{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T14:20:04Z","timestamp":1783952404750,"version":"3.55.0"},"reference-count":74,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012774","name":"Innovationsfonden","doi-asserted-by":"publisher","award":["7045-00013B"],"award-info":[{"award-number":["7045-00013B"]}],"id":[{"id":"10.13039\/100012774","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Pregnancy rates for<jats:italic>in vitro<\/jats:italic>produced (IVP) embryos are usually lower than for embryos produced<jats:italic>in vivo<\/jats:italic>after ovarian superovulation (MOET). This is potentially due to alterations in their trophectoderm (TE), the outermost layer in physical contact with the maternal endometrium. The main objective was to apply a multi-omics data integration approach to identify both temporally differentially expressed and differentially methylated genes (DEG and DMG), between IVP and MOET embryos, that could impact TE function. To start, four and five published transcriptomic and epigenomic datasets, respectively, were processed for data integration. Second, DEG from day 7 to days 13 and 16 and DMG from day 7 to day 17 were determined in the TE from IVP vs. MOET embryos. Third, genes that were both DE and DM were subjected to hierarchical clustering and functional enrichment analysis. Finally, findings were validated through a machine learning approach with two additional datasets from day 15 embryos. There were 1535 DEG and 6360 DMG, with 490 overlapped genes, whose expression profiles at days 13 and 16 resulted in three main clusters. Cluster 1 (188) and Cluster 2 (191) genes were down-regulated at day 13 or day 16, respectively, while Cluster 3 genes (111) were up-regulated at both days, in IVP embryos compared to MOET embryos. The top enriched terms were the KEGG pathway \"focal adhesion\" in Cluster 1 (FDR = 0.003), and the cellular component: \"extracellular exosome\" in Cluster 2 (FDR&lt;0.0001), also enriched in Cluster 1 (FDR = 0.04). According to the machine learning approach, genes in Cluster 1 showed a similar expression pattern between IVP and less developed (short) MOET conceptuses; and between MOET and DKK1-treated (advanced) IVP conceptuses. In conclusion, these results suggest that early conceptuses derived from IVP embryos exhibit epigenomic and transcriptomic changes that later affect its elongation and focal adhesion, impairing post-transfer survival.<\/jats:p>","DOI":"10.1371\/journal.pone.0252096","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T17:29:36Z","timestamp":1621877376000},"page":"e0252096","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Application of multi-omics data integration and machine learning approaches to identify epigenetic and transcriptomic differences between in vitro and in vivo produced bovine embryos"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0099-045X","authenticated-orcid":true,"given":"Maria B.","family":"Rabaglino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"O\u2019Doherty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7399-7142","authenticated-orcid":true,"given":"Jan","family":"Bojsen-M\u00f8ller Secher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Lonergan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poul","family":"Hyttel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trudee","family":"Fair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6294-382X","authenticated-orcid":true,"given":"Haja N.","family":"Kadarmideen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,5,24]]},"reference":[{"key":"pone.0252096.ref001","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1146\/annurev-animal-021419-084010","article-title":"Implications of Assisted Reproductive Technologies for Pregnancy Outcomes in Mammals","volume":"8","author":"PJ Hansen","year":"2020","journal-title":"Annu Rev Anim Biosci"},{"key":"pone.0252096.ref002","doi-asserted-by":"crossref","first-page":"10314","DOI":"10.3168\/jds.2017-13138","article-title":"A 100-Year Review: Reproductive technologies in dairy science","volume":"100","author":"SG Moore","year":"2017","journal-title":"J Dairy Sci"},{"key":"pone.0252096.ref003","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0301-6226(01)00291-3","article-title":"World statistics for artificial insemination in cattle","volume":"74","author":"M Thibier","year":"2002","journal-title":"Livestock Production Science"},{"key":"pone.0252096.ref004","first-page":"7","article-title":"Statistics of embryo production and transfer in domestic farm animals","volume":"38","author":"J Viana","year":"2019","journal-title":"Embryo Technology Newsletter. 2020"},{"key":"pone.0252096.ref005","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.theriogenology.2007.09.007","article-title":"In vitro-produced bovine embryos: dealing with the warts","volume":"69","author":"P Lonergan","year":"2008","journal-title":"Theriogenology"},{"key":"pone.0252096.ref006","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1093\/jas\/skz116","article-title":"BOARD INVITED REVIEW: Post-transfer consequences of in vitro-produced embryos in cattle","volume":"97","author":"AD Ealy","year":"2019","journal-title":"J Anim Sci"},{"key":"pone.0252096.ref007","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1093\/biolre\/ioz060","article-title":"Bovine endometrium responds differentially to age-matched short and long conceptuses","volume":"101","author":"JM S\u00e1nchez","year":"2019","journal-title":"Biol Reprod"},{"key":"pone.0252096.ref008","doi-asserted-by":"crossref","first-page":"F11","DOI":"10.1530\/REP-17-0257","article-title":"Chronicling the discovery of interferon tau","volume":"154","author":"FW Bazer","year":"2017","journal-title":"Reproduction"},{"key":"pone.0252096.ref009","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1071\/RD07089","article-title":"Effect of embryo source and recipient progesterone environment on embryo development in cattle","volume":"19","author":"P Lonergan","year":"2007","journal-title":"Reprod Fertil Dev"},{"key":"pone.0252096.ref010","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.domaniend.2015.03.004","article-title":"Maternal serum progesterone concentration and early conceptus development of bovine embryos produced in vivo or in vitro","volume":"52","author":"CV Barnwell","year":"2015","journal-title":"Domest Anim Endocrinol"},{"key":"pone.0252096.ref011","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1002\/mrd.90015","article-title":"Growth, development, and gene expression by in vivo- and in vitro-produced day 7 and 16 bovine embryos","volume":"63","author":"M Bertolini","year":"2002","journal-title":"Mol Reprod Dev"},{"key":"pone.0252096.ref012","doi-asserted-by":"crossref","first-page":"5687","DOI":"10.1073\/pnas.0812722106","article-title":"Endometrium as an early sensor of in vitro embryo manipulation technologies","volume":"106","author":"N Mansouri-Attia","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0252096.ref013","doi-asserted-by":"crossref","first-page":"5681","DOI":"10.1073\/pnas.0811841106","article-title":"The endometrium responds differently to cloned versus fertilized embryos","volume":"106","author":"S Bauersachs","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0252096.ref014","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1093\/biolre\/ioy199","article-title":"Interferon tau-dependent and independent effects of the bovine conceptus on the endometrial transcriptome","volume":"100","author":"DJ Mathew","year":"2019","journal-title":"Biol Reprod"},{"key":"pone.0252096.ref015","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/1471-2164-13-118","article-title":"RNA-Seq analysis uncovers transcriptomic variations between morphologically similar in vivo- and in vitro-derived bovine blastocysts","volume":"13","author":"AM Driver","year":"2012","journal-title":"BMC Genomics"},{"key":"pone.0252096.ref016","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1530\/rep.1.01015","article-title":"Suppressed expression of genes involved in transcription and translation in in vitro compared with in vivo cultured bovine embryos","volume":"131","author":"D Corcoran","year":"2006","journal-title":"Reproduction"},{"key":"pone.0252096.ref017","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1093\/humrep\/der110","article-title":"Effect of reproductive tract environment following controlled ovarian hyperstimulation treatment on embryo development and global transcriptome profile of blastocysts: implications for animal breeding and human assisted reproduction","volume":"26","author":"A Gad","year":"2011","journal-title":"Hum Reprod"},{"key":"pone.0252096.ref018","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s12864-016-2393-z","article-title":"Suboptimal culture conditions induce more deviations in gene expression in male than female bovine blastocysts","volume":"17","author":"S Heras","year":"2016","journal-title":"BMC Genomics"},{"key":"pone.0252096.ref019","doi-asserted-by":"crossref","first-page":"19768","DOI":"10.1073\/pnas.0805616105","article-title":"Genome-wide expression profiling reveals distinct clusters of transcriptional regulation during bovine preimplantation development in vivo","volume":"105","author":"WA Kues","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0252096.ref020","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/mrd.22165","article-title":"Transcriptome profile of bovine elongated conceptus obtained from SCNT and IVP pregnancies","volume":"80","author":"S Betsha","year":"2013","journal-title":"Mol Reprod Dev"},{"key":"pone.0252096.ref021","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1530\/REP-09-0152","article-title":"Progesterone and conceptus elongation in cattle: a direct effect on the embryo or an indirect effect via the endometrium?","volume":"138","author":"M Clemente","year":"2009","journal-title":"Reproduction"},{"key":"pone.0252096.ref022","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s00441-020-03257-y","article-title":"Genes associated with survival of female bovine blastocysts produced in vivo","volume":"382","author":"AM Zolini","year":"2020","journal-title":"Cell Tissue Res"},{"key":"pone.0252096.ref023","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1093\/biolre\/ioz190","article-title":"Molecular fingerprint of female bovine embryos produced in vitro with high competence to establish and maintain pregnancy","volume":"102","author":"AM Zolini","year":"2020","journal-title":"Biol Reprod"},{"key":"pone.0252096.ref024","doi-asserted-by":"crossref","first-page":"803","DOI":"10.4161\/epi.28711","article-title":"Epigenetic disorders and altered gene expression after use of Assisted Reproductive Technologies in domestic cattle","volume":"9","author":"R Urrego","year":"2014","journal-title":"Epigenetics"},{"issue":"5532","key":"pone.0252096.ref025","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1126\/science.293.5532.1103","article-title":"Genes, genetics, and epigenetics: a correspondence.[letter]","volume":"293","author":"C Wu","year":"2001","journal-title":"Science"},{"key":"pone.0252096.ref026","doi-asserted-by":"crossref","first-page":"a019133","DOI":"10.1101\/cshperspect.a019133","article-title":"DNA methylation in mammals","volume":"6","author":"E Li","year":"2014","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"pone.0252096.ref027","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/0092-8674(85)90312-5","article-title":"A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA","volume":"40","author":"A Bird","year":"1985","journal-title":"Cell"},{"key":"pone.0252096.ref028","doi-asserted-by":"crossref","first-page":"553","DOI":"10.2217\/epi.13.43","article-title":"DNA methylation and differentiation: silencing, upregulation and modulation of gene expression","volume":"5","author":"M Ehrlich","year":"2013","journal-title":"Epigenomics"},{"key":"pone.0252096.ref029","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/nrg3230","article-title":"Functions of DNA methylation: islands, start sites, gene bodies and beyond","volume":"13","author":"PA Jones","year":"2012","journal-title":"Nat Rev Genet"},{"key":"pone.0252096.ref030","doi-asserted-by":"crossref","first-page":"6711","DOI":"10.1002\/jcp.29566","article-title":"Putative promoters within gene bodies control exon expression via TET1-mediated H3K36 methylation","volume":"235","author":"L Ma","year":"2020","journal-title":"J Cell Physiol"},{"key":"pone.0252096.ref031","doi-asserted-by":"crossref","first-page":"e14524","DOI":"10.1371\/journal.pone.0014524","article-title":"DNA methylation of the first exon is tightly linked to transcriptional silencing","volume":"6","author":"F Brenet","year":"2011","journal-title":"PLoS One"},{"key":"pone.0252096.ref032","doi-asserted-by":"crossref","first-page":"250","DOI":"10.21451\/1984-3143-AR880","article-title":"DNA methylation dynamics during oocyte and embryo development and its association with environmental induced alterations","volume":"13","author":"T Fair","year":"2018","journal-title":"Animal Reproduction"},{"key":"pone.0252096.ref033","doi-asserted-by":"crossref","first-page":"e0140467","DOI":"10.1371\/journal.pone.0140467","article-title":"Genome-Wide DNA Methylation Patterns of Bovine Blastocysts Developed In Vivo from Embryos Completed Different Stages of Development In Vitro","volume":"10","author":"D Salilew-Wondim","year":"2015","journal-title":"PLoS One"},{"key":"pone.0252096.ref034","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.theriogenology.2019.12.020","article-title":"The age of the bull influences the transcriptome and epigenome of blastocysts produced by IVF","volume":"144","author":"C Wu","year":"2020","journal-title":"Theriogenology"},{"key":"pone.0252096.ref035","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1186\/s12864-018-4818-3","article-title":"Intragenic sequences in the trophectoderm harbour the greatest proportion of methylation errors in day 17 bovine conceptuses generated using assisted reproductive technologies","volume":"19","author":"AM O\u2019Doherty","year":"2018","journal-title":"BMC Genomics"},{"key":"pone.0252096.ref036","doi-asserted-by":"crossref","first-page":"D991","DOI":"10.1093\/nar\/gks1193","article-title":"NCBI GEO: archive for functional genomics data sets\u2014update","volume":"41","author":"T Barrett","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"pone.0252096.ref037","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene Expression Omnibus: NCBI gene expression and hybridization array data repository","volume":"30","author":"R Edgar","year":"2002","journal-title":"Nucleic Acids Res"},{"key":"pone.0252096.ref038","unstructured":"R Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria. 2020. http:\/\/www.r-project.org\/index.html."},{"key":"pone.0252096.ref039","unstructured":"Wu J, Irizarry R. gcrma: Background Adjustment Using Sequence Information. R package version 2.52.0. 2017"},{"key":"pone.0252096.ref040","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1093\/biostatistics\/kxj037","article-title":"Adjusting batch effects in microarray expression data using empirical Bayes methods","volume":"8","author":"WE Johnson","year":"2007","journal-title":"Biostatistics"},{"key":"pone.0252096.ref041","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1186\/1471-2164-15-451","article-title":"An integrated platform for bovine DNA methylome analysis suitable for small samples","volume":"15","author":"HA Shojaei Saadi","year":"2014","journal-title":"BMC Genomics"},{"key":"pone.0252096.ref042","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"ME Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"pone.0252096.ref043","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/1471-2105-14-165","article-title":"Separate-channel analysis of two-channel microarrays: recovering inter-spot information","volume":"14","author":"GK Smyth","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"pone.0252096.ref044","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1093\/bioinformatics\/bth078","article-title":"Open source clustering software","volume":"20","author":"MJ de Hoon","year":"2004","journal-title":"Bioinformatics"},{"key":"pone.0252096.ref045","doi-asserted-by":"crossref","first-page":"3246","DOI":"10.1093\/bioinformatics\/bth349","article-title":"Java Treeview\u2014extensible visualization of microarray data","volume":"20","author":"AJ Saldanha","year":"2004","journal-title":"Bioinformatics"},{"key":"pone.0252096.ref046","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":"W Huang da","year":"2009","journal-title":"Nat Protoc"},{"key":"pone.0252096.ref047","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1095\/biolreprod.111.092643","article-title":"RNA sequencing reveals novel gene clusters in bovine conceptuses associated with maternal recognition of pregnancy and implantation","volume":"85","author":"S Mamo","year":"2011","journal-title":"Biol Reprod"},{"key":"pone.0252096.ref048","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1002\/mrd.22640","article-title":"Differences in mRNA populations of short and long bovine conceptuses on Day 15 of gestation","volume":"83","author":"CV Barnwell","year":"2016","journal-title":"Mol Reprod Dev"},{"key":"pone.0252096.ref049","doi-asserted-by":"crossref","first-page":"11816","DOI":"10.1038\/s41598-019-48374-z","article-title":"Dickkopf-related protein 1 is a progestomedin acting on the bovine embryo during the morula-to-blastocyst transition to program trophoblast elongation","volume":"9","author":"P Tr\u00edbulo","year":"2019","journal-title":"Sci Rep"},{"key":"pone.0252096.ref050","doi-asserted-by":"crossref","DOI":"10.2202\/1544-6115.1008","article-title":"Parameter estimation for the calibration and variance stabilization of microarray data","volume":"2","author":"W Huber","year":"2003","journal-title":"Stat Appl Genet Mol Biol"},{"key":"pone.0252096.ref051","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"key":"pone.0252096.ref052","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1093\/bioinformatics\/btw650","article-title":"Improving cross-study prediction through addon batch effect adjustment or addon normalization","volume":"33","author":"R Hornung","year":"2017","journal-title":"Bioinformatics"},{"key":"pone.0252096.ref053","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v011.i09","article-title":"kernlab\u2013An S4 Package for Kernel Methods in R","volume":"11","author":"A Karatzoglou","year":"2004","journal-title":"Journal of Statistical Software"},{"key":"pone.0252096.ref054","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v028.i05","article-title":"Building predictive models in R using the caret package","volume":"28","author":"M Kuhn","year":"2008","journal-title":"Journal of Statistical Software"},{"key":"pone.0252096.ref055","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1071\/RD03073","article-title":"Towards an embryocentric world: the current and potential uses of embryo technologies in dairy production","volume":"16","author":"PJ Hansen","year":"2004","journal-title":"Reprod Fertil Dev"},{"key":"pone.0252096.ref056","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1002\/mrd.1153","article-title":"Consequences of bovine oocyte maturation, fertilization or early embryo development in vitro versus in vivo: implications for blastocyst yield and blastocyst quality","volume":"61","author":"D Rizos","year":"2002","journal-title":"Mol Reprod Dev"},{"key":"pone.0252096.ref057","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.ydbio.2014.12.005","article-title":"Tissue mechanics and adhesion during embryo development","volume":"401","author":"JH Shawky","year":"2015","journal-title":"Dev Biol"},{"key":"pone.0252096.ref058","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.semcdb.2019.11.018","article-title":"Towards a structural understanding of the remodeling of the actin cytoskeleton","volume":"102","author":"F Merino","year":"2020","journal-title":"Semin Cell Dev Biol"},{"key":"pone.0252096.ref059","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1002\/jmor.20010","article-title":"Focal adhesion kinase localizes to sites of cell-to-cell contact in vivo and increases apically in rat uterine luminal epithelium and the blastocyst at the time of implantation","volume":"273","author":"Y Kaneko","year":"2012","journal-title":"J Morphol"},{"key":"pone.0252096.ref060","first-page":"752","article-title":"Cell adhesion: the \u2018ins\u2019 and \u2018outs\u2019 of integrin signalling","volume":"14","author":"KH Wrighton","year":"2013","journal-title":"Nat Rev Mol Cell Biol"},{"key":"pone.0252096.ref061","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1186\/s12864-018-4826-3","article-title":"Genome-wide DNA methylation patterns of bovine blastocysts derived from in vivo embryos subjected to in vitro culture before, during or after embryonic genome activation","volume":"19","author":"D Salilew-Wondim","year":"2018","journal-title":"BMC Genomics"},{"key":"pone.0252096.ref062","doi-asserted-by":"crossref","first-page":"e0223753","DOI":"10.1371\/journal.pone.0223753","article-title":"Hyaluronic acid and epidermal growth factor improved the bovine embryo quality by regulating the DNA methylation and expression patterns of the focal adhesion pathway","volume":"14","author":"M Saeed-Zidane","year":"2019","journal-title":"PLoS One"},{"key":"pone.0252096.ref063","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1083\/jcb.147.3.611","article-title":"Focal adhesion kinase mediates the integrin signaling requirement for growth factor activation of MAP kinase","volume":"147","author":"MW Renshaw","year":"1999","journal-title":"J Cell Biol"},{"key":"pone.0252096.ref064","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.theriogenology.2008.11.007","article-title":"Effect of addition of hyaluronan to embryo culture medium on survival of bovine embryos in vitro following vitrification and establishment of pregnancy after transfer to recipients","volume":"71","author":"J Block","year":"2009","journal-title":"Theriogenology"},{"key":"pone.0252096.ref065","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nbt.1533","article-title":"Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells","volume":"27","author":"MP Ball","year":"2009","journal-title":"Nat Biotechnol"},{"key":"pone.0252096.ref066","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13072-018-0205-1","article-title":"Consistent inverse correlation between DNA methylation of the first intron and gene expression across tissues and species","volume":"11","author":"D Anastasiadi","year":"2018","journal-title":"Epigenetics Chromatin"},{"key":"pone.0252096.ref067","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3402\/jev.v2i0.20360","article-title":"Standardization of sample collection, isolation and analysis methods in extracellular vesicle research","volume":"2","author":"KW Witwer","year":"2013","journal-title":"J Extracell Vesicles"},{"key":"pone.0252096.ref068","doi-asserted-by":"crossref","first-page":"e58502","DOI":"10.1371\/journal.pone.0058502","article-title":"Endometrial exosomes\/microvesicles in the uterine microenvironment: a new paradigm for embryo-endometrial cross talk at implantation","volume":"8","author":"YH Ng","year":"2013","journal-title":"PLoS One"},{"key":"pone.0252096.ref069","doi-asserted-by":"crossref","first-page":"e0178306","DOI":"10.1371\/journal.pone.0178306","article-title":"Identification and characteristics of extracellular vesicles from bovine blastocysts produced in vitro","volume":"12","author":"EA Mellisho","year":"2017","journal-title":"PLoS One"},{"key":"pone.0252096.ref070","doi-asserted-by":"crossref","first-page":"e0158278","DOI":"10.1371\/journal.pone.0158278","article-title":"Induction of IFNT-Stimulated Genes by Conceptus-Derived Exosomes during the Attachment Period","volume":"11","author":"K Nakamura","year":"2016","journal-title":"PLoS One"},{"key":"pone.0252096.ref071","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.3390\/ijms21031163","article-title":"Extracellular Vesicles Mediated Early Embryo-Maternal Interactions","volume":"21","author":"A Bridi","year":"2020","journal-title":"Int J Mol Sci"},{"key":"pone.0252096.ref072","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1016\/j.bbrc.2017.11.176","article-title":"Intrauterine exosomes are required for bovine conceptus implantation","volume":"495","author":"K Kusama","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"key":"pone.0252096.ref073","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.theriogenology.2016.04.037","article-title":"Pivotal periods for pregnancy loss during the first trimester of gestation in lactating dairy cows","volume":"86","author":"MC Wiltbank","year":"2016","journal-title":"Theriogenology"},{"key":"pone.0252096.ref074","doi-asserted-by":"crossref","first-page":"3975","DOI":"10.1096\/fj.14-253112","article-title":"The WNT signaling antagonist Dickkopf-1 directs lineage commitment and promotes survival of the preimplantation embryo","volume":"28","author":"AC Denicol","year":"2014","journal-title":"FASEB J"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0252096","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,4]],"date-time":"2023-11-04T03:20:50Z","timestamp":1699068050000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0252096"}},"subtitle":[],"editor":[{"given":"Peter J.","family":"Hansen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,5,24]]},"references-count":74,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0252096","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,24]]}}}