{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:35:49Z","timestamp":1753893349852,"version":"3.41.2"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T00:00:00Z","timestamp":1626652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>Deoxynivalenol (DON) is a mycotoxin that contaminates various plant materials. Exposure to DON can disrupt hormonal homeostasis, decrease body weight gains and modulate the immune system in pigs. It can also cause diarrhea, vomiting, leukocytosis, hemorrhaging or even death. Prolonged exposure to low doses of DON can have serious health implications in mammals. This is the first <jats:italic>in vivo<\/jats:italic> study to show that <jats:italic>per os<\/jats:italic> administration of low DON doses probably contributes to specific dysfunctions in steroidogenesis processes by inducing the immunohistochemical expression of estrogen receptors alpha (ER\u03b1) in the entire gastrointestinal tract in strongly stained cells (3 points) and estrogen receptors beta (ER\u03b2), but only in both investigated segments of the duodenum in pre-pubertal gilts. Therefore, the aim of this study was to determine whether a NOAEL dose of DON (12 \u03bcg DON\/kg BW) administered <jats:italic>per os<\/jats:italic> over a period of 42 days induces changes in the immunohistochemical expression of ER in different intestinal segments and the transcriptional activation of <jats:italic>CYP1A1<\/jats:italic> and <jats:italic>GSTP1<\/jats:italic> genes in the large intestine of pre-pubertal gilts. This is the first report to demonstrate the expression of ER, in particular ER\u03b2, with the associated consequences. The expression of ER was accompanied by considerable variations in the activation of <jats:italic>CYP1A1<\/jats:italic> and <jats:italic>GSTP1<\/jats:italic> genes, but it supported the maintenance of a stable consensus between the degree of mycotoxin exposure and the detoxifying effect in pre-pubertal gilts.<\/jats:p>","DOI":"10.3389\/fvets.2021.644549","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T08:05:19Z","timestamp":1626681919000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["The Effect of 42-Day Exposure to a Low Deoxynivalenol Dose on the Immunohistochemical Expression of Intestinal ERs and the Activation of CYP1A1 and GSTP1 Genes in the Large Intestine of Pre-pubertal Gilts"],"prefix":"10.3389","volume":"8","author":[{"given":"Magdalena","family":"Gaj\u0119cka","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawe\u0142","family":"Brzuzan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iwona","family":"Otrocka-Domaga\u0142a","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u0141ukasz","family":"Zielonka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylwia","family":"Lisieska-\u017bo\u0142nierczyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maciej T.","family":"Gaj\u0119cki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.fct.2016.07.033","article-title":"Endocrine activity of mycotoxins and mycotoxin mixtures","volume":"96","author":"Demaegdt","year":"2016","journal-title":"Food Chem Toxicol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1002\/jat.3623","article-title":"Deoxynivalenol as potential modulator of human steroidogenesis","volume":"33","author":"Urbanek","year":"2018","journal-title":"J Appl Toxicol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"561","DOI":"10.3390\/toxins11100561","article-title":"Imbalance in the blood concentrations of selected steroids in prepubertal gilts depending on the time of exposure to low doses of zearalenone","volume":"11","author":"Rykaczewska","year":"2019","journal-title":"Toxins."},{"key":"B4","doi-asserted-by":"publisher","first-page":"144","DOI":"10.3390\/toxins12030144","article-title":"The effect of different doses of zearalenone in feed on the bioavailability of zearalenone and alpha-zearalenol, and the concentrations of estradiol and testosterone in the peripheral blood of prepubertal gilts","volume":"12","author":"Zielonka","year":"2020","journal-title":"Toxins."},{"key":"B5","doi-asserted-by":"publisher","first-page":"727","DOI":"10.3390\/toxins11120727","article-title":"Co-occurrence of DON and emerging mycotoxins in worldwide finished pig feed and their combined toxicity in intestinal cells","volume":"11","author":"Khoshal","year":"2019","journal-title":"Toxins."},{"key":"B6","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.fct.2020.111161","article-title":"Toxicity of mycotoxins in vivo on vertebrate organisms: a review","volume":"137","author":"Cimbalo","year":"2020","journal-title":"Food Chem Toxicol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"610","DOI":"10.3390\/toxins12100610","article-title":"Mycotoxin deoxynivalenol has different impacts on intestinal barrier and stem cells by its route of exposure","volume":"12","author":"Hanyu","year":"2020","journal-title":"Toxins."},{"key":"B8","doi-asserted-by":"publisher","first-page":"733","DOI":"10.3390\/toxins11120733","article-title":"Deoxynivalenol induces inflammatory injury in IPEC-J2 cells via NF-_B signaling pathway","volume":"11","author":"Wang","year":"2019","journal-title":"Toxins."},{"key":"B9","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.toxicon.2019.11.006","article-title":"Correlation between the exposure of deoxynivalenol and zearalenone and the immunohistochemical expression of estrogen receptors in the intestinal epithelium and mRNA of selected colonic enzymes in prepubertal gilts","volume":"173","author":"Gaj\u0119cka","year":"2020","journal-title":"Toxicon."},{"key":"B10","doi-asserted-by":"publisher","first-page":"8709","DOI":"10.3390\/ijerph110908709","article-title":"Versatility or promiscuity: the estrogen receptors, control of ligand selectivity and an update on subtype selective ligands","volume":"11","author":"Ng","year":"2014","journal-title":"Int J Environ Res Public Health."},{"key":"B11","doi-asserted-by":"publisher","first-page":"179","DOI":"10.32463\/rphs.2019.v05i03.03","article-title":"A review on selective estrogen receptor modulators","volume":"5","author":"Bandolia","year":"2019","journal-title":"Res Pharm Health Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1517\/17460440903490395","article-title":"Discovery of estrogen receptor modulators: a review of virtual screening and SAR efforts","volume":"5","author":"Xu","year":"2010","journal-title":"Expert Opin Drug Discov."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2162","DOI":"10.3390\/cancers12082162","article-title":"Perspectives on the role of non-coding RNAs in the regulation of expression and function of the estrogen receptor","volume":"12","author":"Taheri","year":"2020","journal-title":"Cancers."},{"key":"B14","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1093\/toxsci\/kft164","article-title":"EADB: an estrogenic activity database for assessing potential endocrine activity","volume":"135","author":"Shen","year":"2013","journal-title":"Toxicol Sci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"3690","DOI":"10.3390\/ijms21103690","article-title":"Pharmacological modulation of steroid activity in hormone-dependent breast and prostate cancers: effect of some plant extract derivatives","volume":"21","author":"Bayala","year":"2020","journal-title":"Int J Mol Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2931","DOI":"10.1007\/s00204-016-1826-4","article-title":"Toxicology of deoxynivalenol and its acetylated and modified forms","volume":"90","author":"Payros","year":"2016","journal-title":"Arch Toxicol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.toxlet.2016.12.018","article-title":"Role of CYP1A1 in the biological activity of methylated resveratrol analogue, 3,4,5,40-tetramethoxystilbene (DMU-212) in ovarian cancer A-2780 and non-cancerous HOSE cells","volume":"267","author":"Piotrowska-Kempisty","year":"2017","journal-title":"Toxicol Lett."},{"key":"B18","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.ejmech.2016.02.061","article-title":"Identification of leads for antiproliferative activity on MDA-MB-435 human breast cancer cells through pharmacophore and CYP1A1-mediated metabolism","volume":"115","author":"Nandekar","year":"2016","journal-title":"Eur J Med Chem."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.3390\/nu11081741","article-title":"Glutathione transferase p1-1 an enzyme useful in biomedicine and as biomarker in clinical practice and in environmental pollution","volume":"11","author":"Bocedi","year":"2019","journal-title":"Nutrients."},{"key":"B20","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.gene.2017.01.034","article-title":"Energy landscape of a GSTP1 polymorph linked with cytological function decay in response to chemical stressors","volume":"609","author":"Basharat","year":"2017","journal-title":"Gene."},{"key":"B21","first-page":"289","article-title":"The occurrence of zearalenone and its derivatives in standard and therapeutic feeds for companion animals","volume":"7","author":"Zwierzchowski","year":"2004","journal-title":"Pol J Vet Sci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"973","DOI":"10.3390\/toxins6030973","article-title":"Deoxynivalenol in the gastrointestinal tract of immature gilts under per os toxin application","volume":"6","author":"Wa\u015bkiewicz","year":"2014","journal-title":"Toxins."},{"key":"B23","doi-asserted-by":"publisher","first-page":"3210","DOI":"10.3390\/toxins7083210","article-title":"Zearalenone in the intestinal tissues of immature gilts exposed per os to mycotoxins","volume":"7","author":"Zielonka","year":"2015","journal-title":"Toxins."},{"key":"B24","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.toxlet.2007.10.002","article-title":"Zero tolerances in food and animal feed-Are there any scientific alternatives? A European point of view on an international controversy","volume":"175","author":"Heberer","year":"2007","journal-title":"Toxicol Lett."},{"key":"B25","unstructured":"Commission Recommendation (2006\/576\/EC, 2006) of 17 August 2006 on the presence of deoxynivalenol, zearale-none, ochratoxin A, T-2 and HT-2 and fumonisins in products intended for animal feeding79Off J Eur Union.2006"},{"key":"B26","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1007\/BF03192202","article-title":"Biosynthesis, isolation, separation and purification of zearalenone, deoxynivalenol and 15-acetyldeoxynivalenol","author":"Kostecki","year":"1991","journal-title":"Mycotoxin Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1007\/BF03192203","article-title":"Biosynthesis, isolation, separation and purification of nivalenol, fusarenone-X and zearalenone","author":"Kostecki","year":"1991","journal-title":"Mycotoxin Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"685","DOI":"10.2478\/v10181-012-0106-3","article-title":"The effect of low-dose experimental zearalenone intoxication on the immunoexpression of estrogen receptors in the ovaries of pre-pubertal bitches","volume":"15","author":"Gaj\u0119cka","year":"2012","journal-title":"Pol J Vet Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"227","DOI":"10.4297\/najms.2011.3227","article-title":"E-cadherin as a diagnostic biomarker in breast cancer","volume":"3","author":"Singhai","year":"2011","journal-title":"N Am J Med Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1186\/1471-2105-13-134","article-title":"Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction","volume":"13","author":"Ye","year":"2012","journal-title":"BMC Bioinformatics."},{"key":"B31","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.aquatox.2011.07.018","article-title":"Endocrine and developmental effects in Atlantic salmon (Salmo salar) exposed to perfluorooctane sulfonic or perfluorooctane carboxylic acids","volume":"108","author":"Spachmo","year":"2012","journal-title":"Aquat Toxicol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"235","DOI":"10.2174\/1389200043335559","article-title":"Cytochrome P450 regulation and drug biotransformation during inflammation and infection","volume":"5","author":"Renton","year":"2004","journal-title":"Curr Drug Metab."},{"key":"B33","doi-asserted-by":"publisher","first-page":"18","DOI":"10.3390\/molecules22010018","article-title":"Activity of zearalenone in the porcine intestinal tract","volume":"22","author":"Gaj\u0119cka","year":"2017","journal-title":"Molecules."},{"key":"B34","doi-asserted-by":"publisher","first-page":"115166","DOI":"10.1016\/j.taap.2020.115166","article-title":"Epigenetic upregulation of galanin-like peptide mediates deoxynivalenol induced-growth inhibition in pituitary cells","volume":"403","author":"Liu","year":"2020","journal-title":"Toxicol Appl Pharm."},{"key":"B35","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.toxlet.2005.10.007","article-title":"Bioavailability of the fusarium toxin deoxynivalenol (DON) from naturally contaminated wheat for the pig","volume":"63","author":"Goyarts","year":"2006","journal-title":"Toxicol Lett."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2826","DOI":"10.1016\/j.fct.2008.05.016","article-title":"Tissue distribution and proinflammatory cytokine gene expression following acute oral exposure to deoxynivalenol: comparison of weanling and adult mice","volume":"46","author":"Pestka","year":"2008","journal-title":"Food Chem Toxicol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"190","DOI":"10.3390\/toxins12030190","article-title":"Minimal concentrations of deoxynivalenol reduce cytokine production in individual lymphocyte populations in pigs","volume":"12","author":"Hlavov\u00e1","year":"2020","journal-title":"Toxins."},{"key":"B38","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.virol.2012.04.009","article-title":"Porcine reproductive and respiratory syndrome virus induces CD4+CD8+CD25+Foxp3+ regulatory T cells (Tregs)","volume":"430","author":"Silva-Campa","year":"2012","journal-title":"Virology."},{"key":"B39","doi-asserted-by":"publisher","first-page":"557","DOI":"10.3390\/molecules21050557","article-title":"Changes in the subpopulations of porcine peripheral blood lymphocytes induced by exposure to low doses of zearalenone (ZEN) and deoxynivalenol (DON)","volume":"21","author":"Dabrowski","year":"2016","journal-title":"Molecules."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2064","DOI":"10.3390\/toxins6072064","article-title":"The effect of experimental Fusarium mycotoxicosis on microbiota diversity in porcine ascending colon contents","volume":"6","author":"Piotrowska","year":"2014","journal-title":"Toxins."},{"key":"B41","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.anifeedsci.2011.12.014","article-title":"Mycotoxin contamination of the feed supply chain: implications for animal productivity and feed security","volume":"173","author":"Bryden","year":"2012","journal-title":"Anim Feed Sci Tech."},{"key":"B42","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.toxlet.2018.09.007","article-title":"Impact of glutathione modulation on the toxicity of the Fusarium mycotoxins deoxynivalenol (DON), NX-3 and butenolide in human liver cells","volume":"299","author":"Woelflingseder","year":"2018","journal-title":"Toxicol Lett."},{"key":"B43","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1093\/toxsci\/kfs239","article-title":"Toxicity of deoxynivalenol and its acetylated derivatives on the intestine: differential effects on morphology, barrier function, tight junction proteins, and mitogen-activated protein kinases","volume":"130","author":"Pinton","year":"2012","journal-title":"Toxicol Sci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jsbmb.2016.01.009","article-title":"Disruption of steroidogenesis: cell models for mechanistic investigations and as screening tools","volume":"158","author":"Odermatt","year":"2016","journal-title":"J Steroid Biochem Mol Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"294","DOI":"10.3390\/ijms20020294","article-title":"Ginsenoside Rb1 blocks ritonavir-Induced oxidative stress and eNOS downregulation through activation of estrogen receptor-beta and upregulation of SOD in human endothelial cells","volume":"20","author":"L\u00fc","year":"2019","journal-title":"Int J Mol Sci."},{"key":"B46","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.canlet.2015.12.009","article-title":"Estrogen receptor beta as target for colorectal cancer prevention","volume":"372","author":"Williams","year":"2016","journal-title":"Cancer Lett."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.3390\/nu11081709","article-title":"Phytestrogens: dietary intake, bioavailability, and protective mechanisms against colorectal neoproliferative lesions","volume":"11","author":"Viggiani","year":"2019","journal-title":"Nutrients."},{"key":"B48","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.jsbmb.2014.08.003","article-title":"DHEA \u2013 a precursor of ER\u00df ligands","volume":"145","author":"Warner","year":"2015","journal-title":"J Steroid Biochem."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.3390\/toxins6051615","article-title":"Effect of deoxynivalenol and other type B trichothecenes on the intestine: a review","volume":"6","author":"Pinton","year":"2014","journal-title":"Toxins."},{"key":"B50","doi-asserted-by":"publisher","first-page":"148","DOI":"10.3390\/toxins10040148","article-title":"The effects of deoxynivalenol and zearalenone on the pig large intestine. A light and electron microscopic study","volume":"10","author":"Przybylska-Gornowicz","year":"2018","journal-title":"Toxins."},{"key":"B51","doi-asserted-by":"publisher","first-page":"769","DOI":"10.3390\/toxins12120769","article-title":"Mycotoxin and gut microbiota interactions","volume":"12","author":"Guerre","year":"2020","journal-title":"Toxins."},{"key":"B52","doi-asserted-by":"publisher","first-page":"2437","DOI":"10.1016\/j.humpath.2014.08.008","article-title":"Prognostic relevance of estrogen receptor-\u03b1 ser167 phosphorylation in stage II-III colon cancer patients","volume":"45","author":"L\u00f3pez-Calderero","year":"2014","journal-title":"Hum Pathol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/j.fct.2005.08.020","article-title":"Effect of various doses of deoxynivalenol on liver xenobiotic metabolizing enzymes in mice","volume":"44","author":"Gouze","year":"2006","journal-title":"Food Chem Toxicol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.mrgentox.2017.02.002","article-title":"CYP1A1 i462V polymorphism is associated with reduced genotoxicityin yeast despite positive association with increased cancer risk","volume":"815","author":"Freedland","year":"2017","journal-title":"Mut Res."},{"key":"B55","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1186\/s12917-015-0449-y","article-title":"Growth performance, serum biochemical profile, jejunal morphology, and the expression of nutrients transporter genes in deoxynivalenol (DON)- challenged growing pigs","volume":"11","author":"Wu","year":"2015","journal-title":"BMC Vet Res."},{"key":"B56","doi-asserted-by":"publisher","first-page":"347","DOI":"10.3390\/toxins10090347","article-title":"Colon microbiome of pigs fed diet contaminated with commercial purified deoxynivalenol and zearalenone","volume":"10","author":"Reddy","year":"2018","journal-title":"Toxins."}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2021.644549\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T08:05:25Z","timestamp":1626681925000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2021.644549\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,19]]},"references-count":56,"alternative-id":["10.3389\/fvets.2021.644549"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2021.644549","relation":{},"ISSN":["2297-1769"],"issn-type":[{"type":"electronic","value":"2297-1769"}],"subject":[],"published":{"date-parts":[[2021,7,19]]},"article-number":"644549"}}