Environmental Epigenetics最新文献

{"title":"Epigenetics in the public sphere: interdisciplinary perspectives","authors":"M. Dubois, S. Louvel, A. Le Goff, Catherine Guaspare, P. Allard","doi":"10.1093/eep/dvz019","DOIUrl":"https://doi.org/10.1093/eep/dvz019","url":null,"abstract":"Abstract Despite the high public interest in epigenetics, few scholars have empirically investigated the forms, reasons and consequences of the public circulation of epigenetics. Using an original database focusing on ‘lifestyle’ or ‘everyday’ epigenetics, this article aims to promote an open-minded and interdisciplinary dialogue between the public appropriation of epigenetics and the current scientific state of the art. It raises three main questions: Are there any specific modes of circulation of epigenetics in the general public? Why does epigenetics seem so appealing to the public? Within the public repertoire of epigenetics, is it possible to identify some specific knowledge claims and, if so, given the current state of the art, what is their degree of accuracy? The article argues that the social diffusion of epigenetics frequently carries on beliefs and misconceptions about genetics and epigenetics. The social life of epigenetics fuels a collective ‘illusion’ of control and empowerment on the basis of which new markets expand. More unexpectedly, this article underlines the emergence of a new scientific culture, i.e. the ‘scientifization’ of the cultural appropriation of epigenetics. Our analysis can inform the scientific community about the current and evolving state of the public representation of epigenetics and help it frame outreach activities.","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvz019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46802125","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":"Cadmium exposure and <i>MEG3</i> methylation differences between Whites and African Americans in the NEST Cohort.","authors":"John S House,&nbsp;Jonathan Hall,&nbsp;Sarah S Park,&nbsp;Antonio Planchart,&nbsp;Eric Money,&nbsp;Rachel L Maguire,&nbsp;Zhiqing Huang,&nbsp;Carolyn J Mattingly,&nbsp;David Skaar,&nbsp;Jung Ying Tzeng,&nbsp;Thomas H Darrah,&nbsp;Avner Vengosh,&nbsp;Susan K Murphy,&nbsp;Randy L Jirtle,&nbsp;Cathrine Hoyo","doi":"10.1093/eep/dvz014","DOIUrl":"https://doi.org/10.1093/eep/dvz014","url":null,"abstract":"<p><p>Cadmium (Cd) is a ubiquitous environmental pollutant associated with a wide range of health outcomes including cancer. However, obscure exposure sources often hinder prevention efforts. Further, although epigenetic mechanisms are suspected to link these associations, gene sequence regions targeted by Cd are unclear. Aberrant methylation of a differentially methylated region (DMR) on the <i>MEG3</i> gene that regulates the expression of a cluster of genes including <i>MEG3, DLK1, MEG8, MEG9</i> and <i>DIO3</i> has been associated with multiple cancers. In 287 infant-mother pairs, we used a combination of linear regression and the Getis-Ord Gi* statistic to determine if maternal blood Cd concentrations were associated with offspring CpG methylation of the sequence region regulating a cluster of imprinted genes including <i>MEG3</i>. Correlations were used to examine potential sources and routes. We observed a significant geographic co-clustering of elevated prenatal Cd levels and <i>MEG3</i> DMR hypermethylation in cord blood (<i>P</i> = 0.01), and these findings were substantiated in our statistical models (β = 1.70, se = 0.80, <i>P</i> = 0.03). These associations were strongest in those born to African American women (β = 3.52, se = 1.32, <i>P</i> = 0.01) compared with those born to White women (β = 1.24, se = 2.11, <i>P</i> = 0.56) or Hispanic women (β = 1.18, se = 1.24, <i>P</i> = 0.34). Consistent with Cd bioaccumulation during the life course, blood Cd levels increased with age (β = 0.015 µg/dl/year, <i>P</i> = 0.003), and Cd concentrations were significantly correlated between blood and urine (ρ > 0.47, <i>P</i> < 0.01), but not hand wipe, soil or house dust concentrations (<i>P</i> > 0.05). Together, these data support that prenatal Cd exposure is associated with aberrant methylation of the imprint regulatory element for the <i>MEG3</i> gene cluster at birth. However, neither house-dust nor water are likely exposure sources, and ingestion via contaminated hands is also unlikely to be a significant exposure route in this population. Larger studies are required to identify routes and sources of exposure.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"5 3","pages":"dvz014"},"PeriodicalIF":3.8,"publicationDate":"2019-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvz014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41195480","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":"Epigenetic transgenerational inheritance of testis pathology and Sertoli cell epimutations: generational origins of male infertility.","authors":"Ingrid Sadler-Riggleman, Rachel Klukovich, Eric Nilsson, Daniel Beck, Yeming Xie, Wei Yan, Michael K Skinner","doi":"10.1093/eep/dvz013","DOIUrl":"10.1093/eep/dvz013","url":null,"abstract":"<p><p>Male reproductive health has been in decline for decades with dropping sperm counts and increasing infertility, which has created a significant societal and economic burden. Between the 1970s and now, a general decline of over 50% in sperm concentration has been observed in the population. Environmental toxicant-induced epigenetic transgenerational inheritance has been shown to affect testis pathology and sperm count. Sertoli cells have an essential role in spermatogenesis by providing physical and nutritional support for developing germ cells. The current study was designed to further investigate the transgenerational epigenetic changes in the rat Sertoli cell epigenome and transcriptome that are associated with the onset of testis disease. Gestating female F0 generation rats were transiently exposed during the period of fetal gonadal sex determination to the environmental toxicants, such as dichlorodiphenyltrichloroethane (DDT) or vinclozolin. The F1 generation offspring were bred (i.e. intercross within the lineage) to produce the F2 generation grand-offspring that were then bred to produce the transgenerational F3 generation (i.e. great-grand-offspring) with no sibling or cousin breeding used. The focus of the current study was to investigate the transgenerational testis disease etiology, so F3 generation rats were utilized. The DNA and RNA were obtained from purified Sertoli cells isolated from postnatal 20-day-old male testis of F3 generation rats. Transgenerational alterations in DNA methylation, noncoding RNA, and gene expression were observed in the Sertoli cells from vinclozolin and DDT lineages when compared to the control (vehicle exposed) lineage. Genes associated with abnormal Sertoli cell function and testis pathology were identified, and the transgenerational impacts of vinclozolin and DDT were determined. Alterations in critical gene pathways, such as the pyruvate metabolism pathway, were identified. Observations suggest that ancestral exposures to environmental toxicants promote the epigenetic transgenerational inheritance of Sertoli cell epigenetic and transcriptome alterations that associate with testis abnormalities. These epigenetic alterations appear to be critical factors in the developmental and generational origins of testis pathologies and male infertility.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"5 3","pages":"dvz013"},"PeriodicalIF":4.8,"publicationDate":"2019-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/22/ec/dvz013.PMC6736068.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41195481","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":"A gene regulatory network for Müllerian duct regression.","authors":"Malcolm M Moses,&nbsp;Richard R Behringer","doi":"10.1093/eep/dvz017","DOIUrl":"https://doi.org/10.1093/eep/dvz017","url":null,"abstract":"<p><p>Mammalian embryos initially develop progenitor tissues for both male and female reproductive tract organs, known as the Wolffian ducts and the Müllerian ducts, respectively. Ultimately, each individual develops a single set of male or female reproductive tract organs. Therefore, an essential step for sex differentiation is the regression of one duct and growth and differentiation of the other duct. In males, this requires Müllerian duct regression and Wolffian duct growth and differentiation. Müllerian duct regression is induced by the expression of <i>Amh</i>, encoding anti-Müllerian hormone, from the fetal testes. Subsequently, receptor-mediated signal transduction in mesenchymal cells surrounding the Müllerian duct epithelium leads to duct elimination. The genes that induce <i>Amh</i> transcription and the downstream signaling that results from <i>Amh</i> activity form a pathway. However, the molecular details of this pathway are currently unknown. A set of essential genes for AMH pathway function has been identified. More recently, transcriptome analysis of male and female Müllerian duct mesenchyme at an initial stage of regression has identified new genes that may mediate elimination of the Müllerian system. The evidence taken together can be used to generate an initial gene regulatory network describing the <i>Amh</i> pathway for Müllerian duct regression. An <i>Amh</i> gene regulatory network will be a useful tool to study Müllerian duct regression, sex differentiation, and its relationship to environmental influences.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"5 3","pages":"dvz017"},"PeriodicalIF":3.8,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvz017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9730852","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":"Estrogen receptor 1 expression and methylation of Esr1 promoter in mouse fetal prostate mesenchymal cells induced by gestational exposure to bisphenol A or ethinylestradiol","authors":"R. Bhandari, Julia A. Taylor, Jennifer Sommerfeld-Sager, D. Tillitt, W. Ricke, F. V. vom Saal","doi":"10.1093/eep/dvz012","DOIUrl":"https://doi.org/10.1093/eep/dvz012","url":null,"abstract":"Abstract Fetal/neonatal environmental estrogen exposures alter developmental programing of the prostate gland causing onset of diseases later in life. We have previously shown in vitro that exposures to 17β-estradiol (E2) and the endocrine disrupting chemical bisphenol A, at concentrations relevant to human exposure, cause an elevation of estrogen receptor α (Esr1) mRNA in primary cultures of fetal mouse prostate mesenchymal cells; a similar result was observed in the fetal rat urogenital sinus. Effects of these chemicals on prostate mesenchyme in vivo are not well understood. Here we show effects in mice of fetal exposure to the estrogenic drug in mixed oral contraceptives, 17α-ethinylestradiol (EE2), at a concentration of EE2 encountered by human embryos/fetuses whose mothers become pregnant while on EE2-containing oral contraceptives, or bisphenol A at a concentration relevant to exposures observed in human fetuses in vivo. Expression of Esr1 was elevated by bisphenol A or EE2 exposures, which decreased the global expression of DNA methyltransferase 3A (Dnmt3a), while methylation of Esr1 promoter was significantly increased. These results show that exposures to the environmental estrogen bisphenol A and drug EE2 cause transcriptional and epigenetic alterations to expression of estrogen receptors in developing prostate mesenchyme in vivo.","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvz012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49428611","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":"Epigenetic, transcriptional and phenotypic responses in two generations of Daphnia magna exposed to the DNA methylation inhibitor 5-azacytidine","authors":"L. Lindeman, J. Thaulow, You Song, J. Kamstra, Li Xie, J. Asselman, P. Aleström, K. Tollefsen","doi":"10.1093/eep/dvz016","DOIUrl":"https://doi.org/10.1093/eep/dvz016","url":null,"abstract":"Abstract The water flea Daphnia magna is a keystone species in freshwater ecosystems and has been widely used as a model organism in environmental ecotoxicology. This aquatic crustacean is sensitive to environmental stressors and displays considerable plasticity in adapting to changing environmental conditions. Part of this plasticity may be due to epigenetic regulation of gene expression, including changes to DNA methylation and histone modifications. Because of the generally hypomethylated genome of this species, we hypothesized that the histone code may have an essential role in the epigenetic control and that histone modifications might be an early marker for stress. This study aims to characterize the epigenetic, transcriptional and phenotypic responses and their causal linkages in directly exposed adult (F0) Daphnia and peritoneal exposed neonates (F1) after a chronic (7-day) exposure to a sublethal concentration (10 mg/l) of 5-azacytidine, a well-studied vertebrate DNA methylation inhibitor. Exposure of the F0 generation significantly reduced the cumulative fecundity, accompanied with differential expression of genes in the one-carbon-cycle metabolic pathway. In the epigenome of the F0 generation, a decrease in global DNA methylation, but no significant changes on H3K4me3 or H3K27me3, were observed. In the F1 offspring generation, changes in gene expression, a significant reduction in global DNA methylation and changes in histone modifications were identified. The results indicate that exposure during adulthood may result in more pronounced effects on early development in the offspring generation, though interpretation of the data should be carefully done since both the exposure regime and developmental period is different in the two generations examined. The obtained results improve our understanding of crustacean epigenetics and the tools developed may promote use of epigenetic markers in hazard assessment of environmental stressors.","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvz016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49058588","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":"Potential (mis)use of epigenetic age estimators by private companies and public agencies: human rights law should provide ethical guidance","authors":"C. Dupras, S. Beck, M. Rothstein, A. Berner, Katie M. Saulnier, Miriam Pinkesz, A. Prince, Stamatina Liosi, Lingqiao Song, Y. Joly","doi":"10.1093/EEP/DVZ018","DOIUrl":"https://doi.org/10.1093/EEP/DVZ018","url":null,"abstract":"","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41579254","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":"Three-dimensional testicular organoids as novel in vitro models of testicular biology and toxicology","authors":"S. Sakib, A. Voigt, T. Goldsmith, I. Dobrinski","doi":"10.1093/eep/dvz011","DOIUrl":"https://doi.org/10.1093/eep/dvz011","url":null,"abstract":"Abstract Organoids are three dimensional structures consisting of multiple cell types that recapitulate the cellular architecture and functionality of native organs. Over the last decade, the advent of organoid research has opened up many avenues for basic and translational studies. Following suit of other disciplines, research groups working in the field of male reproductive biology have started establishing and characterizing testicular organoids. The three-dimensional architectural and functional similarities of organoids to their tissue of origin facilitate study of complex cell interactions, tissue development and establishment of representative, scalable models for drug and toxicity screening. In this review, we discuss the current state of testicular organoid research, their advantages over conventional monolayer culture and their potential applications in the field of reproductive biology and toxicology.","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvz011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47656991","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":"Early postnatal overnutrition accelerates aging-associated epigenetic drift in pancreatic islets","authors":"Ge Li, T. D. Petkova, Eleonora Laritsky, Noah J. Kessler, Maria S. Baker, Shaoyu Zhu, R. Waterland","doi":"10.1093/eep/dvz015","DOIUrl":"https://doi.org/10.1093/eep/dvz015","url":null,"abstract":"Abstract Pancreatic islets of type 2 diabetes patients have altered DNA methylation, contributing to islet dysfunction and the onset of type 2 diabetes. The cause of these epigenetic alterations is largely unknown. We set out to test whether (i) islet DNA methylation would change with aging and (ii) early postnatal overnutrition would persistently alter DNA methylation. We performed genome-scale DNA methylation profiling in islets from postnatally over-nourished (suckled in a small litter) and control male mice at both postnatal day 21 and postnatal day 180. DNA methylation differences were validated using quantitative bisulfite pyrosequencing, and associations with expression were assessed by RT-PCR. We discovered that genomic regions that are hypermethylated in exocrine relative to endocrine pancreas tend to gain methylation in islets during aging (R2 = 0.33, P < 0.0001). These methylation differences were inversely correlated with mRNA expression of genes relevant to β cell function [including Rab3b (Ras-related protein Rab-3B), Cacnb3 (voltage-dependent L-type calcium channel subunit 3), Atp2a3 (sarcoplasmic/endoplasmic reticulum calcium ATPase 3) and Ins2 (insulin 2)]. Relative to control, small litter islets showed DNA methylation differences directly after weaning and in adulthood, but few of these were present at both ages. Surprisingly, we found substantial overlap of methylated loci caused by aging and small litter feeding, suggesting that the age-associated gain of DNA methylation happened much earlier in small litter islets than control islets. Our results provide the novel insights that aging-associated DNA methylation increases reflect an epigenetic drift toward the exocrine pancreas epigenome, and that early postnatal overnutrition may accelerate this process.","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvz015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46378383","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":"Tissue-specific changes in <i>Srebf1</i> and <i>Srebf2</i> expression and DNA methylation with perinatal phthalate exposure.","authors":"Laura Moody,&nbsp;Diego Hernández-Saavedra,&nbsp;Daniel G Kougias,&nbsp;Hong Chen,&nbsp;Janice M Juraska,&nbsp;Yuan-Xiang Pan","doi":"10.1093/eep/dvz009","DOIUrl":"https://doi.org/10.1093/eep/dvz009","url":null,"abstract":"<p><p>Perinatal exposure to endocrine disrupting chemicals negatively impacts health, but the mechanism by which such toxicants damage long-term reproductive and metabolic function is unknown. Lipid metabolism plays a pivotal role in steroid hormone synthesis as well as energy utilization and storage; thus, aberrant lipid regulation may contribute to phthalate-driven health impairments. In order to test this hypothesis, we specifically examined epigenetic disruptions in lipid metabolism pathways after perinatal phthalate exposure. During gestation and lactation, pregnant Long-Evans rat dams were fed environmentally relevant doses of phthalate mixture: 0 (CON), 200 (LO), or 1000 (HI) µg/kg body weight/day. On PND90, male offspring in the LO and HI groups had higher body weights than CON rats. Gene expression of lipid metabolism pathways was altered in testis and adipose tissue of males exposed to the HI phthalate dosage. Specifically, <i>Srebf1</i> was downregulated in testis and <i>Srebf2</i> was upregulated in adipose tissue. In testis of HI rats, DNA methylation was increased at two loci and reduced at one other site surrounding <i>Srebf1</i> transcription start site. In adipose tissue of HI rats, we observed increased DNA methylation at one region within the first intron of <i>Srebf2</i>. Computational analysis revealed several potential transcriptional regulator binding sites, suggesting functional relevance of the identified differentially methylated CpGs. Overall, we show that perinatal phthalate exposure affects lipid metabolism gene expression in a tissue-specific manner possibly through altering DNA methylation of <i>Srebf1</i> and <i>Srebf2</i>.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"5 2","pages":"dvz009"},"PeriodicalIF":3.8,"publicationDate":"2019-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvz009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37365416","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}