{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T23:09:54Z","timestamp":1783465794662,"version":"3.55.0"},"reference-count":52,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T00:00:00Z","timestamp":1552003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["project AGL2013\u201348121-C3-R and AGL2016\u201379321-C2\u20132-R"],"award-info":[{"award-number":["project AGL2013\u201348121-C3-R and AGL2016\u201379321-C2\u20132-R"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The use of polyphenols is a promising strategy for preventing or alleviating intrauterine growth restriction (IUGR) because polyphenol supplementation increases plasma antioxidant capacity and improves oxidative stress at the feto-placental unit; which are recognized as main issues in IUGR. However, there is a scarcity of experimental data on both realistic benefits and potential hazards of polyphenol supplementation during gestation. Hence, we aimed to use a swine model of IUGR pregnancy to determine possible effects of maternal supplementation with polyphenols (hydroxytyrosol) on placental expression of genes involved in antioxidant homeostasis, vascularization and fetal growth and thus on antioxidant status, DNA-methylation and phenotypic traits (morphology and homeostasis) of the fetus. Hydroxytyrosol improves placental gene expression and fetal antioxidant status and glucose metabolism in a sex-dependent manner, in which males were favored in spite of developmental failures. Concomitantly, hydroxytyrosol prevented hypomethylation of DNA associated with oxidative stress. Finally, no major deleterious effects of hydroxytyrosol supplementation on constriction of the ductus arteriosus, a possible secondary effect of polyphenols during pregnancy, were found.<\/jats:p>","DOI":"10.3390\/ijms20051187","type":"journal-article","created":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T11:21:59Z","timestamp":1552044119000},"page":"1187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Polyphenols and IUGR Pregnancies: Effects of Maternal Hydroxytyrosol Supplementation on Placental Gene Expression and Fetal Antioxidant Status, DNA-Methylation and Phenotype"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4624-2585","authenticated-orcid":false,"given":"Consolaci\u00f3n","family":"Garcia-Contreras","sequence":"first","affiliation":[{"name":"Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria (INIA), Ctra. de La Coru\u00f1a Km. 7,5, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8916-2086","authenticated-orcid":false,"given":"Marta","family":"Vazquez-Gomez","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Universidad Complutense de Madrid (UCM), Ciudad Universitaria s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Barbero","sequence":"additional","affiliation":[{"name":"Diagnostic Imaging Service, Universidad Alfonso X El Sabio, 28691 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5669-6014","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Pesantez","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria (INIA), Ctra. de La Coru\u00f1a Km. 7,5, 28040 Madrid, Spain"},{"name":"School of Veterinary Medicine and Zootechnics, Faculty of Agricultural Sciences, University of Cuenca, Avda. Doce de Octubre, 010220 Cuenca, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8396-0968","authenticated-orcid":false,"given":"Angelo","family":"Zinellu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43\/B, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2500-8063","authenticated-orcid":false,"given":"Fiammetta","family":"Berlinguer","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Sassari, Via Vienna 2, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Gonzalez-A\u00f1over","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Universidad Complutense de Madrid (UCM), Ciudad Universitaria s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Micros Veterinaria, Campus de Vegazana, 24007 Leon, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Encinas","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Universidad Complutense de Madrid (UCM), Ciudad Universitaria s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Torres-Rovira","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria (INIA), Ctra. de La Coru\u00f1a Km. 7,5, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"Nu\u00f1ez","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria (INIA), Ctra. de La Coru\u00f1a Km. 7,5, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Ballesteros","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria (INIA), Ctra. de La Coru\u00f1a Km. 7,5, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Ayuso","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Veterinary Morphology, Department of Veterinary Sciences, Faculty of Biomedical, Pharmaceutical and Veterinary Sciences, University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9718-0903","authenticated-orcid":false,"given":"Susana","family":"Astiz","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria (INIA), Ctra. de La Coru\u00f1a Km. 7,5, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Isabel","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Universidad Complutense de Madrid (UCM), Ciudad Universitaria s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5738-8435","authenticated-orcid":false,"given":"Cristina","family":"Ovilo","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria (INIA), Ctra. de La Coru\u00f1a Km. 7,5, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0917-4475","authenticated-orcid":false,"given":"Antonio","family":"Gonzalez-Bulnes","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria (INIA), Ctra. de La Coru\u00f1a Km. 7,5, 28040 Madrid, Spain"},{"name":"Faculty of Veterinary Medicine, Universidad Complutense de Madrid (UCM), Ciudad Universitaria s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"399","DOI":"10.2174\/138955708783955926","article-title":"Biological and pharmacological activities of iridoids: Recent developments","volume":"8","author":"Tundis","year":"2008","journal-title":"Mini Rev. 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