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A maternal diet high in fruit and vegetables lowers the risk of FGR but the association cannot be explained fully by known macro\u2010 and micronutrients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>This study investigates if dietary\u2010derived extracellular vesicles (EVs) can regulate placental function. The study characterizes the microRNA and protein cargo of EVs isolated from watermelon, show they are actively internalized by human intestinal epithelial cells in vitro, use mass spectrometry to demonstrate that they alter the intestinal secretome and bioinformatic analyses to predict the likely affected pathways in cells\/tissues distal to gut. Application of the watermelon EV\u2010modified intestinal secretome to human placental trophoblast cells and ex vivo tissue explants affects the trophoblast proteome and key aspects of trophoblast behavior, including migration and syncytialization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Dietary\u2010derived plant EVs can modify intestinal communication with distal tissues, including the placenta. Harnessing the beneficial properties of dietary\u2010derived plant EVs and\/or exploiting their potential as natural delivery agents may provide new ways to improve placental function and reduce rates of FGR.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.202200013","type":"journal-article","created":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T07:34:20Z","timestamp":1659944060000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Watermelon\u2010Derived Extracellular Vesicles Influence Human Ex Vivo Placental Cell Behavior by Altering Intestinal Secretions"],"prefix":"10.1002","volume":"66","author":[{"given":"Kate","family":"Timms","sequence":"first","affiliation":[{"name":"Maternal and Fetal Health Research Centre School of Medical Sciences University of Manchester  Manchester M13 9WL UK"},{"name":"Manchester University NHS Foundation Trust Manchester Academic Health Sciences Centre  Manchester M13 9WL UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Holder","sequence":"additional","affiliation":[{"name":"Department of Metabolism Digestion and Reproduction Institute of Reproductive and Developmental Biology Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Day","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Function School of Biological Sciences University of Manchester  Manchester M13 9PT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Mclaughlin","sequence":"additional","affiliation":[{"name":"Division of Diabetes Endocrinology and Gastroenterology University of Manchester  Manchester M13 9PT UK"},{"name":"Department of Gastroenterology Salford Royal NHS Foundation Trust  Salford M6 8HD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen A.","family":"Forbes","sequence":"additional","affiliation":[{"name":"Discovery and Translational Science Department Leeds Institute of Cardiovascular and Metabolic Medicine Faculty of Medicine and Health University of Leeds  Leeds LS2 9JT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9725-7010","authenticated-orcid":false,"given":"Melissa","family":"Westwood","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre School of Medical Sciences University of Manchester  Manchester M13 9WL UK"},{"name":"Manchester University NHS Foundation Trust Manchester Academic Health Sciences Centre  Manchester M13 9WL UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,19]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2018.02.002"},{"key":"e_1_2_9_2_1","first-page":"S5","volume":"52","author":"Onis M.","year":"1998","journal-title":"Eur. 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