{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T13:35:22Z","timestamp":1781098522216,"version":"3.54.1"},"reference-count":42,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T00:00:00Z","timestamp":1592438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"This work was supported by grants from the Institute for Maternal and Child Health, IRCCS \u201cBurlo Garofolo\u201d, Trieste, Italy","award":["RC20\/16, RC23\/18, RC24\/19"],"award-info":[{"award-number":["RC20\/16, RC23\/18, RC24\/19"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: An aberrant and persistent inflammatory state at the fetal-maternal interface is considered as a key contributor in compromised pregnancies. Decidual endothelial cells (DECs) play a pivotal role in the control of the local decidual inflammation. The aim of the current study was to determine whether dietary supplement with zinc oxide (ZnO), due to its very low adverse effects, may be useful for modulating the inflammatory response in the first trimester of pregnancy. Methods: The anti-inflammatory properties of ZnO in pregnancy were evaluated by in vitro tests on endothelial cells isolated from normal deciduas and on a trophoblast cell line (HTR8\/Svneo). The effects of this treatment were analyzed in terms of adhesion molecule expression and inflammatory cytokine secretion, by real time-quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Results: Our data showed that ZnO was able to reduce the inflammatory response of DECs, in terms of vascular cell adhesion molecule-1 (VCAM-1), interleukin (IL)-8, IL-6, tumor necrosis factor-\u03b1 (TNF-\u03b1) and monocyte chemoattractant protein-1 (MCP-1) expression induced by TNF-\u03b1 stimulation. This compound exerted no effect on intracellular adhesion molecule-1 (ICAM-1) exocytosis induced by TNF-\u03b1 on stimulated trophoblast cells, but significantly reduced their IL-6 expression. Conclusion: According to these results, it can be suggested that the ZnO supplement, through its modulation of the pro-inflammatory response of DECs, can be used in pregnancy for the prevention of local decidual inflammation.<\/jats:p>","DOI":"10.3390\/nu12061822","type":"journal-article","created":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T11:00:56Z","timestamp":1592478056000},"page":"1822","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Zinc Oxide Exerts Anti-Inflammatory Properties on Human Placental Cells"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5902-3205","authenticated-orcid":false,"given":"Andrea","family":"Balduit","sequence":"first","affiliation":[{"name":"Department of Life Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7910-1274","authenticated-orcid":false,"given":"Alessandro","family":"Mangogna","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8315-2258","authenticated-orcid":false,"given":"Chiara","family":"Agostinis","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health, IRCCS Burlo Garofolo, 34134 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7836-4934","authenticated-orcid":false,"given":"Gabriella","family":"Zito","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health, IRCCS Burlo Garofolo, 34134 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2157-8330","authenticated-orcid":false,"given":"Federico","family":"Romano","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health, IRCCS Burlo Garofolo, 34134 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8031-1102","authenticated-orcid":false,"given":"Giuseppe","family":"Ricci","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health, IRCCS Burlo Garofolo, 34134 Trieste, Italy"},{"name":"Department of Medical, Surgical and Health Science, University of Trieste, 34129 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1737-5776","authenticated-orcid":false,"given":"Roberta","family":"Bulla","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/j.1749-6632.2010.05938.x","article-title":"Inflammation and pregnancy: The role of the immune system at the implantation site","volume":"1221","author":"Mor","year":"2011","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.siny.2003.09.005","article-title":"Placental inflammation","volume":"9","author":"Redline","year":"2004","journal-title":"Semin Neonatol."},{"key":"ref_3","first-page":"253","article-title":"Bounds KR, Mitchell BM. Regulation of the Anti-Inflammatory Cytokines Interleukin-4 and Interleukin-10 during Pregnancy","volume":"27","author":"Chatterjee","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zev Williams (2012). Inducing Tolerance to Pregnancy. N. Eng. J. Med., 387, 1159\u20131181.","DOI":"10.1056\/NEJMcibr1207279"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Xu, Y., Plazyo, O., Romero, R., Hassan, S.S., and Gomez-Lopez, N. (2015). Isolation of Leukocytes from the Human Maternal-fetal Interface. J. Vis. Exp.","DOI":"10.3791\/52863-v"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"14847","DOI":"10.1038\/srep14847","article-title":"RelB activation in anti-inflammatory decidual endothelial cells: A master plan to avoid pregnancy failure?","volume":"5","author":"Masat","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jri.2009.06.124","article-title":"Complement production by trophoblast cells at the feto-maternal interface","volume":"82","author":"Bulla","year":"2009","journal-title":"J. Reprod. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1095\/biolreprod58.4.1003","article-title":"Expression of intercellular adhesion molecule-1 messenger ribonucleic acid and protein in human term placental cells and its modulation by pro-inflammatory cytokines (interleukin-1beta and tumor necrosis factor alpha)","volume":"58","author":"Gaffuri","year":"1998","journal-title":"Biol. Reprod."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Lundqvist (2014). Reported dietary intake in early pregnant compared to non-pregnant women\u2013A cross-sectional study. BMC Pregnancy Childbirth, 14.","DOI":"10.1186\/s12884-014-0373-3"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Marangoni, F., Cetin, I., Verduci, E., Canzone, G., Giovannini, M., Scollo, P., Corsello, G., and Poli, A. (2016). Maternal Diet and Nutrient Requirements in Pregnancy and Breastfeeding. An Italian Consensus Document. Nutrients, 8.","DOI":"10.3390\/nu8100629"},{"key":"ref_11","unstructured":"(2014, March 10). Nordic Nutrition Recommendations. Available online: https:\/\/norden.diva-portal.org\/smash\/get\/diva2:704251\/FULLTEXT01.pdf."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10427","DOI":"10.3390\/nu7125542","article-title":"Zinc in Early Life: A Key Element in the Fetus and Preterm Neonate","volume":"7","author":"Terrin","year":"2015","journal-title":"Nutrients"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/j.1365-3016.2012.01289.x","article-title":"Effect of zinc supplementation on pregnancy and infant outcomes: A systematic review","volume":"26","author":"Chaffee","year":"2012","journal-title":"Paediatr. Perinat Epidemiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/nrendo.2016.37","article-title":"Micronutrient deficiencies in pregnancy worldwide: Health effects and prevention","volume":"12","author":"Gernand","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/biof.91","article-title":"Zinc deficiency and neurodevelopment: The case of neurons","volume":"36","author":"Adamo","year":"2010","journal-title":"Biofactors"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"405","DOI":"10.3389\/fnmol.2018.00405","article-title":"Shank and Zinc Mediate an AMPA Receptor Subunit Switch in Developing Neurons","volume":"11","author":"Ha","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"224","DOI":"10.3945\/an.114.006874","article-title":"Zinc","volume":"6","author":"Huang","year":"2015","journal-title":"Adv. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"817S","DOI":"10.1093\/jn\/133.3.817S","article-title":"The need for maternal zinc supplementation in developing countries: An unresolved issue","volume":"133","author":"Osendarp","year":"2003","journal-title":"J. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"353","DOI":"10.2119\/2008-00033.Prasad","article-title":"Zinc in human health: Effect of zinc on immune cells","volume":"14","author":"Prasad","year":"2008","journal-title":"Mol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1093\/ajcn\/46.5.763","article-title":"Zinc and pregnancy outcome","volume":"46","author":"Swanson","year":"1987","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1152\/physrev.1985.65.2.238","article-title":"Absorption, transport, and hepatic metabolism of copper and zinc: Special reference to metallothionein and ceruloplasmin","volume":"65","author":"Cousins","year":"1985","journal-title":"Physiol. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1093\/ajcn\/40.5.1071","article-title":"A stable isotope study of zinc absorption in young men: Effects of phytate and alpha-cellulose","volume":"40","author":"Turnlund","year":"1984","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1016\/j.molimm.2007.12.025","article-title":"Decidual endothelial cells express surface-bound C1q as a molecular bridge between endovascular trophoblast and decidual endothelium","volume":"45","author":"Bulla","year":"2008","journal-title":"Mol. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2730","DOI":"10.2527\/1999.77102730x","article-title":"Bioavailability of zinc in several sources of zinc oxide, zinc sulfate, and zinc metal","volume":"77","author":"Edwards","year":"1999","journal-title":"J. Anim. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Maares, M., and Haase, H. (2020). A Guide to Human Zinc Absorption: General Overview and Recent Advances of In Vitro Intestinal Models. Nutrients, 12.","DOI":"10.3390\/nu12030762"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2591","DOI":"10.1096\/fasebj.6.8.1592209","article-title":"Cytokine regulation of endothelial cell function","volume":"6","author":"Mantovani","year":"1992","journal-title":"FASEB J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1016\/0092-8674(89)90775-7","article-title":"Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes","volume":"59","author":"Osborn","year":"1989","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/S0002-9378(99)70239-5","article-title":"Preeclampsia: An excessive maternal inflammatory response to pregnancy","volume":"180","author":"Redman","year":"1999","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1126\/science.1251816","article-title":"Preterm labor: One syndrome, many causes","volume":"345","author":"Romero","year":"2014","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"71","DOI":"10.5830\/CVJA-2016-009","article-title":"Pre-eclampsia: Its pathogenesis and pathophysiolgy","volume":"27","author":"Gathiram","year":"2016","journal-title":"Cardiovasc J. Afr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ejogrb.2020.03.026","article-title":"The effect of oral zinc supplementation on cervicovaginal lavage fluid zinc level","volume":"248","author":"Takacs","year":"2020","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wessels, I., Maywald, M., and Rink, L. (2017). Zinc as a Gatekeeper of Immune Function. Nutrients, 9.","DOI":"10.3390\/nu9121286"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Gammoh, N.Z., and Rink, L. (2017). Zinc in Infection and Inflammation. Nutrients, 9.","DOI":"10.20944\/preprints201705.0176.v1"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1084\/jem.176.6.1583","article-title":"Functional analysis of the human vascular cell adhesion molecule 1 promoter","volume":"176","author":"Neish","year":"1992","journal-title":"J. Exp. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Agostinis, C., Masat, E., Bossi, F., Ricci, G., Menegazzi, R., Lombardelli, L., Zito, G., Mangogna, A., Degan, M., and Gattei, V. (2019). Transcriptomics and Immunological Analyses Reveal a Pro-Angiogenic and Anti-Inflammatory Phenotype for Decidual Endothelial Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071604"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.autrev.2014.11.008","article-title":"Zinc and its role in immunity and inflammation","volume":"14","author":"Bonaventura","year":"2015","journal-title":"Autoimmun. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s10522-006-9060-8","article-title":"Simultaneous evaluation of circulating chemokine and cytokine profiles in elderly subjects by multiplex technology: Relationship with zinc status","volume":"7","author":"Mariani","year":"2006","journal-title":"Biogerontology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"676","DOI":"10.3390\/nu4070676","article-title":"Zinc and regulation of inflammatory cytokines: Implications for cardiometabolic disease","volume":"4","author":"Foster","year":"2012","journal-title":"Nutrients"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s10522-006-9046-6","article-title":"Inflammation, genes and zinc in ageing and age-related diseases","volume":"7","author":"Vasto","year":"2006","journal-title":"Biogerontology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/0002-9343(83)91205-6","article-title":"Abnormal zinc metabolism in type II diabetes mellitus","volume":"75","author":"Kinlaw","year":"1983","journal-title":"Am. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Prasad, A.S. (2014). Zinc: An antioxidant and anti-inflammatory agent: Role of zinc in degenerative disorders of aging. J. Trace Elem. Med. Biol.","DOI":"10.3389\/fnut.2014.00014"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ota, E., Mori, R., Middleton, P., Tobe-Gai, R., Mahomed, K., Miyazaki, C., and Bhutta, Z.A. (2015). Zinc supplementation for improving pregnancy and infant outcome. Cochrane Database Syst. Rev.","DOI":"10.1002\/14651858.CD000230.pub5"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/6\/1822\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:40:31Z","timestamp":1760175631000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/6\/1822"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,18]]},"references-count":42,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["nu12061822"],"URL":"https:\/\/doi.org\/10.3390\/nu12061822","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,18]]}}}