how TS exposure-mediated changes in DNA methylation at MEs, and consequent expression levels, might affect smoking-related disease risk.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8962709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48510620","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}