{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:04:04Z","timestamp":1785420244120,"version":"3.56.0"},"reference-count":43,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"crossref","award":["202001650006"],"award-info":[{"award-number":["202001650006"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"crossref"}]},{"award":["202001650006"],"award-info":[{"award-number":["202001650006"]}],"id":[{"id":"https:\/\/ror.org\/04atp4p48","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Placental inflammation and dysfunction play critical roles in adverse pregnancy outcomes, including preeclampsia and intrauterine growth restriction. Exposure to environmental factors, such as dietary toxins, infectious agents, and pollution, is thought to increase the risk of these outcomes. Despite the widespread use of HTR-8\/SVneo and BeWo cells as trophoblast models, their comparative sensitivity to maternal exposome-related stimuli has not been systematically evaluated within the same experimental framework. we examined the responses of HTR-8\/SVneo and BeWo trophoblast cell lines to mycotoxin deoxynivalenol (DON), an inflammatory cytokine cocktail (CC; TNF-\u03b1, IL-1\u03b2, IFN-\u03b3), and particulate matter (PM2.5). Cells were seeded with either 0.2% or 1% penicillin\/streptomycin (P\/S) and exposed for 24 h. Cytokine secretion (IL-6 and IL-8), human chorionic gonadotropin (hCG) production, and mRNA and protein expression of junctional markers (ZO-1, OCLD, CLDN-3, CLDN-4, E-CAD) were analysed. DON significantly increased IL-6 secretion in both cell lines and elevated IL-8 levels in HTR-8\/SVneo cells only. DON suppressed hCG production in both cell lines. CC exposure markedly elevated IL-6 and IL-8 levels, particularly in HTR-8\/SVneo cells, without affecting hCG level. PM exposure did not significantly alter IL-6, IL-8, or hCG levels in either cell line. DON and CC altered the mRNA and protein expression of junctional markers in BeWo cells(ZO-1, OCLD, CLDN-3,CLDN-4), whereas HTR-8\/SVneo cells showed more limited changes. Most cellular responses were consistent across both P\/S concentrations. HTR-8\/SVneo and BeWo cells exhibit differential sensitivity to DON, CC, and PM2.5, underscoring the importance of cell model selection in in vitro placental toxicology research. These results provide a comparative framework for interpreting trophoblast responses to maternal exposome-related stimuli and highlight the need for functional validation in future studies.<\/jats:p>","DOI":"10.3390\/ijms27146434","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T09:32:54Z","timestamp":1784539974000},"page":"6434","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Deoxynivalenol, Cytokines, and Particulate Matter on Human Trophoblast Cells"],"prefix":"10.3390","volume":"27","author":[{"given":"Deguang","family":"Liu","sequence":"first","affiliation":[{"name":"Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8678-9182","authenticated-orcid":false,"given":"Johan","family":"Garssen","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands"},{"name":"Danone Research & Innovation, 3584 CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9961-750X","authenticated-orcid":false,"given":"Betty C. 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J. Physiol.-Cell Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1006\/excr.1993.1139","article-title":"Establishment and Characterization of First Trimester Human Trophoblast Cells with Extended Lifespan","volume":"206","author":"Graham","year":"1993","journal-title":"Exp. Cell Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1080\/10408398.2019.1571479","article-title":"Global Occurrence of Deoxynivalenol in Food Commodities and Exposure Risk Assessment in Humans in the Last Decade: A Survey","volume":"60","author":"Mishra","year":"2020","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1080\/10408398.2021.1954598","article-title":"The Toxicity Mechanisms of DON to Humans and Animals and Potential Biological Treatment Strategies","volume":"63","author":"Hou","year":"2023","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"110235","DOI":"10.1016\/j.foodcont.2023.110235","article-title":"Food Security, Underestimated Hazard of Joint Mycotoxin Exposure and Management of the Risk of Mycotoxin Contamination","volume":"159","author":"Stoev","year":"2024","journal-title":"Food Control"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1007\/s00204-022-03288-0","article-title":"Assessment of Multiple Mycotoxin Exposure and Its Association with Food Consumption: A Human Biomonitoring Study in a Pregnant Cohort in Rural Bangladesh","volume":"96","author":"Kyei","year":"2022","journal-title":"Arch. Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.fct.2013.08.043","article-title":"Urinary Analysis Reveals High Deoxynivalenol Exposure in Pregnant Women from Croatia","volume":"62","author":"Warth","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1080\/19440049.2010.551301","article-title":"Deoxynivalenol Exposure Assessment in a Cohort of Pregnant Women from Bradford, UK","volume":"29","author":"Hepworth","year":"2012","journal-title":"Food Addit. Contam. Part-Chem. Anal. Control Expo. Risk Assess."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Wells, L., Hardie, L., Williams, C., White, K., Liu, Y., De Santis, B., Debegnach, F., Moretti, G., Greetham, S., and Brera, C. (2016). Determination of Deoxynivalenol in the Urine of Pregnant Women in the UK. Toxins, 8.","DOI":"10.3390\/toxins8110306"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1016\/j.fct.2011.05.016","article-title":"Deoxynivalenol Transport across the Human Placental Barrier","volume":"49","author":"Nielsen","year":"2011","journal-title":"Food Chem. Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"R151","DOI":"10.1530\/REP-13-0232","article-title":"Influence of Infection during Pregnancy on Fetal Development","volume":"146","author":"McAdams","year":"2013","journal-title":"Reproduction"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1093\/ije\/dyab199","article-title":"Common Maternal Infections during Pregnancy and Childhood Leukaemia in the Offspring: Findings from Six International Birth Cohorts","volume":"51","author":"He","year":"2022","journal-title":"Int. J. Epidemiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Daskalakis, G., Psarris, A., Koutras, A., Fasoulakis, Z., Prokopakis, I., Varthaliti, A., Karasmani, C., Ntounis, T., Domali, E., and Theodora, M. (2023). Maternal Infection and Preterm Birth: From Molecular Basis to Clinical Implications. Children, 10.","DOI":"10.3390\/children10050907"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.it.2022.01.007","article-title":"Maternal Inflammation and Its Ramifications on Fetal Neurodevelopment","volume":"43","author":"Kwon","year":"2022","journal-title":"Trends Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.envint.2014.10.005","article-title":"A Review on the Human Health Impact of Airborne Particulate Matter","volume":"74","author":"Kim","year":"2015","journal-title":"Environ. Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1161\/CIR.0b013e3181dbece1","article-title":"Particulate Matter Air Pollution and Cardiovascular Disease: An Update to the Scientific Statement From the American Heart Association","volume":"121","author":"Brook","year":"2010","journal-title":"Circulation"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e804","DOI":"10.1016\/S2542-5196(22)00200-5","article-title":"Maternal Exposure to Ambient Black Carbon Particles and Their Presence in Maternal and Fetal Circulation and Organs: An Analysis of Two Independent Population-Based Observational Studies","volume":"6","author":"Bongaerts","year":"2022","journal-title":"Lancet Planet. Health"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"017010","DOI":"10.1289\/EHP11257","article-title":"Accumulation of Black Carbon Particles in Placenta, Cord Blood, and Childhood Urine in Association with the Intestinal Microbiome Diversity and Composition in Four- to Six-Year-Old Children in the ENVIRONAGE Birth Cohort","volume":"131","author":"Hogervorst","year":"2023","journal-title":"Environ. Health Perspect."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3109\/15569541003598553","article-title":"An Overview of Mycotoxin Contamination in Foods and Its Implications for Human Health","volume":"29","author":"Reddy","year":"2010","journal-title":"Toxin Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.foodcont.2018.12.014","article-title":"Deoxynivalenol in Cereal-Based Baby Food Production Process. A Review","volume":"99","author":"Pascari","year":"2019","journal-title":"Food Control"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3845","DOI":"10.3390\/toxins7103845","article-title":"Deoxynivalenol Exposure Assessment for Pregnant Women in Bangladesh","volume":"7","author":"Ali","year":"2015","journal-title":"Toxins"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.toxlet.2008.04.016","article-title":"The Effect of Feeding a Diet Naturally Contaminated with Deoxynivalenol (DON) and Zearalenone (ZON) on the Spleen and Liver of Sow and Fetus from Day 35 to 70 of Gestation","volume":"179","author":"Tiemann","year":"2008","journal-title":"Toxicol. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.toxlet.2007.04.003","article-title":"On the Transfer of the Fusarium Toxins Deoxynivalenol (DON) and Zearalenone (ZON) from Sows to Their Fetuses during Days 35\u201370 of Gestation","volume":"171","author":"Goyarts","year":"2007","journal-title":"Toxicol. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sayyari, A., Uhlig, S., F\u00e6ste, C.K., Framstad, T., and Sivertsen, T. (2018). Transfer of Deoxynivalenol (DON) through Placenta, Colostrum and Milk from Sows to Their Offspring during Late Gestation and Lactation. Toxins, 10.","DOI":"10.3390\/toxins10120517"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Seyed Toutounchi, N., Hogenkamp, A., Varasteh, S., Garssen, J., Folkerts, G., and Braber, S. (2019). Fusarium Mycotoxins Disrupt the Barrier and Induce IL-6 Release in a Human Placental Epithelium Cell Line. Toxins, 11.","DOI":"10.3390\/toxins11110665"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Viloti\u0107, A., Nacka-Aleksi\u0107, M., Pirkovi\u0107, A., Boji\u0107-Trbojevi\u0107, \u017d., Dekanski, D., and Jovanovi\u0107 Krivoku\u0107a, M. (2022). IL-6 and IL-8: An Overview of Their Roles in Healthy and Pathological Pregnancies. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314574"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1159\/000514898","article-title":"Interleukin-6 in Amniotic Fluid: A Reliable Marker for Adverse Outcomes in Women in Preterm Labor and Intact Membranes","volume":"48","year":"2021","journal-title":"Fetal Diagn. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1080\/10408444.2019.1629873","article-title":"Maternal Blood Biomarkers and Adverse Pregnancy Outcomes: A Systematic Review and Meta-Analysis","volume":"49","author":"Gomes","year":"2019","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.cytogfr.2020.12.004","article-title":"The Determinant Role of IL-6 in the Establishment of Inflammation Leading to Spontaneous Preterm Birth","volume":"59","author":"Prairie","year":"2021","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.siny.2006.05.001","article-title":"Inflammation in Preterm and Term Labour and Delivery","volume":"11","author":"Romero","year":"2006","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1146\/annurev-immunol-032712-100003","article-title":"Immunology of the Maternal-Fetal Interface","volume":"31","author":"Erlebacher","year":"2013","journal-title":"Annu. Rev. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1055\/s-2001-13910","article-title":"Effects of Human Chorionic Gonadotropin on Trophoblast Invasion","volume":"19","author":"Islami","year":"2001","journal-title":"Semin. Reprod. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.taap.2010.03.012","article-title":"Deoxynivalenol Affects In Vitro Intestinal Epithelial Cell Barrier Integrity through Inhibition of Protein Synthesis","volume":"245","author":"Sergent","year":"2010","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1053\/plac.1999.0494","article-title":"Production of Interleukin (IL)-6 and IL-8 by a Choriocarcinoma Cell Line, BeWo","volume":"21","author":"Fujisawa","year":"2000","journal-title":"Placenta"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1039\/C6FO01592A","article-title":"Yogurt Inhibits Intestinal Barrier Dysfunction in Caco-2 Cells by Increasing Tight Junctions","volume":"8","author":"Putt","year":"2017","journal-title":"Food Funct."},{"key":"ref_36","first-page":"e78829","article-title":"Regionally Distinct Trophoblast Regulate Barrier Function and Invasion in the Human Placenta","volume":"12","author":"Marsh","year":"2023","journal-title":"eLife"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s10815-024-03036-6","article-title":"Unraveling the Molecular Mechanisms Driving Enhanced Invasion Capability of Extravillous Trophoblast Cells: A Comprehensive Review","volume":"41","author":"Lin","year":"2024","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Wei, X.W., Zhang, Y.C., Wu, F., Tian, F.J., and Lin, Y. (2022). The Role of Extravillous Trophoblasts and Uterine NK Cells in Vascular Remodeling during Pregnancy. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.951482"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4115","DOI":"10.4049\/jimmunol.1601175","article-title":"Extravillous Trophoblast and Endothelial Cell Crosstalk Mediates Leukocyte Infiltration to the Early Remodeling Decidual Spiral Arteriole Wall","volume":"198","author":"Choudhury","year":"2017","journal-title":"J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Familari, M., N\u00e4\u00e4v, \u00c5., Erlandsson, L., Ishanska, A., Stamataki, Z., and Hansson, S.R. (2019). Exposure of Trophoblast Cells to Fine Particulate Matter Air Pollution Leads to Growth Inhibition, Inflammation and ER Stress. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0218799"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"N\u00e4\u00e4v, \u00c5., Erlandsson, L., Isaxon, C., \u00c5kesson, A., and Hansson, S.R. (2020). Urban PM2.5 Induces Cellular Toxicity, Hormone Dysregulation, Oxidative Damage, Inflammation, and Mitochondrial Interference in the HRT8 Trophoblast Cell Line. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00075"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.reprotox.2017.08.014","article-title":"Fine Particulate Matter Exposure Induces Cell Cycle Arrest and Inhibits Migration and Invasion of Human Extravillous Trophoblast, as Determined by an iTRAQ-Based Quantitative Proteomics Strategy","volume":"74","author":"Qin","year":"2017","journal-title":"Reprod. Toxicol."},{"key":"ref_43","first-page":"172403","article-title":"Gestational Exposure to PM2.5 Disrupts Fetal Development by Suppressing Placental Trophoblast Syncytialization via Progranulin\/mTOR Signaling","volume":"912","author":"Zhang","year":"2024","journal-title":"Sci. Total Environ."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6434\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:23:56Z","timestamp":1784694236000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6434"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":43,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27146434"],"URL":"https:\/\/doi.org\/10.3390\/ijms27146434","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]}}}