{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T11:02:39Z","timestamp":1783162959053,"version":"3.54.6"},"reference-count":135,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ARC linkage Scholarship","award":["ARC LP160101854"],"award-info":[{"award-number":["ARC LP160101854"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Abnormal uterine function affects conception rate and embryo development, thereby leading to poor fertility and reproduction failure. Exosomes are a nanosized subclass of extracellular vesicles (EV) that have important functions as intercellular communicators. They contain and carry transferable bioactive substances including micro RNA (miRNA) for target cells. Elements of the cargo can provide epigenetic modifications of the recipient cells and may have crucial roles in mechanisms of reproduction. The dairy industry accounts for a substantial portion of the economy of many agricultural countries. Exosomes can enhance the expression of inflammatory mediators in the endometrium, which contribute to various inflammatory diseases in transition dairy cows. This results in reduced fertility which leads to reduced milk production and increased cow maintenance costs. Thus, gaining a clear knowledge of exosomal epigenetic modifiers is critical to improving the breeding success and profitability of dairy farms. This review provides a brief overview of how exosomal miRNA contributes to inflammatory diseases and hence to poor fertility, particularly in dairy cows.<\/jats:p>","DOI":"10.3390\/ijms21239106","type":"journal-article","created":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T10:26:12Z","timestamp":1606731972000},"page":"9106","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Role of Exosomal Epigenetic Modifiers in Cell Communication and Fertility of Dairy Cows"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9354-352X","authenticated-orcid":false,"given":"Pevindu","family":"Abeysinghe","sequence":"first","affiliation":[{"name":"Institute of Health and Biomedical Innovation\u2014Centre for Children\u2019s Health Research, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD 4029, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2641-2295","authenticated-orcid":false,"given":"Natalie","family":"Turner","sequence":"additional","affiliation":[{"name":"Institute of Health and Biomedical Innovation\u2014Centre for Children\u2019s Health Research, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD 4029, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Morean Garcia","sequence":"additional","affiliation":[{"name":"Institute of Health and Biomedical Innovation\u2014Centre for Children\u2019s Health Research, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD 4029, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman","family":"Mosaad","sequence":"additional","affiliation":[{"name":"Institute of Health and Biomedical Innovation\u2014Centre for Children\u2019s Health Research, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD 4029, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassendrini N.","family":"Peiris","sequence":"additional","affiliation":[{"name":"Institute of Health and Biomedical Innovation\u2014Centre for Children\u2019s Health Research, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD 4029, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6167-7176","authenticated-orcid":false,"given":"Murray D.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Institute of Health and Biomedical Innovation\u2014Centre for Children\u2019s Health Research, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD 4029, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1017\/S0962728600002220","article-title":"The impact of genetic selection for increased milk yield on the welfare of dairy cows","volume":"19","author":"Oltenacu","year":"2010","journal-title":"Anim. Welf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1017\/S1751731108002358","article-title":"Integration of physiological mechanisms that influence fertility in dairy cows","volume":"2","author":"Garnsworthy","year":"2008","journal-title":"Animal"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1023\/B:VERC.0000014131.34839.4c","article-title":"Transition cow: Interaction with fertility","volume":"27","author":"Formigoni","year":"2003","journal-title":"Vet. Res. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.theriogenology.2010.12.024","article-title":"Relationships between cytology, bacteriology and vaginal discharge scores and reproductive performance in dairy cattle","volume":"76","author":"McDougall","year":"2011","journal-title":"Theriogenology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1051\/vetres:2004030","article-title":"The evaluation of non-specific immune status of heifers in field conditions during the periparturient period","volume":"35","author":"Piccinini","year":"2004","journal-title":"Vet. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3754","DOI":"10.3168\/jds.2018-15602","article-title":"Symposium review: Mechanisms of disruption of fertility by infectious diseases of the reproductive tract","volume":"102","author":"Gilbert","year":"2019","journal-title":"J. Dairy Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.3168\/jds.S0022-0302(85)80997-8","article-title":"Enhanced reproduction and its economic implications","volume":"68","author":"Britt","year":"1985","journal-title":"J. Dairy Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.3168\/jds.2010-3758","article-title":"Effects of postpartum uterine diseases on milk production and culling in dairy cows","volume":"94","author":"Dubuc","year":"2011","journal-title":"J. Dairy Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"102624","DOI":"10.1016\/j.jri.2019.102624","article-title":"Exosomes from dairy cows of divergent fertility; Action on endometrial cells","volume":"137","author":"Koh","year":"2020","journal-title":"J. Reprod. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13879","DOI":"10.1038\/s41598-019-50244-7","article-title":"Circulating exosomes may identify biomarkers for cows at risk for metabolic dysfunction","volume":"9","author":"Almughlliq","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Salomon, C., Kobayashi, M., Ashman, K., Sobrevia, L., Mitchell, M.D., and Rice, G.E. (2013). Hypoxia-induced changes in the bioactivity of cytotrophoblast-derived exosomes. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0079636"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4083","DOI":"10.1002\/pmic.200800109","article-title":"Proteomic profiling of exosomes: Current perspectives","volume":"8","author":"Simpson","year":"2008","journal-title":"Proteomics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1586\/epr.09.17","article-title":"Exosomes: Proteomic insights and diagnostic potential","volume":"6","author":"Simpson","year":"2009","journal-title":"Expert Rev. Proteom."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9143","DOI":"10.3168\/jds.2017-13261","article-title":"Effect of exosomes from plasma of dairy cows with or without an infected uterus on prostaglandin production by endometrial cell lines","volume":"100","author":"Almughlliq","year":"2017","journal-title":"J. Dairy Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6462","DOI":"10.3168\/jds.2017-14190","article-title":"Proteome profiling of exosomes derived from plasma of heifers with divergent genetic merit for fertility","volume":"101","author":"Koh","year":"2018","journal-title":"J. Dairy Sci."},{"key":"ref_16","first-page":"372","article-title":"Exosomes contain a selective number of mRNA and microRNA","volume":"62","author":"Valadi","year":"2007","journal-title":"Allergy"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.bbalip.2013.10.004","article-title":"Exosomes as new vesicular lipid transporters involved in cell-cell communication and various pathophysiologies","volume":"1841","author":"Record","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7661","DOI":"10.3168\/jds.2015-10786","article-title":"Short communication: Proteins from circulating exosomes represent metabolic state in transition dairy cows","volume":"99","author":"Crookenden","year":"2016","journal-title":"J. Dairy Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.canlet.2015.10.020","article-title":"Bovine milk-derived exosomes for drug delivery","volume":"371","author":"Munagala","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_20","first-page":"432","article-title":"Feto-Maternal trafficking of exosomes in murine pregnancy models","volume":"7","author":"Lei","year":"2016","journal-title":"Front. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10560","DOI":"10.3168\/jds.2019-17951","article-title":"Early-lactation diseases and fertility in 2 seasons of calving across US dairy herds","volume":"103","author":"Pinedo","year":"2020","journal-title":"J. Dairy Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2527\/1999.77suppl_2101x","article-title":"Inflammation in the bovine female reproductive tract","volume":"77","author":"Bondurant","year":"1999","journal-title":"J. Anim. Sci."},{"key":"ref_23","unstructured":"Tizard, I.R. (1996). Hypersensitivity. Veterinary Immunology: An Introduction, W. B. Saunders Co."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"589","DOI":"10.21451\/1984-3143-AR1002","article-title":"Impact and mechanisms of inflammatory diseases on embryonic development and fertility in cattle","volume":"14","author":"Ribeiro","year":"2017","journal-title":"Anim. Reprod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1146\/annurev-animal-020518-115227","article-title":"Tolerance and innate immunity shape the development of postpartum uterine disease and the impact of endometritis in dairy cattle","volume":"7","author":"Sheldon","year":"2019","journal-title":"Annu. Rev. Anim. Biosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"104635","DOI":"10.1016\/j.tiv.2019.104635","article-title":"Thiamethoxam induces meiotic arrest and reduces the quality of oocytes in cattle","volume":"61","author":"Nie","year":"2019","journal-title":"Toxicol. Vitr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"539","DOI":"10.21451\/1984-3143-AR2019-0057","article-title":"Inflammation: Friend or foe of bovine reproduction?","volume":"16","author":"Chastant","year":"2019","journal-title":"Anim. Reprod."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0021-9258(17)34997-9","article-title":"The biological significance of the thromboplastic protein of blood","volume":"166","author":"Chargaff","year":"1946","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1111\/j.1365-2141.1967.tb08741.x","article-title":"The nature and significance of platelet products in human plasma","volume":"13","author":"Wolf","year":"1967","journal-title":"Br. J. Haematol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1161\/CIRCRESAHA.113.300636","article-title":"Exosomes: Nanoparticles involved in cardioprotection?","volume":"114","author":"Yellon","year":"2014","journal-title":"Circ. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7590","DOI":"10.3168\/jds.2016-11060","article-title":"Plasma exosome profiles from dairy cows with divergent fertility phenotypes","volume":"99","author":"Mitchell","year":"2016","journal-title":"J. Dairy Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.theriogenology.2018.03.024","article-title":"Proteomic content of circulating exosomes in dairy cows with or without uterine infection","volume":"114","author":"Almughlliq","year":"2018","journal-title":"Theriogenology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13578-019-0282-2","article-title":"Exosomes: Biogenesis, biologic function and clinical potential","volume":"9","author":"Zhang","year":"2019","journal-title":"Cell Biosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1111\/j.1476-5381.2010.00724.x","article-title":"Transfer of the glycosylphosphatidylinositol-anchored 5\u2019-nucleotidase CD73 from adiposomes into rat adipocytes stimulates lipid synthesis","volume":"160","author":"Muller","year":"2010","journal-title":"Br. J. Pharm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1042\/bj20031594","article-title":"Mast cell- and dendritic cell-derived display a specific lipid composition and an unusual membrane organization","volume":"380","author":"Laulagnier","year":"2004","journal-title":"Biochem. J."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Pieters, B.C., Arntz, O.J., Bennink, M.B., Broeren, M.G., van Caam, A.P., Koenders, M.I., van Lent, P.L., van den Berg, W.B., de Vries, M., and van der Kraan, P.M. (2015). Commercial cow milk contains physically stable extracellular vesicles expressing immunoregulatory TGF-beta. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0121123"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s12986-016-0101-2","article-title":"Milk miRNAs: Simple nutrients or systemic functional regulators?","volume":"13","author":"Melnik","year":"2016","journal-title":"Nutr. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.semcdb.2015.02.010","article-title":"Extracellular vesicles in cancer: Exosomes, microvesicles and the emerging role of large oncosomes","volume":"40","author":"Minciacchi","year":"2015","journal-title":"Semin. Cell Dev. Biol"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.placenta.2014.02.009","article-title":"Intercellular communication by exosomes in placenta: A possible role in cell fusion?","volume":"35","author":"Record","year":"2014","journal-title":"Placenta"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.devcel.2011.05.015","article-title":"The ESCRT pathway","volume":"21","author":"Henne","year":"2011","journal-title":"Dev. Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.15252\/embj.201592484","article-title":"ESCRTs are everywhere","volume":"34","author":"Hurley","year":"2015","journal-title":"EMBO J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.semcancer.2014.04.009","article-title":"Sorting it out: Regulation of exosome loading","volume":"28","author":"Baixauli","year":"2014","journal-title":"Semin. Cancer Biol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Airola, M.V., and Hannun, Y.A. (2013). Sphingolipid metabolism and neutral sphingomyelinases. Handb. Exp. Pharm., 57\u201376.","DOI":"10.1007\/978-3-7091-1368-4_3"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"11649","DOI":"10.1074\/jbc.M112.445304","article-title":"The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes","volume":"288","author":"Jorge","year":"2013","journal-title":"J. Biol Chem"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.addr.2012.06.011","article-title":"Exosomes as nucleic acid nanocarriers","volume":"65","author":"Dassler","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1038\/ki.2010.278","article-title":"Exosomes\/microvesicles as a mechanism of cell-to-cell communication","volume":"78","author":"Camussi","year":"2010","journal-title":"Kidney Int."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.ceb.2009.03.007","article-title":"Exosomes--vesicular carriers for intercellular communication","volume":"21","author":"Simons","year":"2009","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1002\/jcb.22733","article-title":"Visualizing of the cellular uptake and intracellular trafficking of exosomes by live-cell microscopy","volume":"111","author":"Tian","year":"2010","journal-title":"J. Cell Biochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.semcdb.2015.02.009","article-title":"Exosomes and their roles in immune regulation and cancer","volume":"40","author":"Greening","year":"2015","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1002\/pmic.201400234","article-title":"Extracellular vesicles including exosomes are mediators of signal transduction: Are they protective or pathogenic?","volume":"15","author":"Gangoda","year":"2015","journal-title":"Proteomics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/ncomms1285","article-title":"Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells","volume":"2","author":"Mittelbrunn","year":"2011","journal-title":"Nat. Commun"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/1479-5876-12-162","article-title":"Exosomal miRNAs as potential biomarkers of cardiovascular risk in children","volume":"12","author":"Khalyfa","year":"2014","journal-title":"J. Transl. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.biochi.2013.06.016","article-title":"Emerging concepts on the role of exosomes in lipid metabolic diseases","volume":"96","author":"Record","year":"2014","journal-title":"Biochimie"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/978-1-4939-3999-2_3","article-title":"Exosomes in tumor angiogenesis","volume":"1464","author":"Salem","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"26589","DOI":"10.1074\/jbc.R116.757955","article-title":"Exosomes in the pathology of neurodegenerative diseases","volume":"291","author":"Howitt","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1186\/s12967-016-0927-4","article-title":"Exosomes in the nose induce immune cell trafficking and harbour an altered protein cargo in chronic airway inflammation","volume":"14","author":"Lasser","year":"2016","journal-title":"J. Transl. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1084\/jem.183.3.1161","article-title":"B lymphocytes secrete antigen-presenting vesicles","volume":"183","author":"Raposo","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.immuni.2014.08.008","article-title":"MicroRNA-containing T-regulatory-cell-derived exosomes suppress pathogenic T helper 1 cells","volume":"41","author":"Okoye","year":"2014","journal-title":"Immunity"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1002\/eji.201242909","article-title":"CD73 expression on extracellular vesicles derived from CD4+ CD25+ Foxp3+ T cells contributes to their regulatory function","volume":"43","author":"Smyth","year":"2013","journal-title":"Eur. J. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"676","DOI":"10.4049\/jimmunol.1003884","article-title":"Cancer exosomes express CD39 and CD73, which suppress T cells through adenosine production","volume":"187","author":"Clayton","year":"2011","journal-title":"J. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/nm0598-594","article-title":"Eradication of established murine tumors using a novel cell-free vaccine: Dendritic cell-derived exosomes","volume":"4","author":"Zitvogel","year":"1998","journal-title":"Nat. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/cmi.2010.59","article-title":"CD4(+) T cell-released exosomes inhibit CD8(+) cytotoxic T-lymphocyte responses and antitumor immunity","volume":"8","author":"Zhang","year":"2011","journal-title":"Cell Mol. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Cressatti, M., Galindez, J.M., Juwara, L., Orlovetskie, N., Velly, A.M., Eintracht, S., Liberman, A., Gornitsky, M., and Schipper, H.M. (2020). Characterization and heme oxygenase-1 content of extracellular vesicles in human biofluids. J. Neurochem.","DOI":"10.1111\/jnc.15167"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"554","DOI":"10.3389\/fcell.2020.00554","article-title":"Discovery of exosomes from tick saliva and salivary glands reveals therapeutic roles for CXCL12 and IL-8 in wound healing at the tick-human skin interface","volume":"8","author":"Zhou","year":"2020","journal-title":"Front. Cell Dev. Biol"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Yokoyama, S., Takeuchi, A., Yamaguchi, S., Mitani, Y., Watanabe, T., Matsuda, K., Hotta, T., Shively, J.E., and Yamaue, H. (2017). Clinical implications of carcinoembryonic antigen distribution in serum exosomal fraction-measurement by ELISA. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0183337"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Palacios, A., Sampedro, L., Sevilla, I.A., Molina, E., Gil, D., Azkargorta, M., Elortza, F., Garrido, J.M., Anguita, J., and Prados-Rosales, R. (2019). Mycobacterium tuberculosis extracellular vesicle-associated lipoprotein LpqH as a potential biomarker to distinguish paratuberculosis infection or vaccination from tuberculosis infection. BMC Vet. Res., 15.","DOI":"10.1186\/s12917-019-1941-6"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Banliat, C., Le Bourhis, D., Bernardi, O., Tomas, D., Labas, V., Salvetti, P., Guyonnet, B., Mermillod, P., and Saint-Dizier, M. (2020). Oviduct fluid extracellular vesicles change the phospholipid composition of bovine embryos developed in vitro. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155326"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"223","DOI":"10.3892\/br.2016.824","article-title":"Circulating osteocyte-derived exosomes contain miRNAs which are enriched in exosomes from MLO-Y4 cells","volume":"6","author":"Sato","year":"2017","journal-title":"Biomed. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/ncb1596","article-title":"Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells","volume":"9","author":"Valadi","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Ishikawa, H., Rahman, M.M., Yamauchi, M., Takashima, S., Wakihara, Y., Kamatari, Y.O., Shimizu, K., Okada, A., and Inoshima, Y. (2020). mRNA profile in milk extracellular vesicles from bovine leukemia virus-infected cattle. Viruses, 12.","DOI":"10.3390\/v12060669"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Chen, T., Xi, Q.-Y., Sun, J.-J., Ye, R.-S., Cheng, X., Sun, R.-P., Wang, S.-B., Shu, G., Wang, L.-N., and Zhu, X.-T. (2017). Revelation of mRNAs and proteins in porcine milk exosomes by transcriptomic and proteomic analysis. BMC Vet. Res., 13.","DOI":"10.1186\/s12917-017-1021-8"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.3168\/jds.2014-9076","article-title":"Bovine milk exosomes contain microRNA and mRNA and are taken up by human macrophages","volume":"98","author":"Izumi","year":"2015","journal-title":"J. Dairy Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.bbagrm.2015.10.010","article-title":"Discovery and functional analysis of lncRNAs: Methodologies to investigate an uncharacterized transcriptome","volume":"1859","author":"Kashi","year":"2016","journal-title":"Biochim Biophys Acta"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"s363","DOI":"10.1017\/S1751731118001337","article-title":"Review: Epigenetics, developmental programming and nutrition in herbivores","volume":"12","author":"Velazquez","year":"2018","journal-title":"Animal"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s12943-018-0880-3","article-title":"Exosome\u2013transmitted long non-coding RNA PTENP1 suppresses bladder cancer progression","volume":"17","author":"Zheng","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s00425-020-03480-5","article-title":"Long non-coding RNAs in plants: Emerging modulators of gene activity in development and stress responses","volume":"252","author":"Chen","year":"2020","journal-title":"Planta"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"194417","DOI":"10.1016\/j.bbagrm.2019.194417","article-title":"Non-coding RNA regulatory networks","volume":"1863","author":"Panni","year":"2020","journal-title":"Biochim. Biophys. Acta. Gene. Regul. Mech."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"6726","DOI":"10.3168\/jds.2019-16257","article-title":"Exploration of long noncoding RNA in bovine milk exosomes and their stability during digestion in vitro","volume":"102","author":"Zeng","year":"2019","journal-title":"J. Dairy Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/nature02871","article-title":"The functions of animal microRNAs","volume":"431","author":"Ambros","year":"2004","journal-title":"Nature"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/nrg1379","article-title":"MicroRNAs: Small RNAs with a big role in gene regulation","volume":"5","author":"He","year":"2004","journal-title":"Nat. Rev. Genet."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/nature03817","article-title":"Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis","volume":"436","author":"Zhao","year":"2005","journal-title":"Nature"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1038\/nature03552","article-title":"A microRNA polycistron as a potential human oncogene","volume":"435","author":"He","year":"2005","journal-title":"Nature"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1126\/science.1091903","article-title":"MicroRNAs modulate hematopoietic lineage differentiation","volume":"303","author":"Chen","year":"2004","journal-title":"Science"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/nature03076","article-title":"A pancreatic islet-specific microRNA regulates insulin secretion","volume":"432","author":"Poy","year":"2004","journal-title":"Nature"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"118","DOI":"10.7150\/ijbs.8.118","article-title":"Immune-related microRNAs are abundant in breast milk exosomes","volume":"8","author":"Zhou","year":"2012","journal-title":"Int. J. Biol. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3168\/jds.2019-16880","article-title":"Complexity of the microRNA transcriptome of cow milk and milk-derived extracellular vesicles isolated via differential ultracentrifugation","volume":"103","author":"Benmoussa","year":"2020","journal-title":"J. Dairy Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.bbrc.2010.04.135","article-title":"Isolation of bovine milk-derived microvesicles carrying mRNAs and microRNAs","volume":"396","author":"Hata","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1021\/jf505526w","article-title":"Loss of miRNAs during processing and storage of cow\u2019s (Bos taurus) milk","volume":"63","author":"Howard","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s13238-013-2119-9","article-title":"Immune modulatory function of abundant immune-related microRNAs in microvesicles from bovine colostrum","volume":"4","author":"Sun","year":"2013","journal-title":"Protein Cell"},{"key":"ref_90","first-page":"797","article-title":"Excavation of a buried treasure--DNA, mRNA, miRNA and protein analysis in formalin fixed, paraffin embedded tissues","volume":"26","author":"Klopfleisch","year":"2011","journal-title":"Histol. Histopathol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s12033-011-9427-1","article-title":"MicroRNA expression profiling in archival tissue specimens: Methods and data processing","volume":"50","author":"Streichert","year":"2012","journal-title":"Mol. Biotechnol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1021\/acs.jafc.6b05002","article-title":"Fermentation results in quantitative changes in milk-derived exosomes and different effects on cell growth and survival","volume":"65","author":"Yu","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s13238-012-2003-z","article-title":"Horizontal transfer of microRNAs: Molecular mechanisms and clinical applications","volume":"3","author":"Chen","year":"2012","journal-title":"Protein Cell"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1210\/jc.2012-2415","article-title":"Circulating microRNAs identified in a genome-wide serum microRNA expression analysis as noninvasive biomarkers for endometriosis","volume":"98","author":"Wang","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1093\/humrep\/des413","article-title":"Plasma miR-17-5p, miR-20a and miR-22 are down-regulated in women with endometriosis","volume":"28","author":"Jia","year":"2013","journal-title":"Hum. Reprod."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1071\/AN18579","article-title":"The frontiers of biomedical science and its application to animal science in addressing the major challenges facing Australasian dairy farming","volume":"60","author":"Mitchell","year":"2020","journal-title":"Anim. Prod. Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/1477-7827-11-78","article-title":"MicroRNAs expression profiling of eutopic proliferative endometrium in women with ovarian endometriosis","volume":"11","author":"Laudanski","year":"2013","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12958-017-0319-5","article-title":"Integration analysis of microRNA and mRNA paired expression profiling identifies deregulated microRNA-transcription factor-gene regulatory networks in ovarian endometriosis","volume":"16","author":"Zhao","year":"2018","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3966","DOI":"10.1016\/j.febslet.2009.10.036","article-title":"Correlation of mRNA and protein in complex biological samples","volume":"583","author":"Maier","year":"2009","journal-title":"FEBS Lett."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1158\/1055-9965.EPI-10-0064","article-title":"Comparison of mRNA and protein measures of cytokines following vaccination with human papillomavirus-16 L1 virus-like particles","volume":"19","author":"Shebl","year":"2010","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Rametse, C.L., Adefuye, A.O., Olivier, A.J., Curry, L., Gamieldien, H., Burgers, W.A., Lewis, D.A., Williamson, A.-L., Katz, A.A., and Passmore, J.-A.S. (2018). Inflammatory cytokine profiles of semen influence cytokine responses of cervicovaginal epithelial cells. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02721"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"R41","DOI":"10.1530\/REP-14-0163","article-title":"Innate immunity and inflammation of the bovine female reproductive tract in health and disease","volume":"148","author":"Sheldon","year":"2014","journal-title":"Reproduction"},{"key":"ref_103","first-page":"804","article-title":"MiR-145 suppresses embryo-epithelial juxtacrine communication at implantation by modulating maternal IGF1R","volume":"128","author":"Kang","year":"2015","journal-title":"J. Cell Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1071\/RD12097","article-title":"MicroRNA-199a mediates mucin 1 expression in mouse uterus during implantation","volume":"26","author":"Inyawilert","year":"2014","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.repbio.2019.06.003","article-title":"Exosome-derived uterine microRNAs isolated from cows with endometritis impede blastocyst development","volume":"19","author":"Wang","year":"2019","journal-title":"Reprod. Biol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Sohel, M.M., Hoelker, M., Noferesti, S.S., Salilew-Wondim, D., Tholen, E., Looft, C., Rings, F., Uddin, M.J., Spencer, T.E., and Schellander, K. (2013). Exosomal and non-exosomal transport of extra-cellular micrornas in follicular fluid: Implications for bovine oocyte developmental competence. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0078505"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.tvjl.2007.12.031","article-title":"Uterine diseases in cattle after parturition","volume":"176","author":"Sheldon","year":"2008","journal-title":"Vet. J."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1111\/1751-7915.13565","article-title":"Exosome-derived uterine miR-218 isolated from cows with endometritis regulates the release of cytokines and chemokines","volume":"13","author":"Wang","year":"2020","journal-title":"Microb. Biotechnol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Gao, P., Wang, D., Liu, M., Chen, S., Yang, Z., Zhang, J., Wang, H., Niu, Y., Wang, W., and Yang, J. (2020). DNA methylation-mediated repression of exosomal miR-652-5p expression promotes oesophageal squamous cell carcinoma aggressiveness by targeting PARG and VEGF pathways. PLoS Genet., 16.","DOI":"10.1371\/journal.pgen.1008592"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nrd3978","article-title":"Extracellular vesicles: Biology and emerging therapeutic opportunities","volume":"12","author":"Breakefield","year":"2013","journal-title":"Nat. Reviews. Drug Discov."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"649161","DOI":"10.1155\/2015\/649161","article-title":"The Role of Extracellular Vesicles: An Epigenetic View of the Cancer Microenvironment","volume":"2015","author":"Qian","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e184","DOI":"10.1038\/ctg.2016.40","article-title":"BARHL2 methylation using gastric wash dna or gastric juice exosomal dna is a useful marker for early detection of gastric cancer in anh. pylori-independent manner","volume":"7","author":"Yamamoto","year":"2016","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1038\/leu.2014.51","article-title":"BCR-ABL1\u2013positive microvesicles transform normal hematopoietic transplants through genomic instability: Implications for donor cell leukemia","volume":"28","author":"Zhu","year":"2014","journal-title":"Leukemia"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"6999","DOI":"10.1038\/ncomms7999","article-title":"Chip-based analysis of exosomal mRNA mediating drug resistance in glioblastoma","volume":"6","author":"Shao","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.mrrev.2011.04.002","article-title":"Epigenetics, spermatogenesis and male infertility","volume":"727","author":"Rajender","year":"2011","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/em.22242","article-title":"In vitro exposure to CPF affects bovine sperm epigenetic gene methylation pattern and the ability of sperm to support fertilization and embryo development","volume":"60","author":"Pallotta","year":"2019","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1080\/15592294.2019.1582217","article-title":"Comparative analyses of sperm DNA methylomes among human, mouse and cattle provide insights into epigenomic evolution and complex traits","volume":"14","author":"Fang","year":"2019","journal-title":"Epigenetics"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.theriogenology.2018.11.001","article-title":"Promoter methylation and expression analysis of Bvh gene in bulls with varying semen motility parameters","volume":"125","author":"Ahlawat","year":"2019","journal-title":"Theriogenology"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1080\/15592294.2020.1738026","article-title":"Promoter hypermethylation of PIWI\/piRNA pathway genes associated with diminished pachytene piRNA production in bovine hybrid male sterility","volume":"15","author":"Zhang","year":"2020","journal-title":"Epigenetics"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Capra, E., Lazzari, B., Turri, F., Cremonesi, P., Portela, A.M.R., Ajmone-Marsan, P., Stella, A., and Pizzi, F. (2019). Epigenetic analysis of high and low motile sperm populations reveals methylation variation in satellite regions within the pericentromeric position and in genes functionally related to sperm DNA organization and maintenance in Bos taurus. BMC Genom., 20.","DOI":"10.1186\/s12864-019-6317-6"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"557846","DOI":"10.3389\/fgene.2020.557846","article-title":"Parental Effects on Epigenetic Programming in Gametes and Embryos of Dairy Cows","volume":"11","author":"Wu","year":"2020","journal-title":"Front. Genet."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"8575","DOI":"10.1038\/s41598-020-65479-y","article-title":"Identification of prognostic signature of non-small cell lung cancer based on TCGA methylation data","volume":"10","author":"Wang","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.jtbi.2014.05.019","article-title":"Bioinformatic analysis revealing association of exosomal mRNAs and proteins in epigenetic inheritance","volume":"357","author":"Sharma","year":"2014","journal-title":"J. Theor. Biol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.3892\/ijo.2013.2115","article-title":"Oligodendroglioma cells synthesize the differentiation-specific linker histone H1\u02da and release it into the extracellular environment through shed vesicles","volume":"43","author":"Schiera","year":"2013","journal-title":"Int. J. Oncol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1189\/jlb.0103010","article-title":"Inhibition of myeloid cell differentiation in cancer: The role of reactive oxygen species","volume":"74","author":"Kusmartsev","year":"2003","journal-title":"J. Leukoc. Biol."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Ugur, M.R., Kutchy, N.A., Menezes, E.B.D., Ul-Husna, A., Haynes, B.P., Uzun, A., Kaya, A., Topper, E., Moura, A., and Memili, E. (2019). Retained acetylated histone four in bull sperm associated with fertility. Front. Vet. Sci., 6.","DOI":"10.3389\/fvets.2019.00223"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Hundertmark, T., G\u00e4rtner, S.M.K., Rathke, C., and Renkawitz-Pohl, R. (2018). Nejire\/dCBP-mediated histone H3 acetylation during spermatogenesis is essential for male fertility in Drosophila melanogaster. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0203622"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Kutchy, N.A., Menezes, E.S.B., Chiappetta, A., Tan, W., Wills, R.W., Kaya, A., Topper, E., Moura, A.A., Perkins, A.D., and Memili, E. (2018). Acetylation and methylation of sperm histone 3 lysine 27 (H3K27ac and H3K27me3) are associated with bull fertility. Andrologia, 50.","DOI":"10.1111\/and.12915"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"13766","DOI":"10.1038\/s41598-018-31822-7","article-title":"Metabolic gene expression and epigenetic effects of the ketone body \u03b2-hydroxybutyrate on H3K9ac in bovine cells, oocytes and embryos","volume":"8","author":"Sangalli","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"180158","DOI":"10.1098\/rsob.180158","article-title":"The histone deacetylase NlHDAC1 regulates both female and male fertility in the brown planthopper, Nilaparvata lugens","volume":"8","author":"Zhang","year":"2018","journal-title":"Open Biol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.devcel.2019.10.024","article-title":"Gcn5-Mediated Histone Acetylation Governs Nucleosome Dynamics in Spermiogenesis","volume":"51","author":"Luense","year":"2019","journal-title":"Dev. Cell"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"115253","DOI":"10.1016\/j.taap.2020.115253","article-title":"The ubiquitination and acetylation of histones are associated with male reproductive disorders induced by chronic exposure to arsenite","volume":"408","author":"Wu","year":"2020","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.rbmo.2018.05.014","article-title":"Cocaine alters the mouse testicular epigenome with direct impact on histone acetylation and DNA methylation marks","volume":"37","author":"Pantoja","year":"2018","journal-title":"Reprod. Biomed. Online"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1080\/14789450.2019.1693895","article-title":"Post-translational modifications of seminal proteins and their importance in male fertility potential","volume":"16","author":"Maciel","year":"2019","journal-title":"Expert Rev. Proteom."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s10815-018-1354-7","article-title":"Histone modification signatures in human sperm distinguish clinical abnormalities","volume":"36","author":"Schon","year":"2019","journal-title":"J. Assist. Reprod. Genet."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/23\/9106\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:39:32Z","timestamp":1760179172000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/23\/9106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,30]]},"references-count":135,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["ijms21239106"],"URL":"https:\/\/doi.org\/10.3390\/ijms21239106","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,30]]}}}