Environmental Epigenetics最新文献

{"title":"Effect of concentration and duration of particulate matter exposure on the transcriptome and DNA methylome of bronchial epithelial cells.","authors":"Steven K Huang,&nbsp;Priya Tripathi,&nbsp;Lada A Koneva,&nbsp;Raymond G Cavalcante,&nbsp;Nathan Craig,&nbsp;Anne M Scruggs,&nbsp;Maureen A Sartor,&nbsp;Furong Deng,&nbsp;Yahong Chen","doi":"10.1093/eep/dvaa022","DOIUrl":"https://doi.org/10.1093/eep/dvaa022","url":null,"abstract":"<p><p>Exposure to particulate matter (PM) from ambient air pollution is a well-known risk factor for many lung diseases, but the mechanism(s) for this is not completely understood. Bronchial epithelial cells, which line the airway of the respiratory tract, undergo genome-wide level changes in gene expression and DNA methylation particularly when exposed to fine (<2.5 µm) PM (PM_2.5). Although some of these changes have been reported in other studies, a comparison of how different concentrations and duration of exposure affect both the gene transcriptome and DNA methylome has not been done. Here, we exposed BEAS-2B, a bronchial epithelial cell line, to different concentrations of PM_2.5, and compared how single or repeated doses of PM_2.5 affect both the transcriptome and methylome of cells. Widespread changes in gene expression occurred after cells were exposed to a single treatment of high-concentration (30 µg/cm²) PM_2.5 for 24 h. These genes were enriched in pathways regulating cytokine-cytokine interactions, Mitogen-Activated Protein Kinase (MAPK) signaling, PI3K-Akt signaling, IL6, and P53. DNA methylomic analysis showed that nearly half of the differentially expressed genes were found to also have DNA methylation changes, with just a slightly greater trend toward overall hypomethylation across the genome. Cells exposed to a lower concentration (1 µg/cm²) of PM_2.5 demonstrated a comparable, but more attenuated change in gene expression compared to cells exposed to higher concentrations. There were also many genes affected by lower concentrations of PM_2.5, but not higher concentrations. Additionally, repeated exposure to PM_2.5 (1 µg/cm²) for seven days resulted in transcriptomic and DNA methylomic changes that were distinct from cells treated with PM_2.5 for only one day. Compared to single exposure, repeated exposure to PM_2.5 caused a more notable degree of hypomethylation across the genome, though certain genes and regions demonstrated increased DNA methylation. The overall increase in hypomethylation, especially with repeated exposure to PM_2.5, was associated with an increase in expression of ten-eleven translocation enzymes. These data demonstrate how variations in concentration and duration of PM_2.5 exposure induce distinct differences in the transcriptomic and DNA methylomic profile of bronchial epithelial cells, which may have important implications in the development of both acute and chronic lung disease.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":" ","pages":"dvaa022"},"PeriodicalIF":3.8,"publicationDate":"2021-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25456841","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}

{"title":"Prenatal lead exposure and cord blood DNA methylation in PROGRESS: an epigenome-wide association study.","authors":"Jonathan A Heiss,&nbsp;Martha M Téllez-Rojo,&nbsp;Guadalupe Estrada-Gutiérrez,&nbsp;Lourdes Schnaas,&nbsp;Chitra Amarasiriwardena,&nbsp;Andrea A Baccarelli,&nbsp;Robert O Wright,&nbsp;Allan C Just","doi":"10.1093/eep/dvaa014","DOIUrl":"https://doi.org/10.1093/eep/dvaa014","url":null,"abstract":"<p><p>The effects of prenatal lead exposure on child development include impaired growth and cognitive function. DNA methylation might be involved in the underlying mechanisms and previous epigenome-wide association studies reported associations between lead exposure during pregnancy and cord blood methylation levels. However, it is unclear during which developmental stage lead exposure is most harmful. Cord blood methylation levels were assayed in 420 children from a Mexican pre-birth cohort using the Illumina Infinium MethylationEPIC microarray. Lead concentrations were measured in umbilical cord blood as well as in blood samples from the mothers collected at 2nd and 3rd trimester and delivery using inductively coupled plasma-mass spectrometry. In addition, maternal bone lead levels were measured in tibia and patella using X-ray fluorescence. Comprehensive quality control and preprocessing of microarray data was followed by an unbiased restriction to methylation sites with substantial variance. Methylation levels at 202 111 cytosine-phosphate-guanine sites were regressed on each exposure adjusting for child sex, leukocyte composition, batch variables, gestational age, birthweight-for-gestational-age, maternal age, maternal education and mode of delivery. We find no association between prenatal lead exposure and cord blood methylation. This null result is strengthened by a sensitivity analysis showing that in the same dataset known biomarkers for birthweight-for-gestational-age can be recovered and the fact that phenotypic associations with lead exposure have been described in the same cohort.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"6 1","pages":"dvaa014"},"PeriodicalIF":3.8,"publicationDate":"2020-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38716576","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":"Metabolic diseases affect male reproduction and induce signatures in gametes that may compromise the offspring health.","authors":"Sara C Pereira, Luís Crisóstomo, Mário Sousa, Pedro F Oliveira, Marco G Alves","doi":"10.1093/eep/dvaa019","DOIUrl":"10.1093/eep/dvaa019","url":null,"abstract":"<p><p>The most prevalent diseases worldwide are non-communicable such as obesity and type 2 diabetes. Noteworthy, the prevalence of obesity and type 2 diabetes is expected to steadily increase in the next decades, mostly fueled by bad feeding habits, stress, and sedentarism. The reproductive function of individuals is severely affected by abnormal metabolic environments, both at mechanical and biochemical levels. Along with mechanical dysfunctions, and decreased sperm quality (promoted both directly and indirectly by metabolic abnormalities), several studies have already reported the potentially harmful effects of metabolic disorders in the genetic and epigenetic cargo of spermatozoa, and the epigenetic inheritance of molecular signatures induced by metabolic profile (paternal diet, obesity, and diabetes). The inheritance of epigenetic factors towards the development of metabolic abnormalities means that more people in reproductive age can potentially suffer from these disorders and for longer periods. In its turn, these individuals can also transmit this (epi)genetic information to future generations, creating a vicious cycle. In this review, we collect the reported harmful effects related to acquired metabolic disorders and diet in sperm parameters and male reproductive potential. Besides, we will discuss the novel findings regarding paternal epigenetic inheritance, particularly the ones induced by paternal diet rich in fats, obesity, and type 2 diabetes. We analyze the data attained with <i>in vitro</i> and animal models as well as in long-term transgenerational population studies. Although the findings on this topic are very recent, epigenetic inheritance of metabolic disease has a huge societal impact, which may be crucial to tackle the 'fat epidemic' efficiently.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"6 1","pages":"dvaa019"},"PeriodicalIF":3.8,"publicationDate":"2020-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38716581","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":"Differential susceptibility to endocrine disruptor-induced epimutagenesis.","authors":"Jake D Lehle, John R McCarrey","doi":"10.1093/eep/dvaa016","DOIUrl":"10.1093/eep/dvaa016","url":null,"abstract":"<p><p>There is now considerable evidence indicating the potential for endocrine disrupting chemicals to alter the epigenome and for subsets of these epigenomic changes or \"epimutations\" to be heritably transmitted to offspring in subsequent generations. While there have been many studies indicating how exposure to endocrine disrupting chemicals can disrupt various organs associated with the body's endocrine systems, there is relatively limited information regarding the relative susceptibility of different specific organs, tissues, or cell types to endocrine disrupting chemical-induced epimutagenesis. Here we review available information about different organs, tissues, cell types, and/or cell lines which have been shown to be susceptible to specific endocrine disrupting chemical-induced epimutations. In addition, we discuss possible mechanisms that may be involved, or impacted by this tissue- or cell type-specific, differential susceptibility to different endocrine disrupting chemicals. Finally, we summarize available information indicating that certain periods of development display elevated susceptibility to endocrine disrupting chemical exposure and we describe how this may affect the extent to which germline epimutations can be transmitted inter- or transgenerationally. We conclude that cell type-specific differential susceptibility to endocrine disrupting chemical-induced epimutagenesis is likely to directly impact the extent to, or manner in, which endocrine disrupting chemical exposure initially induces epigenetic changes to DNA methylation and/or histone modifications, and how these endocrine disrupting chemical-induced epimutations can then subsequently impact gene expression, potentially leading to the development of heritable disease states.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"6 1","pages":"dvaa016"},"PeriodicalIF":4.8,"publicationDate":"2020-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9f/03/dvaa016.PMC7722801.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38716578","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":"Communicating science: epigenetics in the spotlight.","authors":"Stephanie O M Dyke,&nbsp;Catherine A Ennis,&nbsp;Yann Joly,&nbsp;Jörn Walter,&nbsp;Reiner Siebert,&nbsp;Tomi Pastinen","doi":"10.1093/eep/dvaa015","DOIUrl":"https://doi.org/10.1093/eep/dvaa015","url":null,"abstract":"<p><p>Given the public interest in epigenetic science, this study aimed to better understand media representations of epigenetics in national newspaper coverage in various regions in North America, Europe, and Asia. Content analysis was used to study media messages about epigenetics, their policy focus, and the balance of the reporting. We identified several recurring themes in the news reports, including policy messages relating to individual and societal responsibilities. We also found shortcomings in the media's portrayal of epigenetic science, and sought to identify potential causes by considering the underlying scientific evidence that the media reported on. A case study analysis showed that the results of epigenetic studies were often overstated in academic research publications due to common experimental limitations. We suggest that defining standardized criteria with which to evaluate epigenetic studies could help to overcome some of the challenges inherent in translating complex epigenetic research findings for non-technical audiences, and present a Press Kit template that researchers can adapt and use to aid in the development of accurate and balanced press releases.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"6 1","pages":"dvaa015"},"PeriodicalIF":3.8,"publicationDate":"2020-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38642804","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 mothers' early life exposure to low or high folate on progeny outcome and DNA methylation patterns.","authors":"Lundi Ly,&nbsp;Donovan Chan,&nbsp;Mylène Landry,&nbsp;Camille Angle,&nbsp;Josée Martel,&nbsp;Jacquetta Trasler","doi":"10.1093/eep/dvaa018","DOIUrl":"https://doi.org/10.1093/eep/dvaa018","url":null,"abstract":"<p><p>The dynamic patterning of DNA and histone methylation during oocyte development presents a potentially susceptible time for epigenetic disruption due to early life environmental exposure of future mothers. We investigated whether maternal exposure to folic acid deficient and supplemented diets starting <i>in utero</i> could affect oocytes and cause adverse developmental and epigenetic effects in next generation progeny. Female BALB/c mice (F0) were placed on one of four amino acid defined diets for 4 weeks before pregnancy and throughout gestation and lactation: folic acid control (rodent recommended daily intake; Ctrl), 7-fold folic acid deficient, 10-fold folic acid supplemented or 20-fold folic acid supplemented diets. F1 female pups were weaned onto Ctrl diets, mated to produce the F2 generation and the F2 offspring were examined at E18.5 for developmental and epigenetic abnormalities. Resorption rates were increased and litter sizes decreased amongst F2 E18.5-day litters in the 20-fold folic acid supplemented group. Increases in abnormal embryo outcomes were observed in all three folic acid deficient and supplemented groups. Subtle genome-wide DNA methylation alterations were found in the placentas and brains of F2 offspring in the 7-fold folic acid deficient , 10-fold folic acid supplemented and 20-fold folic acid supplemented groups; in contrast, global and imprinted gene methylation were not affected. The findings show that early life female environmental exposures to both low and high folate prior to oocyte maturation can compromise oocyte quality, adversely affecting offspring of the next generation, in part by altering DNA methylation patterns.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"6 1","pages":"dvaa018"},"PeriodicalIF":3.8,"publicationDate":"2020-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38642805","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}