{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T13:38:39Z","timestamp":1785245919123,"version":"3.55.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T00:00:00Z","timestamp":1608595200000},"content-version":"vor","delay-in-days":356,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000925","name":"John Templeton Foundation","doi-asserted-by":"publisher","award":["50183"],"award-info":[{"award-number":["50183"]}],"id":[{"id":"10.13039\/100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000925","name":"John Templeton Foundation","doi-asserted-by":"publisher","award":["61174"],"award-info":[{"award-number":["61174"]}],"id":[{"id":"10.13039\/100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats: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.<\/jats:p>","DOI":"10.1093\/eep\/dvaa020","type":"journal-article","created":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T18:30:58Z","timestamp":1608661858000},"source":"Crossref","is-referenced-by-count":15,"title":["Epigenome-wide association study (EWAS) for potential transgenerational disease epigenetic biomarkers in sperm following ancestral exposure to the pesticide methoxychlor"],"prefix":"10.1093","volume":"6","author":[{"given":"Eric E","family":"Nilsson","sequence":"first","affiliation":[{"name":"Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164-4236, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L M","family":"Thorson","sequence":"additional","affiliation":[{"name":"Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164-4236, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Millissia","family":"Ben Maamar","sequence":"additional","affiliation":[{"name":"Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164-4236, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Beck","sequence":"additional","affiliation":[{"name":"Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164-4236, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8224-2078","authenticated-orcid":false,"given":"Michael K","family":"Skinner","sequence":"additional","affiliation":[{"name":"Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164-4236, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,22]]},"reference":[{"key":"2020122308392880900_dvaa020-B1","doi-asserted-by":"crossref","DOI":"10.1093\/eep\/dvy016","article-title":"Environmentally induced epigenetic transgenerational inheritance of disease","volume":"4","author":"Nilsson","year":"2018","journal-title":"Environ Epigenet"},{"key":"2020122308392880900_dvaa020-B2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.pbiomolbio.2015.02.008","article-title":"Epigenetic inheritance and evolution: a paternal perspective on dietary influences","volume":"118","author":"Soubry","year":"2015","journal-title":"Prog Biophys Mol Biol"},{"key":"2020122308392880900_dvaa020-B3","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13072-017-0145-1","article-title":"Non-genomic transmission of longevity between generations: potential mechanisms and evidence across species","volume":"10","author":"Vaiserman","year":"2017","journal-title":"Epigenetics Chromatin"},{"key":"2020122308392880900_dvaa020-B4","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.3390\/cells8121559","article-title":"Transgenerational inheritance of environmentally induced epigenetic alterations during mammalian development","volume":"8","author":"Legoff","year":"2019","journal-title":"Cells"},{"key":"2020122308392880900_dvaa020-B5","doi-asserted-by":"crossref","first-page":"S137","DOI":"10.1016\/j.jpeds.2006.06.064","article-title":"Epigenetic mechanisms and gastrointestinal development","volume":"149","author":"Waterland","year":"2006","journal-title":"J Pediatr"},{"key":"2020122308392880900_dvaa020-B6","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2217\/epi.09.11","article-title":"Environmental signals and transgenerational epigenetics","volume":"1","author":"Skinner","year":"2009","journal-title":"Epigenomics"},{"key":"2020122308392880900_dvaa020-B7","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.reprotox.2007.09.001","article-title":"What is an epigenetic transgenerational phenotype? F3 or F2","volume":"25","author":"Skinner","year":"2008","journal-title":"Reprod Toxicol"},{"key":"2020122308392880900_dvaa020-B8","doi-asserted-by":"crossref","first-page":"838","DOI":"10.4161\/epi.6.7.16537","article-title":"Environmental epigenetic transgenerational inheritance and somatic epigenetic mitotic stability","volume":"6","author":"Skinner","year":"2011","journal-title":"Epigenetics"},{"key":"2020122308392880900_dvaa020-B9","first-page":"259","article-title":"Methoxychlor","volume":"20","year":"1979","journal-title":"IARC Monogr Eval Carcinog Risk Chem Hum"},{"key":"2020122308392880900_dvaa020-B10","doi-asserted-by":"crossref","first-page":"367","DOI":"10.3109\/10408449709089899","article-title":"Methoxychlor as a model for environmental estrogens","volume":"27","author":"Cummings","year":"1997","journal-title":"Crit Rev Toxicol"},{"key":"2020122308392880900_dvaa020-B11","author":"EPA","year":"2020"},{"key":"2020122308392880900_dvaa020-B12","first-page":"1534","article-title":"Pesticide residue levels in foods in the United States from July 1, 1969, to June 30, 1976: summary","volume":"66","author":"Duggan","year":"1983","journal-title":"J Assoc Off Anal Chem"},{"key":"2020122308392880900_dvaa020-B13","doi-asserted-by":"crossref","first-page":"e102091","DOI":"10.1371\/journal.pone.0102091","article-title":"Pesticide methoxychlor promotes the epigenetic transgenerational inheritance of adult onset disease through the female germline","volume":"9","author":"Manikkam","year":"2014","journal-title":"PLoS One"},{"key":"2020122308392880900_dvaa020-B14","doi-asserted-by":"crossref","first-page":"e31901","DOI":"10.1371\/journal.pone.0031901","article-title":"Transgenerational actions of environmental compounds on reproductive disease and identification of epigenetic biomarkers of ancestral exposures","volume":"7","author":"Manikkam","year":"2012","journal-title":"PLoS One"},{"key":"2020122308392880900_dvaa020-B15","doi-asserted-by":"crossref","first-page":"e0184306","DOI":"10.1371\/journal.pone.0184306","article-title":"Atrazine induced epigenetic transgenerational inheritance of disease, lean phenotype and sperm epimutation pathology biomarkers","volume":"12","author":"McBirney","year":"2017","journal-title":"PLoS One"},{"key":"2020122308392880900_dvaa020-B16","doi-asserted-by":"crossref","first-page":"e0202662","DOI":"10.1371\/journal.pone.0202662","article-title":"Vinclozolin induced epigenetic transgenerational inheritance of pathologies and sperm epimutation biomarkers for specific diseases","volume":"13","author":"Nilsson","year":"2018","journal-title":"PLoS One"},{"key":"2020122308392880900_dvaa020-B17","doi-asserted-by":"crossref","first-page":"dvz008","DOI":"10.1093\/eep\/dvz008","article-title":"Sperm epimutation biomarkers of obesity and pathologies following DDT induced epigenetic transgenerational inheritance of disease","volume":"5","author":"King","year":"2019","journal-title":"Environ Epigenet"},{"key":"2020122308392880900_dvaa020-B18","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0892-0362(01)00191-X","article-title":"Ethological methods to study the effects of maternal exposure to estrogenic endocrine disrupters: a study with methoxychlor","volume":"24","author":"Palanza","year":"2002","journal-title":"Neurotoxicol Teratol"},{"key":"2020122308392880900_dvaa020-B19","year":"2002"},{"key":"2020122308392880900_dvaa020-B20","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1186\/1471-2164-15-692","article-title":"Role of CpG Deserts in the Epigenetic Transgenerational Inheritance of Differential DNA Methylation Regions","volume":"15","author":"Skinner","year":"2014","journal-title":"BMC Genomics"},{"key":"2020122308392880900_dvaa020-B21","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ydbio.2019.10.030","article-title":"Epigenetic transgenerational inheritance of parent-of-origin allelic transmission of outcross pathology and sperm epimutations","volume":"458","author":"Ben Maamar","year":"2020","journal-title":"Dev Biol"},{"key":"2020122308392880900_dvaa020-B22","doi-asserted-by":"crossref","first-page":"63","DOI":"10.14740\/wjon1191","article-title":"Epidemiology of prostate cancer","volume":"10","author":"Rawla","year":"2019","journal-title":"World J Oncol"},{"key":"2020122308392880900_dvaa020-B23","first-page":"1","article-title":"Prevalence of obesity among adults and youth: United States, 2015-2016","volume":"288","author":"Hales","year":"2017","journal-title":"NCHS Data Brief"},{"key":"2020122308392880900_dvaa020-B24","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1002\/gepi.10237","article-title":"Analysis of multilocus models of association","volume":"25","author":"Devlin","year":"2003","journal-title":"Genet Epidemiol"},{"key":"2020122308392880900_dvaa020-B25","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1093\/bioinformatics\/btn120","article-title":"A note on the false discovery rate and inconsistent comparisons between experiments","volume":"24","author":"Higdon","year":"2008","journal-title":"Bioinformatics"},{"key":"2020122308392880900_dvaa020-B26","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1093\/bioinformatics\/btl548","article-title":"Estimating p-values in small microarray experiments","volume":"23","author":"Yang","year":"2007","journal-title":"Bioinformatics"},{"key":"2020122308392880900_dvaa020-B27","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1055\/s-0038-1633989","article-title":"Multiplicity issues in microarray experiments","volume":"44","author":"Bretz","year":"2005","journal-title":"Methods Inf Med"},{"key":"2020122308392880900_dvaa020-B28","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/978-1-60761-580-4_5","article-title":"Sample size and power calculation for molecular biology studies","volume":"620","author":"Jung","year":"2010","journal-title":"Methods Mol Biol"},{"key":"2020122308392880900_dvaa020-B29","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/1471-2105-10-38","article-title":"On reliable discovery of molecular signatures","volume":"10","author":"Nilsson","year":"2009","journal-title":"BMC Bioinformatics"},{"key":"2020122308392880900_dvaa020-B30","doi-asserted-by":"crossref","first-page":"6372","DOI":"10.1038\/s41598-019-42860-0","article-title":"Assessment of glyphosate induced epigenetic transgenerational inheritance of pathologies and sperm epimutations: generational toxicology","volume":"9","author":"Kubsad","year":"2019","journal-title":"Sci Rep"},{"key":"2020122308392880900_dvaa020-B31","doi-asserted-by":"crossref","first-page":"dvy010","DOI":"10.1093\/eep\/dvy010","article-title":"Alterations in sperm DNA methylation, non-coding RNA expression, and histone retention mediate vinclozolin-induced epigenetic transgenerational inheritance of disease","volume":"4","author":"Ben Maamar","year":"2018","journal-title":"Environ Epigenet"},{"key":"2020122308392880900_dvaa020-B32","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: a flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"2020122308392880900_dvaa020-B33","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat Methods"},{"key":"2020122308392880900_dvaa020-B34","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2020122308392880900_dvaa020-B35","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1093\/bioinformatics\/btt650","article-title":"MEDIPS: genome-wide differential coverage analysis of sequencing data derived from DNA enrichment experiments","volume":"30","author":"Lienhard","year":"2014","journal-title":"Bioinformatics"},{"key":"2020122308392880900_dvaa020-B36","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"2020122308392880900_dvaa020-B37","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1038\/nprot.2009.97","article-title":"Mapping identifiers for the integration of genomic datasets with the R\/Bioconductor package biomaRt","volume":"4","author":"Durinck","year":"2009","journal-title":"Nat Protoc"},{"key":"2020122308392880900_dvaa020-B38","doi-asserted-by":"crossref","first-page":"D662","DOI":"10.1093\/nar\/gku1010","article-title":"Ensembl 2015","volume":"43","author":"Cunningham","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2020122308392880900_dvaa020-B39","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"2020122308392880900_dvaa020-B40","doi-asserted-by":"crossref","first-page":"D199","DOI":"10.1093\/nar\/gkt1076","article-title":"Data, information, knowledge and principle: back to metabolism in KEGG","volume":"42","author":"Kanehisa","year":"2014","journal-title":"Nucl Acids Res"},{"key":"2020122308392880900_dvaa020-B41","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang da","year":"2009","journal-title":"Nat Protoc"},{"key":"2020122308392880900_dvaa020-B42","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1038\/nprot.2013.092","article-title":"Large-scale gene function analysis with the PANTHER classification system","volume":"8","author":"Mi","year":"2013","journal-title":"Nat Protoc"}],"container-title":["Environmental Epigenetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/eep\/article-pdf\/6\/1\/dvaa020\/35092201\/dvaa020.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/eep\/article-pdf\/6\/1\/dvaa020\/35092201\/dvaa020.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T14:18:29Z","timestamp":1608733109000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eep\/article\/doi\/10.1093\/eep\/dvaa020\/6042522"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,1]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1,1]]}},"URL":"https:\/\/doi.org\/10.1093\/eep\/dvaa020","relation":{},"ISSN":["2058-5888"],"issn-type":[{"value":"2058-5888","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020]]},"published":{"date-parts":[[2020,1,1]]},"article-number":"dvaa020"}}