C. Dupras, S. Beck, M. Rothstein, A. Berner, Katie M. Saulnier, Miriam Pinkesz, A. Prince, Stamatina Liosi, Lingqiao Song, Y. Joly
{"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}
Ge Li, T. D. Petkova, Eleonora Laritsky, Noah J. Kessler, Maria S. Baker, Shaoyu Zhu, R. Waterland
{"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}
Laura Moody, Diego Hernández-Saavedra, Daniel G Kougias, Hong Chen, Janice M Juraska, Yuan-Xiang Pan
{"title":"Tissue-specific changes in <i>Srebf1</i> and <i>Srebf2</i> expression and DNA methylation with perinatal phthalate exposure.","authors":"Laura Moody, Diego Hernández-Saavedra, Daniel G Kougias, Hong Chen, Janice M Juraska, 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}
Stephanie E King, Margaux McBirney, Daniel Beck, Ingrid Sadler-Riggleman, Eric Nilsson, Michael K Skinner
{"title":"Sperm epimutation biomarkers of obesity and pathologies following DDT induced epigenetic transgenerational inheritance of disease.","authors":"Stephanie E King, Margaux McBirney, Daniel Beck, Ingrid Sadler-Riggleman, Eric Nilsson, Michael K Skinner","doi":"10.1093/eep/dvz008","DOIUrl":"https://doi.org/10.1093/eep/dvz008","url":null,"abstract":"<p><p>Dichlorodiphenyltrichloroethane (DDT) has previously been shown to promote the epigenetic transgenerational inheritance of adult onset disease in rats. The current study investigated the potential that sperm epimutation biomarkers can be used to identify ancestral induced transgenerational obesity and associated pathologies. Gestating F0 generational female rats were transiently exposed to DDT during fetal gonadal sex determination, and the incidence of adult-onset pathologies was assessed in the subsequent F1, F2, and F3 generations. In addition, sperm differential DNA methylation regions (DMRs) that were associated with specific pathologies in the transgenerational F3 generation males were investigated. There was an increase of testis disease and early-onset puberty in the F2 generation DDT lineage males. The F3 generation males and females had significant increases in the incidence of obesity and multiple disease. The F3 generation DDT males also had significant increases in testis disease, prostate disease, and late onset puberty. The F3 generation DDT females had increases in ovarian and kidney disease. Epigenetic alterations of the germline are required for the transgenerational inheritance of pathology. Therefore, the F3 generation sperm was collected to examine DMRs for the ancestrally exposed DDT male population. Unique sets of DMRs were associated with late onset puberty, prostate disease, kidney disease, testis disease, obesity, and multiple disease pathologies. Gene associations with the DMR were also identified. The epigenetic DMR signatures identified for these pathologies provide potential biomarkers for transgenerationally inherited disease susceptibility.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"5 2","pages":"dvz008"},"PeriodicalIF":3.8,"publicationDate":"2019-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvz008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37323265","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}
Wayo Matsushima, Kristiana Brink, Julia Schroeder, Eric A Miska, Katharina Gapp
{"title":"Mature sperm small-RNA profile in the sparrow: implications for transgenerational effects of age on fitness.","authors":"Wayo Matsushima, Kristiana Brink, Julia Schroeder, Eric A Miska, Katharina Gapp","doi":"10.1093/eep/dvz007","DOIUrl":"10.1093/eep/dvz007","url":null,"abstract":"<p><p>Mammalian sperm RNA has recently received a lot of interest due to its involvement in epigenetic germline inheritance. Studies of epigenetic germline inheritance have shown that environmental exposures can induce effects in the offspring without altering the DNA sequence of germ cells. Most mechanistic studies were conducted in laboratory rodents and <i>C.elegans</i> while observational studies confirm the phenotypic phenomenon in wild populations of humans and other species including birds. Prominently, paternal age in house sparrows affects offspring fitness, yet the mechanism is unknown. This study provides a first reference of house sparrow sperm small RNA as an attempt to uncover their role in the transmission of the effects of paternal age on the offspring. In this small-scale pilot, we found no statistically significant differences between miRNA and tRNA fragments in aged and prime sparrow sperm. These results indicate a role of other epigenetic information carriers, such as distinct RNA classes, RNA modifications, DNA methylation and retained histones, and a clear necessity of future studies in wild populations.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"5 2","pages":"dvz007"},"PeriodicalIF":4.8,"publicationDate":"2019-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37286782","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":"Environmental Epigenetics Update and Boards.","authors":"Michael K Skinner","doi":"10.1093/eep/dvz006","DOIUrl":"https://doi.org/10.1093/eep/dvz006","url":null,"abstract":"Environmental Epigenetics, an Oxford University Press publication, just initiated its fifth year of operations with this Volume 5 Issue 1. We are a completely Open Access journal listed in PMC and PubMed, along with numerous other access sites. Environmental Epigenetics initiated its review to obtain an impact factor this year. Two special issues are planned this year in Epigenetics, Environment and Reproduction and in Epigenetic Transgenerational Inheritance, both associated with corresponding scientific meetings around the world. The amount and diversity of our published studies is increasing as the field of environmental epigenetics grows and expands. We are looking forward to another productive year and encourage you to consider submissions to Environmental Epigenetics. The heart of the journal has always been the quality and breadth of the Environmental Epigenetics Editorial Boards. This Editorial is designed to extend a profound thanks to the Editorial Boards. From the beginning the Editorial Board, Consulting Editorial Board, and Editorial Review Board have provided advice and insights into the development and operations of the journal and its review process. I personally want to thank all those Editors that have acted as managing editors and reviewers. Without the dedication, experience and hard work of the Editorial Boards the journal would not exist. The current members of each of the Boards are listed below. You will see an outstanding group of dedicated and hardworking individuals that truly are the backbone of Environmental Epigenetics.","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"5 1","pages":"dvz006"},"PeriodicalIF":3.8,"publicationDate":"2019-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvz006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37258533","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}
J Keiko McCreary, Zachary T Erickson, Eric Paxman, Douglas Kiss, Tony Montina, David M Olson, Gerlinde A S Metz
{"title":"The rat cumulative allostatic load measure (rCALM): a new translational assessment of the burden of stress.","authors":"J Keiko McCreary, Zachary T Erickson, Eric Paxman, Douglas Kiss, Tony Montina, David M Olson, Gerlinde A S Metz","doi":"10.1093/eep/dvz005","DOIUrl":"https://doi.org/10.1093/eep/dvz005","url":null,"abstract":"<p><p>Determinants of lifetime health are complex and emphasize the need for robust predictors of disease risk. Allostatic load (AL) has become a clinical framework to estimate the cumulative biological burden associated with chronic stress. To assist knowledge translation in the developmental origins of health and disease field, clinically valid methods for reliable AL assessment in experimental models are urgently needed. Here, we introduce the rat cumulative allostatic load measure (rCALM), as a new preclinical knowledge translation tool to assess the burden of chronic stress. First, we identified an array of stress-associated physiological markers that are particularly sensitive to hypothalamic-pituitary-adrenal axis dysregulation by ancestral prenatal stress. Second, we determined which of these markers are susceptible to an intervention by environmental enrichment (EE) to mitigate AL. The markers most responsive to stress and EE therapy were assembled to become operationalized in the rCALM. Third, the new rCALM was validated for the ability to indicate future disease risks. The results show that the rCALM estimates the burden of chronic stress and serves as a proxy to estimate stress resilience and vulnerability to disease. Using the rCALM we showed that enrichment therapy can offset the adverse health outcomes linked to a high AL. Thus, the rCALM provides a model for the development of new test strategies that facilitate knowledge translation in preclinical animal models.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"5 1","pages":"dvz005"},"PeriodicalIF":3.8,"publicationDate":"2019-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvz005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37220890","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}
Kezia A Addo, C. Bulka, Radhika Dhingra, Hudson P. Santos, L. Smeester, T. O’Shea, Rebecca C. Fry
{"title":"Acetaminophen use during pregnancy and DNA methylation in the placenta of the extremely low gestational age newborn (ELGAN) cohort","authors":"Kezia A Addo, C. Bulka, Radhika Dhingra, Hudson P. Santos, L. Smeester, T. O’Shea, Rebecca C. Fry","doi":"10.1093/eep/dvz010","DOIUrl":"https://doi.org/10.1093/eep/dvz010","url":null,"abstract":"Abstract Acetaminophen is considered the safest antipyretic and analgesic medication for pregnant women. However, studies have reported that acetaminophen has endocrine disrupting properties and prenatal exposure has been associated with early life epigenetic changes and later life health outcomes. As the placenta is the central mediator of maternal and fetal interactions, exposure to acetaminophen during pregnancy could manifest as perturbations in the placenta epigenome. Here, we evaluated epigenome-wide cytosine-guanine dinucleotide (CpG) methylation in placental tissue in relation to maternal acetaminophen use during pregnancy in a cohort of 286 newborns born prior to 28 weeks gestation. According to maternal self-report, more than half (166 of 286) of the newborns were exposed to acetaminophen in utero. After adjustment for potential confounders, a total of 42 CpGs were identified to be differentially methylated at a false discovery rate < 0.05, with most displaying increased methylation as it relates to acetaminophen exposure. A notable gene that was significantly associated with acetaminophen is the prostaglandin receptor (PTGDR) which plays an essential role in mediating placental blood flow and fetal growth. Moreover, for 6 of the 42 CpGs, associations of acetaminophen use with methylation were significantly different between male and female placentas; 3 CpG sites were associated with acetaminophen use in the male placenta and 3 different sites were associated with acetaminophen use in the female placenta (Pinteraction < 0.2). These findings highlight a relationship between maternal acetaminophen use during pregnancy and the placental epigenome and suggest that the responses for some CpG sites are sex dependent.","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvz010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45146576","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}
Gwen Tindula, Douglas Lee, Karen Huen, Asa Bradman, Brenda Eskenazi, Nina Holland
{"title":"Pregnancy lipidomic profiles and DNA methylation in newborns from the CHAMACOS cohort.","authors":"Gwen Tindula, Douglas Lee, Karen Huen, Asa Bradman, Brenda Eskenazi, Nina Holland","doi":"10.1093/eep/dvz004","DOIUrl":"https://doi.org/10.1093/eep/dvz004","url":null,"abstract":"<p><p>Lipids play a role in many biological functions and the newly emerging field of lipidomics aims to characterize the varying classes of lipid molecules present in biological specimens. Animal models have shown associations between maternal dietary supplementation with fatty acids during pregnancy and epigenetic changes in their offspring, demonstrating a mechanism through which prenatal environment can affect outcomes in children; however, data on maternal lipid metabolite levels during pregnancy and newborn DNA methylation in humans are sparse. In this study, we assessed the relationship of maternal lipid metabolites measured in the blood from pregnant women with newborn DNA methylation profiles in the Center for the Health Assessment of Mothers and Children of Salinas cohort. Targeted metabolomics was performed by selected reaction monitoring liquid chromatography and triple quadrupole mass spectrometry to measure 92 metabolites in plasma samples of pregnant women at ∼26 weeks gestation. DNA methylation was assessed using the Infinium HumanMethylation 450K BeadChip adjusting for cord blood cell composition. We uncovered numerous false discovery rate significant associations between maternal metabolite levels, particularly phospholipid and lysolipid metabolites, and newborn methylation. The majority of the observed relationships were negative, suggesting that higher lipid metabolites during pregnancy are associated with lower methylation levels at genes related to fetal development. These results further elucidate the complex relationship between early life exposures, maternal lipid metabolites, and infant epigenetic status.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"5 1","pages":"dvz004"},"PeriodicalIF":3.8,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvz004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37130150","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}