Environmental Epigenetics最新文献

{"title":"Folic acid supplementation reduces multigenerational sperm miRNA perturbation induced by <i>in utero</i> environmental contaminant exposure.","authors":"P M Herst,&nbsp;M Dalvai,&nbsp;M Lessard,&nbsp;P L Charest,&nbsp;P Navarro,&nbsp;C Joly-Beauparlant,&nbsp;A Droit,&nbsp;J M Trasler,&nbsp;S Kimmins,&nbsp;A J MacFarlane,&nbsp;M-O Benoit-Biancamano,&nbsp;J L Bailey","doi":"10.1093/eep/dvz024","DOIUrl":"https://doi.org/10.1093/eep/dvz024","url":null,"abstract":"<p><p>Persistent organic pollutants (POPs) can induce epigenetic changes in the paternal germline. Here, we report that folic acid (FA) supplementation mitigates sperm miRNA profiles transgenerationally following <i>in utero</i> paternal exposure to POPs in a rat model. Pregnant founder dams were exposed to an environmentally relevant POPs mixture (or corn oil) ± FA supplementation and subsequent F1-F4 male descendants were not exposed to POPs and were fed the FA control diet. Sperm miRNA profiles of intergenerational (F1, F2) and transgenerational (F3, F4) lineages were investigated using miRNA deep sequencing. Across the F1-F4 generations, sperm miRNA profiles were less perturbed with POPs+FA compared to sperm from descendants of dams treated with POPs alone. POPs exposure consistently led to alteration of three sperm miRNAs across two generations, and similarly one sperm miRNA due to POPs+FA; which was in common with one POPs intergenerationally altered sperm miRNA. The sperm miRNAs that were affected by POPs alone are known to target genes involved in mammary gland and embryonic organ development in F1, sex differentiation and reproductive system development in F2 and cognition and brain development in F3. When the POPs treatment was combined with FA supplementation, however, these same miRNA-targeted gene pathways were perturbed to a lesser extend and only in F1 sperm. These findings suggest that FA partially mitigates the effect of POPs on paternally derived miRNA in a intergenerational manner.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"5 4","pages":"dvz024"},"PeriodicalIF":3.8,"publicationDate":"2019-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvz024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37471496","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 of father's smoking with offspring DNA methylation: a hypothesis-generating study.","authors":"G T Mørkve Knudsen,&nbsp;F I Rezwan,&nbsp;A Johannessen,&nbsp;S M Skulstad,&nbsp;R J Bertelsen,&nbsp;F G Real,&nbsp;S Krauss-Etschmann,&nbsp;V Patil,&nbsp;D Jarvis,&nbsp;S H Arshad,&nbsp;J W Holloway,&nbsp;C Svanes","doi":"10.1093/eep/dvz023","DOIUrl":"https://doi.org/10.1093/eep/dvz023","url":null,"abstract":"<p><p>Epidemiological studies suggest that father's smoking might influence their future children's health, but few studies have addressed whether paternal line effects might be related to altered DNA methylation patterns in the offspring. To investigate a potential association between fathers' smoking exposures and offspring DNA methylation using epigenome-wide association studies. We used data from 195 males and females (11-54 years) participating in two population-based cohorts. DNA methylation was quantified in whole blood using Illumina Infinium MethylationEPIC Beadchip. Comb-p was used to analyse differentially methylated regions (DMRs). Robust multivariate linear models, adjusted for personal/maternal smoking and cell-type proportion, were used to analyse offspring differentially associated probes (DMPs) related to paternal smoking. In sensitivity analyses, we adjusted for socio-economic position and clustering by family. Adjustment for inflation was based on estimation of the empirical null distribution in BACON. Enrichment and pathway analyses were performed on genes annotated to cytosine-phosphate-guanine (CpG) sites using the gometh function in missMethyl. We identified six significant DMRs (Sidak-corrected <i>P</i> values: 0.0006-0.0173), associated with paternal smoking, annotated to genes involved in innate and adaptive immunity, fatty acid synthesis, development and function of neuronal systems and cellular processes. DMP analysis identified 33 CpGs [false discovery rate (FDR)  < 0.05]. Following adjustment for genomic control (λ = 1.462), no DMPs remained epigenome-wide significant (FDR < 0.05). This hypothesis-generating study found that fathers' smoking was associated with differential methylation in their adolescent and adult offspring. Future studies are needed to explore the intriguing hypothesis that fathers' exposures might persistently modify their future offspring's epigenome.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"5 4","pages":"dvz023"},"PeriodicalIF":3.8,"publicationDate":"2019-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvz023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37450074","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":"Mothers' and fathers' cognitive and affective responses to epigenetics concepts.","authors":"Brittany M Hollister,&nbsp;Haley E Yaremych,&nbsp;Megan R Goldring,&nbsp;Susan Persky","doi":"10.1093/eep/dvz021","DOIUrl":"https://doi.org/10.1093/eep/dvz021","url":null,"abstract":"<p><p>Advances in our understanding of epigenetics present new opportunities to improve children's health through the counseling of parents about epigenetics concepts. However, it is important to first evaluate how parents respond to this type of information and determine the consequences of educating parents about epigenetics. We have taken an initial step toward this goal by assessing parental responses to an epigenetics learning module. Parents (<i>n</i> = 190, 126 mothers) responded to pre- and post-module survey questions. Prior to the module, parents reported that mothers' lifestyles prior to conception were more important for children's health than fathers' lifestyles prior to conception (<i>t</i> = 4.49, df = 316.5, <i>P</i> < 0.0001). However, after the module, there was no difference between ratings of the importance of mothers' and fathers' preconception lifestyles (<i>t</i> = 1.18, df = 319.8, <i>P</i> = NS). Furthermore, after viewing the module, parents increased their ratings of the importance of both mothers' (<i>t</i> = -5.65, df = 294.8, <i>P</i> < 0.0001) and father's (<i>t</i> = -9.01, df = 287.2, <i>P</i> < 0.0001) preconception lifestyles for child health. After viewing the module, most parents reported feelings of guilt and negativity regarding epigenetics (78 and 55%, respectively). When compared with lean parents, parents with overweight more often reported feelings of guilt (<i>χ</i> ² =10.27, <i>P</i> = 0.001). This work represents an important first step in evaluating parental responses to epigenetics concepts.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"5 4","pages":"dvz021"},"PeriodicalIF":3.8,"publicationDate":"2019-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvz021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38648759","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":"Regional epigenetic variation in asexual snail populations among urban and rural lakes","authors":"Jennifer L. M. Thorson, Mark W. Smithson, Ingrid Sadler‐Riggleman, Daniel Beck, M. Dybdahl, M. Skinner","doi":"10.1093/eep/dvz020","DOIUrl":"https://doi.org/10.1093/eep/dvz020","url":null,"abstract":"Abstract Epigenetic variation has the potential to influence environmentally dependent development and contribute to phenotypic responses to local environments. Environmental epigenetic studies of sexual organisms confirm the capacity to respond through epigenetic variation. An epigenetic response could be even more important in a population when genetic variation is lacking. A previous study of an asexual snail, Potamopyrgus antipodarum, demonstrated that different populations derived from a single clonal lineage differed in both shell phenotype and methylation signature when comparing lake versus river populations. Here, we examine methylation variation among lakes that differ in environmental disturbance and pollution histories. Snails were collected from a more pristine rural Lake 1 (Lake Lytle), and two urban lakes, Lake 2 (Capitol Lake) and Lake 3 (Lake Washington) on the Northwest Pacific coast. DNA methylation was assessed for each sample population using methylated DNA immunoprecipitation, MeDIP, followed by next-generation sequencing. The differential DNA methylation regions (DMRs) identified among the different lake comparisons suggested a higher number of DMRs and variation between rural Lake 1 and one urban Lake 2, and between the two urban Lakes 2 and 3, but limited variation between the rural Lake 1 and urban Lake 3. DMR genomic characteristics and gene associations were investigated. The presence of site-specific differences between each of these lake populations suggest an epigenetic response to varied environmental factors. The results do not support an effect of geographic distance in these populations. The role of dispersal distance among lakes, population history, environmental pollution and stably inherited methylation versus environmentally triggered methylation in producing the observed epigenetic variation are discussed. Observations support the proposal that epigenetic alterations may associate with phenotypic variation and environmental factors and history of the different lakes.","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/dvz020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49282167","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":"The epigenetic legacy of illicit drugs: developmental exposures and late-life phenotypes","authors":"N. Wanner, Mathia Colwell, Christopher D. Faulk","doi":"10.1093/eep/dvz022","DOIUrl":"https://doi.org/10.1093/eep/dvz022","url":null,"abstract":"Abstract The effects of in utero exposure to illicit drugs on adult offspring are a significant and widespread but understudied global health concern, particularly in light of the growing opioid epidemic and emerging therapeutic uses for cannabis, ketamine, and MDMA. Epigenetic mechanisms including DNA methylation, histone modifications, and expression of non-coding RNAs provide a mechanistic link between the prenatal environment and health consequences years beyond the original exposure, and shifts in the epigenome present in early life or adolescence can lead to disease states only appearing during adulthood. The current review summarizes the literature assessing effects of perinatal illicit drug exposure on adult disease phenotypes as mediated by perturbations of the epigenome. Both behavioral and somatic phenotypes are included and studies reporting clinical data in adult offspring, epigenetic readouts in offspring of any age, or both phenotypic and epigenetic measures are prioritized. Studies of licit substances of abuse (i.e. alcohol, nicotine) are excluded with a focus on cannabis, psychostimulants, opioids, and psychedelics; current issues in the field and areas of interest for further investigation are also discussed.","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/dvz022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47731037","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":"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}