{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T21:57:25Z","timestamp":1788818245046,"version":"build-2803163510"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T00:00:00Z","timestamp":1629676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["31003A-135715"],"award-info":[{"award-number":["31003A-135715"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003006","name":"ETH","doi-asserted-by":"publisher","award":["ETH-10 15-2"],"award-info":[{"award-number":["ETH-10 15-2"]}],"id":[{"id":"10.13039\/501100003006","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003006","name":"ETH","doi-asserted-by":"publisher","award":["ETH-17 13-2"],"award-info":[{"award-number":["ETH-17 13-2"]}],"id":[{"id":"10.13039\/501100003006","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Swiss Federal Institute of Technology"},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["31003A-135715"],"award-info":[{"award-number":["31003A-135715"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sperm RNA can be modified by environmental factors and has been implicated in communicating signals about changes in a father's environment to the offspring. The small RNA composition of sperm could be changed during its final stage of maturation in the epididymis by extracellular vesicles (EVs) released by epididymal cells. We studied the effect of exposure to stress in early postnatal life on the transcriptome of epididymal EVs using a mouse model of transgenerational transmission. We found that the small RNA signature of epididymal EVs, particularly miRNAs, is altered in adult males exposed to postnatal stress. In some cases, these miRNA changes correlate with differences in the expression of their target genes in sperm and zygotes generated from that sperm. These results suggest that stressful experiences in early life can have persistent biological effects on the male reproductive tract that may in part be responsible for the transmission of the effects of exposure to the offspring.<\/jats:p>","DOI":"10.1093\/biolre\/ioab156","type":"journal-article","created":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T20:20:28Z","timestamp":1629750028000},"page":"593-602","source":"Crossref","is-referenced-by-count":26,"title":["Early life stress affects the miRNA cargo of epididymal extracellular vesicles in mouse"],"prefix":"10.1093","volume":"105","author":[{"given":"Anar","family":"Alshanbayeva","sequence":"first","affiliation":[{"name":"Laboratory of Neuroepigenetics, Brain Research Institute at the Medical Faculty of the University of Zurich, Zurich, Switzerland"},{"name":"Institute for Neuroscience of the Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland"},{"name":"Zurich Neuroscience Center, ETH and University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak K","family":"Tanwar","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroepigenetics, Brain Research Institute at the Medical Faculty of the University of Zurich, Zurich, Switzerland"},{"name":"Institute for Neuroscience of the Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland"},{"name":"Zurich Neuroscience Center, ETH and University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Roszkowski","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroepigenetics, Brain Research Institute at the Medical Faculty of the University of Zurich, Zurich, Switzerland"},{"name":"Institute for Neuroscience of the Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland"},{"name":"Zurich Neuroscience Center, ETH and University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Manuella","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroepigenetics, Brain Research Institute at the Medical Faculty of the University of Zurich, Zurich, Switzerland"},{"name":"Institute for Neuroscience of the Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland"},{"name":"Zurich Neuroscience Center, ETH and University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle M","family":"Mansuy","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroepigenetics, Brain Research Institute at the Medical Faculty of the University of Zurich, Zurich, Switzerland"},{"name":"Institute for Neuroscience of the Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland"},{"name":"Zurich Neuroscience Center, ETH and University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,8,23]]},"reference":[{"key":"2021091612445447600_ref1","article-title":"Roles of male reproductive tract extracellular vesicles in reproduction","volume":"85","author":"Tamessar","year":"2020","journal-title":"Am J Reprod Immunol"},{"key":"2021091612445447600_ref2","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1126\/science.aad6780","article-title":"Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals","volume":"351","author":"Sharma","year":"2016","journal-title":"Science"},{"key":"2021091612445447600_ref3","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1095\/biolreprod.115.132209","article-title":"The microRNA signature of mouse spermatozoa is substantially modified during epididymal maturation","volume":"93","author":"Nixon","year":"2015","journal-title":"Biol Reprod"},{"key":"2021091612445447600_ref4","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1095\/biolreprod.105.049304","article-title":"Lipid remodeling of murine epididymosomes and spermatozoa during epididymal maturation","volume":"74","author":"Rejraji","year":"2006","journal-title":"Biol Reprod"},{"key":"2021091612445447600_ref5","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0140650","article-title":"Sperm proteome maturation in the mouse epididymis","volume":"10","author":"Skerget","year":"2015","journal-title":"PLoS One"},{"key":"2021091612445447600_ref6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13072-020-00340-0","article-title":"A comprehensive overview of bull sperm-borne small non-coding RNAs and their diversity across breeds","volume":"13","author":"Sellem","year":"2020","journal-title":"Epigenetics Chromatin"},{"key":"2021091612445447600_ref7","doi-asserted-by":"crossref","first-page":"31794","DOI":"10.1038\/srep31794","article-title":"Characterisation of mouse epididymosomes reveals a complex profile of microRNAs and a potential mechanism for modification of the sperm epigenome","volume":"6","author":"Reilly","year":"2016","journal-title":"Sci Rep"},{"key":"2021091612445447600_ref8","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0065364","article-title":"CD9-positive microvesicles mediate the transfer of molecules to bovine spermatozoa during epididymal maturation","volume":"8","author":"Caballero","year":"2013","journal-title":"PLoS One"},{"key":"2021091612445447600_ref9","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1093\/humrep\/den181","article-title":"Protein composition of human epididymosomes collected during surgical vasectomy reversal: a proteomic and genomic approach","volume":"23","author":"Thimon","year":"2008","journal-title":"Hum Reprod"},{"key":"2021091612445447600_ref10","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s12915-019-0653-5","article-title":"Mechanisms of tethering and cargo transfer during epididymosome-sperm interactions","volume":"17","author":"Zhou","year":"2019","journal-title":"BMC Biol"},{"key":"2021091612445447600_ref11","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1002\/mrd.1080300305","article-title":"Liposome-mediated DNA uptake by sperm cells","volume":"30","author":"Bachiller","year":"1991","journal-title":"Mol Reprod Dev"},{"key":"2021091612445447600_ref12","doi-asserted-by":"crossref","first-page":"3101","DOI":"10.1093\/humrep\/dei169","article-title":"Decline in fertility of mouse sperm with abnormal chromatin during epididymal passage as revealed by ICSI","volume":"20","author":"Suganuma","year":"2005","journal-title":"Hum Reprod"},{"key":"2021091612445447600_ref13","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.devcel.2018.06.024","article-title":"Small RNAs gained during epididymal transit of sperm are essential for embryonic development in mice","volume":"46","author":"Conine","year":"2018","journal-title":"Dev Cell"},{"key":"2021091612445447600_ref14","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1038\/s41467-020-15305-w","article-title":"Reproductive tract extracellular vesicles are sufficient to transmit intergenerational stress and program neurodevelopment","volume":"11","author":"Chan","year":"2020","journal-title":"Nat Commun"},{"key":"2021091612445447600_ref15","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/nn.3695","article-title":"Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice","volume":"17","author":"Gapp","year":"2014","journal-title":"Nat Neurosci"},{"key":"2021091612445447600_ref16","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.biopsych.2010.05.036","article-title":"Epigenetic transmission of the impact of early stress across generations","volume":"68","author":"Franklin","year":"2010","journal-title":"Biol Psychiatry"},{"key":"2021091612445447600_ref17","first-page":"171","article-title":"Structural analysis of exosomes using different types of electron microscopy","volume":"47","author":"Choi","year":"2017","journal-title":"Am Demogr"},{"key":"2021091612445447600_ref18","article-title":"Sperm microRNAs confer depression susceptibility to offspring","volume":"7","author":"Wang","year":"2021","journal-title":"Sci Adv"},{"key":"2021091612445447600_ref19","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/s41556-018-0087-2","article-title":"Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs","volume":"20","author":"Zhang","year":"2018","journal-title":"Nat Cell Biol"},{"key":"2021091612445447600_ref20","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2020104579","article-title":"Involvement of circulating factors in the transmission of paternal experiences through the germline","volume":"39","author":"Steenwyk","year":"2020","journal-title":"EMBO J"},{"key":"2021091612445447600_ref21","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1093\/molehr\/gah197","article-title":"Macrophage migration inhibitory factor in the human epididymis and semen","volume":"11","author":"Frenette","year":"2005","journal-title":"Mol Hum Reprod"},{"key":"2021091612445447600_ref22","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1093\/humrep\/det088","article-title":"microRNA signature is altered in both human epididymis and seminal microvesicles following vasectomy","volume":"28","author":"Belleann\u00e9e","year":"2013","journal-title":"Hum Reprod"},{"key":"2021091612445447600_ref23","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1038\/s41380-018-0271-6","article-title":"Alterations in sperm long RNA contribute to the epigenetic inheritance of the effects of postnatal trauma","volume":"25","author":"Gapp","year":"2020","journal-title":"Mol Psychiatry"},{"key":"2021091612445447600_ref24","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/978-1-4939-6563-2_2","article-title":"Functional analysis of miRNAs using the DIANA tools online suite","volume":"1517","author":"Vlachos","year":"2017","journal-title":"Methods Mol Biol"},{"key":"2021091612445447600_ref25","doi-asserted-by":"crossref","first-page":"726","DOI":"10.4103\/1008-682X.155255","article-title":"Epididymosomes: a heterogeneous population of microvesicles with multiple functions in sperm maturation and storage","volume":"17","author":"Sullivan","year":"2015","journal-title":"Asian J Androl"},{"key":"2021091612445447600_ref26","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1095\/biolreprod.113.110486","article-title":"Epididymosomes convey different repertoires of microRNAs throughout the bovine epididymis","volume":"89","author":"Belleann\u00e9e","year":"2013","journal-title":"Biol Reprod"},{"key":"2021091612445447600_ref27","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/brv.12459","article-title":"Roles of microRNAs in mammalian reproduction: from the commitment of germ cells to peri-implantation embryos","volume":"94","author":"Reza","year":"2019","journal-title":"Biol Rev Camb Philos Soc"},{"key":"2021091612445447600_ref28","doi-asserted-by":"crossref","first-page":"263","DOI":"10.3389\/fimmu.2017.00263","article-title":"miR-31 links lipid metabolism and cell apoptosis in bacteria-challenged Apostichopus japonicus via targeting CTRP9","volume":"8","author":"Shao","year":"2017","journal-title":"Front Immunol"},{"key":"2021091612445447600_ref29","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4615-0679-9","volume-title":"The Epididymis: From Molecules to Clinical Practice","author":"Robaire","year":"2002"},{"key":"2021091612445447600_ref30","doi-asserted-by":"crossref","first-page":"592","DOI":"10.2164\/jandrol.111.014266","article-title":"Androgen action in the epididymis","volume":"32","author":"Robaire","year":"2011","journal-title":"J Androl"},{"key":"2021091612445447600_ref31","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1095\/biolreprod63.2.368","article-title":"Effects of androgen on androgen receptor expression in rat testicular and epididymal cells: a quantitative immunohistochemical study","volume":"63","author":"Zhu","year":"2000","journal-title":"Biol Reprod"},{"key":"2021091612445447600_ref32","first-page":"43","article-title":"Hormonal status of male reproductive system: Androgens and estrogens in the testis and epididymis. In vivo and in vitro approaches","volume":"6","author":"Bili\u0144ska","year":"2006","journal-title":"Reprod Biol"},{"key":"2021091612445447600_ref33","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.nano.2011.04.003","article-title":"Sizing and phenotyping of cellular vesicles using nanoparticle tracking analysis","volume":"7","author":"Dragovic","year":"2011","journal-title":"Nanomedicine"},{"key":"2021091612445447600_ref34","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.cels.2019.03.004","article-title":"exceRpt: a comprehensive analytic platform for extracellular RNA profiling","volume":"8","author":"Rozowsky","year":"2019","journal-title":"Cell Syst"},{"key":"2021091612445447600_ref35","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"2021091612445447600_ref36","first-page":"42","article-title":"Svaseq: removing batch effects and other unwanted noise from sequencing data","author":"Leek","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"2021091612445447600_ref37","doi-asserted-by":"crossref","first-page":"R25","DOI":"10.1186\/gb-2010-11-3-r25","article-title":"A scaling normalization method for differential expression analysis of RNA-seq data","volume":"11","author":"Robinson","year":"2010","journal-title":"Genome Biol"},{"key":"2021091612445447600_ref38","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":"2021091612445447600_ref39","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.05005","article-title":"Predicting effective microRNA target sites in mammalian mRNAs","volume":"4","author":"Agarwal","year":"2015","journal-title":"Elife"},{"key":"2021091612445447600_ref40","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-24277-4","volume-title":"ggplot2: Elegant Graphics for Data Analysis","author":"Wickham","year":"2016"},{"key":"2021091612445447600_ref41","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex heatmaps reveal patterns and correlations in multidimensional genomic data","volume":"32","author":"Gu","year":"2016","journal-title":"Bioinformatics"}],"container-title":["Biology of Reproduction"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/biolreprod\/advance-article-pdf\/doi\/10.1093\/biolre\/ioab156\/40135552\/ioab156.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/biolreprod\/article-pdf\/105\/3\/593\/40394074\/ioab156.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/biolreprod\/article-pdf\/105\/3\/593\/40394074\/ioab156.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T14:29:38Z","timestamp":1699367378000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biolreprod\/article\/105\/3\/593\/6356601"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,23]]},"references-count":41,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,8,23]]},"published-print":{"date-parts":[[2021,9,14]]}},"URL":"https:\/\/doi.org\/10.1093\/biolre\/ioab156","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.04.29.441964","asserted-by":"object"}]},"ISSN":["0006-3363","1529-7268"],"issn-type":[{"value":"0006-3363","type":"print"},{"value":"1529-7268","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,9]]},"published":{"date-parts":[[2021,8,23]]}}}