Environmental Epigenetics最新文献

{"title":"Paternal transmission of behavioural and metabolic traits induced by postnatal stress to the 5th generation in mice.","authors":"Chiara Boscardin,&nbsp;Francesca Manuella,&nbsp;Isabelle M Mansuy","doi":"10.1093/eep/dvac024","DOIUrl":"https://doi.org/10.1093/eep/dvac024","url":null,"abstract":"<p><p>Life experiences and environmental conditions in childhood can change the physiology and behaviour of exposed individuals and, in some cases, of their offspring. In rodent models, stress/trauma, poor diet, and endocrine disruptors in a parent have been shown to cause phenotypes in the direct progeny, suggesting intergenerational inheritance. A few models also examined transmission to further offspring and suggested transgenerational inheritance, but such multigenerational inheritance is not well characterized. Our previous work on a mouse model of early postnatal stress showed that behaviour and metabolism are altered in the offspring of exposed males up to the 4th generation in the patriline and up to the 2nd generation in the matriline. The present study examined if symptoms can be transmitted beyond the 4th generation in the patriline. Analyses of the 5th and 6th generations of mice revealed that altered risk-taking and glucose regulation caused by postnatal stress are still manifested in the 5th generation but are attenuated in the 6th generation. Some of the symptoms are expressed in both males and females, but some are sex-dependent and sometimes opposite. These results indicate that postnatal trauma can affect behaviour and metabolism over many generations, suggesting epigenetic mechanisms of transmission.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"8 1","pages":"dvac024"},"PeriodicalIF":3.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/39/04/dvac024.PMC9730319.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10731082","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":"Accounting for transgenerational effects of toxicant exposure in population models alters the predicted long-term population status.","authors":"Susanne M Brander,&nbsp;J Wilson White,&nbsp;Bethany M DeCourten,&nbsp;Kaley Major,&nbsp;Sara J Hutton,&nbsp;Richard E Connon,&nbsp;Alvine Mehinto","doi":"10.1093/eep/dvac023","DOIUrl":"https://doi.org/10.1093/eep/dvac023","url":null,"abstract":"<p><p>Acute environmental stressors such as short-term exposure to pollutants can have lasting effects on organisms, potentially impacting future generations. Parental exposure to toxicants can result in changes to the epigenome (e.g., DNA methylation) that are passed down to subsequent, unexposed generations. However, it is difficult to gauge the cumulative population-scale impacts of epigenetic effects from laboratory experiments alone. Here, we developed a size- and age-structured delay-coordinate population model to evaluate the long-term consequences of epigenetic modifications on population sustainability. The model emulated changes in growth, mortality, and fecundity in the F0, F1, and F2 generations observed in experiments in which larval <i>Menidia beryllina</i> were exposed to environmentally relevant concentrations of bifenthrin (Bif), ethinylestradiol (EE2), levonorgestrel (LV), or trenbolone (TB) in the parent generation (F0) and reared in clean water up to the F2 generation. Our analysis suggests potentially dramatic population-level effects of repeated, chronic exposures of early-life stage fish that are not captured by models not accounting for those effects. Simulated exposures led to substantial declines in population abundance (LV and Bif) or near-extinction (EE2 and TB) with the exact trajectory and timeline of population decline dependent on the combination of F0, F1, and F2 effects produced by each compound. Even acute one-time exposures of each compound led to declines and recovery over multiple years due to lagged epigenetic effects. These results demonstrate the potential for environmentally relevant concentrations of commonly used compounds to impact the population dynamics and sustainability of an ecologically relevant species and model organism.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"8 1","pages":"dvac023"},"PeriodicalIF":3.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7a/60/dvac023.PMC9730329.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10712804","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":"Serum lead, mercury, manganese, and copper and DNA methylation age among adults in Detroit, Michigan.","authors":"Evans K Lodge,&nbsp;Radhika Dhingra,&nbsp;Chantel L Martin,&nbsp;Rebecca C Fry,&nbsp;Alexandra J White,&nbsp;Cavin K Ward-Caviness,&nbsp;Agaz H Wani,&nbsp;Monica Uddin,&nbsp;Derek E Wildman,&nbsp;Sandro Galea,&nbsp;Allison E Aiello","doi":"10.1093/eep/dvac018","DOIUrl":"https://doi.org/10.1093/eep/dvac018","url":null,"abstract":"<p><p>Although the effects of lead, mercury, manganese, and copper on individual disease processes are well understood, estimating the health effects of long-term exposure to these metals at the low concentrations often observed in the general population is difficult. In addition, the health effects of joint exposure to multiple metals are difficult to estimate. Biological aging refers to the integrative progression of multiple physiologic and molecular changes that make individuals more at risk of disease. Biomarkers of biological aging may be useful to estimate the population-level effects of metal exposure prior to the development of disease in the population. We used data from 290 participants in the Detroit Neighborhood Health Study to estimate the effect of serum lead, mercury, manganese, and copper on three DNA methylation-based biomarkers of biological aging (Horvath Age, PhenoAge, and GrimAge). We used mixed models and Bayesian kernel machine regression and controlled for participant sex, race, ethnicity, cigarette use, income, educational attainment, and block group poverty. We observed consistently positive estimates of the effects between lead and GrimAge acceleration and mercury and PhenoAge acceleration. In contrast, we observed consistently negative associations between manganese and PhenoAge acceleration and mercury and Horvath Age acceleration. We also observed curvilinear relationships between copper and both PhenoAge and GrimAge acceleration. Increasing total exposure to the observed mixture of metals was associated with increased PhenoAge and GrimAge acceleration and decreased Horvath Age acceleration. These findings indicate that an increase in serum lead or mercury from the 25th to 75th percentile is associated with a ∼0.25-year increase in two epigenetic markers of all-cause mortality in a population of adults in Detroit, Michigan. While few of the findings were statistically significant, their consistency and novelty warrant interest.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"8 1","pages":"dvac018"},"PeriodicalIF":3.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9620967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10751606","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":"Combined exposure to polychlorinated biphenyls and high-fat diet modifies the global epitranscriptomic landscape in mouse liver.","authors":"Carolyn M Klinge, Kellianne M Piell, Belinda J Petri, Liqing He, Xiang Zhang, Jianmin Pan, Shesh N Rai, Kalina Andreeva, Eric C Rouchka, Banrida Wahlang, Juliane I Beier, Matthew C Cave","doi":"10.1093/eep/dvab008","DOIUrl":"10.1093/eep/dvab008","url":null,"abstract":"<p><p>Exposure to a single dose of polychlorinated biphenyls (PCBs) and a 12-week high-fat diet (HFD) results in nonalcoholic steatohepatitis (NASH) in mice by altering intracellular signaling and inhibiting epidermal growth factor receptor signaling. Post-transcriptional chemical modification (PTM) of RNA regulates biological processes, but the contribution of epitranscriptomics to PCB-induced steatosis remains unknown. This study tested the hypothesis that PCB and HFD exposure alters the global RNA epitranscriptome in male mouse liver. C57BL/6J male mice were fed a HFD for 12 weeks and exposed to a single dose of Aroclor 1260 (20 mg/kg), PCB 126 (20 µg/kg), both Aroclor 1260 and PCB 126 or vehicle control after 2 weeks on HFD. Chemical RNA modifications were identified at the nucleoside level by liquid chromatography-mass spectrometry. From 22 PTM global RNA modifications, we identified 10 significant changes in RNA modifications in liver with HFD and PCB 126 exposure. Only two modifications were significantly different from HFD control liver in all three PCB exposure groups: 2'-O-methyladenosine (Am) and N(6)-methyladenosine (m6A). Exposure to HFD + PCB 126 + Aroclor 1260 increased the abundance of N(6), O(2)-dimethyladenosine (m6Am), which is associated with the largest number of transcript changes. Increased m6Am and pseudouridine were associated with increased protein expression of the writers of these modifications: Phosphorylated CTD Interacting Factor 1 (PCIF1) and Pseudouridine Synthase 10 (PUS10), respectively, in HFD + PCB 126- + Aroclor 1260-exposed mouse liver. Increased N1-methyladenosine (m1A) and m6A were associated with increased transcript levels of the readers of these modifications: YTH N6-Methyladenosine RNA Binding Protein 2 (YTHDF2), YTH Domain Containing 2 (YTHDC2), and reader FMRP Translational Regulator 1 (FMR1) transcript and protein abundance. The results demonstrate that PCB exposure alters the global epitranscriptome in a mouse model of NASH; however, the mechanism for these changes requires further investigation.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"7 1","pages":"dvab008"},"PeriodicalIF":3.8,"publicationDate":"2021-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9731720","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":"DNA methylation at birth potentially mediates the association between prenatal lead (Pb) exposure and infant neurodevelopmental outcomes.","authors":"Christine A Rygiel, Dana C Dolinoy, Kelly M Bakulski, Max T Aung, Wei Perng, Tamara R Jones, Maritsa Solano-González, Howard Hu, Martha M Tellez-Rojo, Lourdes Schnaas, Erika Marcela, Karen E Peterson, Jaclyn M Goodrich","doi":"10.1093/eep/dvab005","DOIUrl":"10.1093/eep/dvab005","url":null,"abstract":"<p><p>Early-life lead (Pb) exposure has been linked to adverse neurodevelopmental outcomes. Recent evidence has indicated a critical role of DNA methylation (DNAm) in cognition, and Pb exposure has also been shown to alter DNAm. However, it is unknown whether DNAm is part of the mechanism of Pb neurotoxicity. This longitudinal study investigated the associations between trimester-specific (T1, T2, and T3) maternal blood Pb concentrations, gene-specific DNAm in umbilical cord blood, and infant neurodevelopmental outcomes at 12 and 24 months of age (mental development index, psychomotor development index, and behavioral rating scale of orientation/engagement and emotional regulation) among 85 mother-infant pairs from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) study. In the mediation analysis for this pilot study, <i>P</i> < 0.1 was considered significant. DNAm at a locus in <i>CCSER1</i> (probe ID cg02901723) mediated the association between T2 Pb on 24-month orientation/engagement [indirect effect estimate 4.44, 95% confidence interval (-0.09, 10.68), <i>P</i> = 0.06] and emotional regulation [3.62 (-0.05, 8.69), <i>P</i> = 0.05]. Cg18515027 (<i>GCNT1</i>) DNAm mediated the association of T1 Pb [-4.94 (-10.6, -0.77), <i>P</i> = 0.01] and T2 Pb [-3.52 (-8.09, -0.36), <i>P</i> = 0.02] with 24-month EMOCI, but there was a positive indirect effect estimate between T2 Pb and 24-month psychomotor development index [1.25 (-0.11, 3.32), <i>P</i> = 0.09]. The indirect effect was significant for cg19703494 (<i>TRAPPC6A</i>) DNAm in the association between T2 Pb and 24-month mental development index [1.54 (0, 3.87), <i>P</i> = 0.05]. There was also an indirect effect of cg23280166 (<i>VPS11</i>) DNAm on T3 Pb and 24-month EMOCI [2.43 (-0.16, 6.38), <i>P</i> = 0.08]. These associations provide preliminary evidence for gene-specific DNAm as mediators between prenatal Pb and adverse cognitive outcomes in offspring.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"7 1","pages":"dvab005"},"PeriodicalIF":4.8,"publicationDate":"2021-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e2/35/dvab005.PMC8206046.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9177640","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":"Controlled human exposures to diesel exhaust: a human epigenome-wide experiment of target bronchial epithelial cells.","authors":"Andres Cardenas, Raj P Fadadu, Lars Van Der Laan, Cavin Ward-Caviness, Louis Granger, David Diaz-Sanchez, Robert B Devlin, Marie-Abèle Bind","doi":"10.1093/eep/dvab003","DOIUrl":"10.1093/eep/dvab003","url":null,"abstract":"<p><p>Diesel exhaust (DE) is a major contributor to ambient air pollution around the world. It is a known human carcinogen that targets the respiratory system and increases risk for many diseases, but there is limited research on the effects of DE exposure on the epigenome of human bronchial epithelial cells. Understanding the epigenetic impact of this environmental pollutant can elucidate biological mechanisms involved in the pathogenesis of harmful DE-related health effects. To estimate the causal effect of short-term DE exposure on the bronchial epithelial epigenome, we conducted a controlled single-blinded randomized crossover human experiment of exposure to DE and used bronchoscopy and Illumina 450K arrays for data collection and analysis, respectively. Of the 13 participants, 11 (85%) were male and 2 (15%) were female, and 12 (92%) were White and one (8%) was Hispanic; the mean age was 26 years (SD = 3.8 years). Eighty CpGs were differentially methylated, achieving the minimum possible exact <i>P</i>-value of <i>P </i>=<i> </i>2.44 × 10^-4 (<i>i.e.</i> 2/2¹³). In regional analyses, we found two differentially methylated regions (DMRs) annotated to the chromosome 5 open reading frame 63 genes (<i>C5orf63</i>; 7-CpGs) and unc-45 myosin chaperone A gene (<i>UNC45A</i>; 5-CpGs). Both DMRs showed increased DNA methylation after DE exposure. The average causal effects for the DMRs ranged from 1.5% to 6.0% increases in DNA methylation at individual CpGs. In conclusion, we found that short-term DE alters DNA methylation of genes in target bronchial epithelial cells, demonstrating epigenetic level effects of exposure that could be implicated in pulmonary pathologies.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"7 1","pages":"dvab003"},"PeriodicalIF":4.8,"publicationDate":"2021-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/61/54/dvab003.PMC8035831.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10294144","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":"Perinatal DEHP exposure induces sex- and tissue-specific DNA methylation changes in both juvenile and adult mice.","authors":"Siyu Liu,&nbsp;Kai Wang,&nbsp;Laurie K Svoboda,&nbsp;Christine A Rygiel,&nbsp;Kari Neier,&nbsp;Tamara R Jones,&nbsp;Raymond G Cavalcante,&nbsp;Justin A Colacino,&nbsp;Dana C Dolinoy,&nbsp;Maureen A Sartor","doi":"10.1093/eep/dvab004","DOIUrl":"https://doi.org/10.1093/eep/dvab004","url":null,"abstract":"<p><p>Di(2-ethylhexyl) phthalate (DEHP) is a type of phthalate plasticizer found in a variety of consumer products and poses a public health concern due to its metabolic and endocrine disruption activities. Dysregulation of epigenetic modifications, including DNA methylation, has been shown to be an important mechanism for the pathogenic effects of prenatal exposures, including phthalates. In this study, we used an established mouse model to study the effect of perinatal DEHP exposure on the DNA methylation profile in liver (a primary target tissue of DEHP) and blood (a common surrogate tissue) of both juvenile and adult mice. Despite exposure ceasing at 3 weeks of age (PND21), we identified thousands of sex-specific differential DNA methylation events in 5-month old mice, more than identified at PND21, both in blood and liver. Only a small number of these differentially methylated cytosines (DMCs) overlapped between the time points, or between tissues (i.e. liver and blood), indicating blood may not be an appropriate surrogate tissue to estimate the effects of DEHP exposure on liver DNA methylation. We detected sex-specific DMCs common between 3-week and 5-month samples, pointing to specific DNA methylation alterations that are consistent between weanling and adult mice. In summary, this is the first study to assess the genome-wide DNA methylation profiles in liver and blood at two different aged cohorts in response to perinatal DEHP exposure. Our findings cast light on the implications of using surrogate tissue instead of target tissue in human population-based studies and identify epigenetic biomarkers for DEHP exposure.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"7 1","pages":"dvab004"},"PeriodicalIF":3.8,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvab004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9544595","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":"Short- and long-term effects of perinatal phthalate exposures on metabolic pathways in the mouse liver.","authors":"Kari Neier, Luke Montrose, Kathleen Chen, Maureen A Malloy, Tamara R Jones, Laurie K Svoboda, Craig Harris, Peter X K Song, Subramaniam Pennathur, Maureen A Sartor, Dana C Dolinoy","doi":"10.1093/eep/dvaa017","DOIUrl":"10.1093/eep/dvaa017","url":null,"abstract":"<p><p>Phthalates have been demonstrated to interfere with metabolism, presumably by interacting with peroxisome proliferator-activated receptors (PPARs). However, mechanisms linking developmental phthalate exposures to long-term metabolic effects have not yet been elucidated. We investigated the hypothesis that developmental phthalate exposure has long-lasting impacts on PPAR target gene expression and DNA methylation to influence hepatic metabolic profiles across the life course. We utilized an established longitudinal mouse model of perinatal exposures to diethylhexyl phthalate and diisononyl phthalate, and a mixture of diethylhexyl phthalate+diisononyl phthalate. Exposure was through the diet and spanned from 2 weeks before mating until weaning at postnatal day 21 (PND21). Liver tissue was analyzed from the offspring of exposed and control mice at PND21 and in another cohort of exposed and control mice at 10 months of age. RNA-seq and pathway enrichment analyses indicated that acetyl-CoA metabolic processes were altered in diisononyl phthalate-exposed female livers at both PND21 and 10 months (FDR = 0.0018). Within the pathway, all 13 significant genes were potential PPAR target genes. Promoter DNA methylation was altered at three candidate genes, but persistent effects were only observed for <i>Fasn</i>. Targeted metabolomics indicated that phthalate-exposed females had decreased acetyl-CoA at PND21 and increased acetyl-CoA and acylcarnitines at 10 months. Together, our data suggested that perinatal phthalate exposures were associated with short- and long-term activation of PPAR target genes, which manifested as increased fatty acid production in early postnatal life and increased fatty acid oxidation in adulthood. This presents a novel molecular pathway linking developmental phthalate exposures and metabolic health outcomes.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"6 1","pages":"dvaa017"},"PeriodicalIF":3.8,"publicationDate":"2020-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38777160","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 environmental exposure to bisphenols and epigenome-wide DNA methylation in infant cord blood.","authors":"Carolyn F McCabe,&nbsp;Vasantha Padmanabhan,&nbsp;Dana C Dolinoy,&nbsp;Steven E Domino,&nbsp;Tamara R Jones,&nbsp;Kelly M Bakulski,&nbsp;Jaclyn M Goodrich","doi":"10.1093/eep/dvaa021","DOIUrl":"https://doi.org/10.1093/eep/dvaa021","url":null,"abstract":"<p><p>Maternal prenatal exposures, including bisphenol A (BPA), are associated with offspring's risk of disease later in life. Alterations in DNA methylation may be a mechanism through which altered prenatal conditions (e.g. maternal exposure to environmental toxicants) elicit this disease risk. In the Michigan Mother and Infant Pairs Cohort, maternal first-trimester urinary BPA, bisphenol F, and bisphenol S concentrations were tested for association with DNA methylation patterns in infant umbilical cord blood leukocytes (<i>N</i> = 69). We used the Illumina Infinium MethylationEPIC BeadChip to quantitatively evaluate DNA methylation across the epigenome; 822 020 probes passed pre-processing and quality checks. Single-site DNA methylation and bisphenol models were adjusted for infant sex, estimated cell-type proportions (determined using cell-type estimation algorithm), and batch as covariates. Thirty-eight CpG sites [false discovery rate (FDR) <0.05] were significantly associated with maternal BPA exposure. Increasing BPA concentrations were associated with lower DNA methylation at 87% of significant sites. BPA exposure associated DNA methylation sites were enriched for 38 pathways significant at FDR <0.05. The pathway or gene-set with the greatest odds of enrichment for differential methylation (FDR <0.05) was type I interferon receptor binding. This study provides a novel understanding of fetal response to maternal bisphenol exposure through epigenetic change.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"6 1","pages":"dvaa021"},"PeriodicalIF":3.8,"publicationDate":"2020-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38777164","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":"Epigenome-wide association study (EWAS) for potential transgenerational disease epigenetic biomarkers in sperm following ancestral exposure to the pesticide methoxychlor.","authors":"Eric E Nilsson,&nbsp;Jennifer L M Thorson,&nbsp;Millissia Ben Maamar,&nbsp;Daniel Beck,&nbsp;Michael K Skinner","doi":"10.1093/eep/dvaa020","DOIUrl":"https://doi.org/10.1093/eep/dvaa020","url":null,"abstract":"<p><p>Environmental exposures such as chemical toxicants can alter gene expression and disease susceptibility through epigenetic processes. Epigenetic changes can be passed to future generations through germ cells through epigenetic transgenerational inheritance of increased disease susceptibility. The current study used an epigenome-wide association study (EWAS) to investigate whether specific transgenerational epigenetic signatures of differential DNA methylation regions (DMRs) exist that are associated with particular disease states in the F3 generation great-grand offspring of F0 generation rats exposed during gestation to the agricultural pesticide methoxychlor. The transgenerational epigenetic profiles of sperm from F3 generation methoxychlor lineage rats that have only one disease state were compared to those that have no disease. Observations identify disease specific patterns of DMRs for these transgenerational rats that can potentially serve as epigenetic biomarkers for prostate disease, kidney disease, obesity, and the presence of multiple diseases. The chromosomal locations, genomic features, and gene associations of the DMRs are characterized. Disease specific DMR sets contained DMR-associated genes that have previously been shown to be associated with that specific disease. Future epigenetic biomarkers could potentially be developed and validated for humans as a disease susceptibility diagnostic tool to facilitate preventative medicine and management of disease.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"6 1","pages":"dvaa020"},"PeriodicalIF":3.8,"publicationDate":"2020-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d7/83/dvaa020.PMC7757123.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38777161","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}