{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T08:25:43Z","timestamp":1787127943765,"version":"build-2736575974"},"reference-count":198,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dioxins are persistent environmental pollutants with high lipophilicity and long half-lives, enabling their accumulation in biological tissues and ecosystems. Among them, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic and extensively studied chemical. Human exposure occurs primarily through contaminated food, cigarette smoke, and industrial emissions, posing significant health risks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This review summarizes the effects of dioxins, particularly TCDD, on craniofacial and dental development and discusses recent findings on the mechanisms underlying these effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A narrative review of experimental studies in animal models,\n                      <jats:italic>in vitro<\/jats:italic>\n                      systems, and human study data was conducted to evaluate phenotypic and mechanistic outcomes of TCDD exposure across palatogenesis, craniofacial bone formation, and tooth development.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the developing palate, TCDD impairs mesenchymal proliferation, shelf elevation, and fusion, resulting in cleft palate involving various mechanisms such as oxidative stress, apoptosis, epigenetic changes, and suppression of TGF-\u03b2 and Wnt signaling. Craniofacial bone development is also affected, with reduced ossification, altered mineralization, and impaired osteoblast differentiation. These outcomes are largely mediated by aberrant aryl hydrocarbon receptor (AhR) activation. However, other pathways, such as retinoic acid and vitamin D signaling, have also been found to have roles in these outcomes. Furthermore, genetic background modulates susceptibility, as shown by strain-specific differences and the protective role of AhR repressors. TCDD disrupts odontogenesis in a stage- and dose-dependent manner, leading to enamel hypoplasia, molar agenesis, dentin defects, and increased caries susceptibility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Dioxins, particularly TCDD, are potent developmental toxicants affecting multiple craniofacial tissues. Their effects are driven by dysregulation of several critical signaling pathways, with AhR acting as the central mediator. Given their long half-life and bioaccumulation, dioxins remain a relevant public health threat.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1878726","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T07:45:58Z","timestamp":1787125558000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Craniofacial and dental toxicity of dioxins: developmental phenotypes and mechanistic insights"],"prefix":"10.3389","volume":"14","author":[{"given":"Mohammadreza","family":"Vatankhah","sequence":"first","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Department of Biomedical Sciences, Herman Ostrow School of Dentistry, University of Southern California","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Department of Biomedical Sciences, Herman Ostrow School of Dentistry, University of Southern California","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/0041-008x(89)90011-2","article-title":"Cellular alterations and enhanced induction of cleft palate after coadministration of retinoic acid and TCDD","volume":"99","author":"Abbott","year":"1989","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/0041-008x(90)90337-t","article-title":"TCDD-induced altered expression of growth factors may have a role in producing cleft palate and enhancing the incidence of clefts after coadministration of retinoic acid and TCDD","volume":"106","author":"Abbott","year":"1990","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1002\/tera.1420400602","article-title":"Etiology of retinoic acid-induced cleft palate varies with the embryonic stage","volume":"40","author":"Abbott","year":"1989","journal-title":"Teratology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1002\/tera.1420450104","article-title":"Comparisons of the effects of TCDD and hydrocortisone on growth factor expression provide insight into their interaction in the embryonic mouse palate","volume":"45","author":"Abbott","year":"1992","journal-title":"Teratology"},{"key":"B5","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1006\/taap.1994.1085","article-title":"Ah receptor in embryonic mouse palate and effects of TCDD on receptor expression","volume":"126","author":"Abbott","year":"1994","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1093\/toxsci\/47.1.62","article-title":"AhR, ARNT, and CYP1A1 mRNA quantitation in cultured human embryonic palates exposed to TCDD and comparison with mouse palate in vivo and in culture","volume":"47","author":"Abbott","year":"1999","journal-title":"Toxicol. Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1093\/toxsci\/71.1.84","article-title":"EGF and TGF-alpha expression influence the developmental toxicity of TCDD: dose response and AhR phenotype in EGF, TGF-alpha, and EGF + TGF-alpha knockout mice","volume":"71","author":"Abbott","year":"2003","journal-title":"Toxicol. Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1002\/bdra.20133","article-title":"Effects of epidermal growth factor (EGF), transforming growth factor-alpha (TGFalpha), and 2,3,7,8-tetrachlorodibenzo-p-dioxin on fusion of embryonic palates in serum-free organ culture using wild-type, EGF knockout, and TGFalpha knockout mouse strains","volume":"73","author":"Abbott","year":"2005","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"cjaf003","DOI":"10.1093\/ejo\/cjaf003","article-title":"Influence of genetic and environmental factors on transverse growth","volume":"47","author":"Al-Obaidi","year":"2025","journal-title":"Eur. J. Orthod."},{"key":"B10","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1111\/j.1875-595x.2006.tb00336.x","article-title":"Developmental dental toxicity of dioxin and related compounds\u2013a review","volume":"56","author":"Alaluusua","year":"2006","journal-title":"Int. Dent. J."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0300-483x(93)90152-i","article-title":"Exposure to 2,3,7,8-tetrachlorodibenzo-para-dioxin leads to defective dentin formation and pulpal perforation in rat incisor tooth","volume":"81","author":"Alaluusua","year":"1993","journal-title":"Toxicology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/1382-6689(96)00007-5","article-title":"Polychlorinated dibenzo-p-dioxins and dibenzofurans via mother's milk may cause developmental defects in the child's teeth","volume":"1","author":"Alaluusua","year":"1996","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1289\/ehp.6920","article-title":"Developmental dental aberrations after the dioxin accident in Seveso","volume":"112","author":"Alaluusua","year":"2004","journal-title":"Environ. Health Perspect."},{"key":"B14","doi-asserted-by":"publisher","first-page":"R109","DOI":"10.1530\/jme-22-0076","article-title":"Aryl hydrocarbon receptor (AhR)-mediated signaling as a critical regulator of skeletal cell biology","volume":"69","author":"Alhamad","year":"2022","journal-title":"J. Mol. Endocrinol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1023\/a:1016693911300","article-title":"2,3,7,8-tetrachlorodibenzo-p-dioxin affects size and shape, but not asymmetry, of mandibles in mice","volume":"10","author":"Allen","year":"2001","journal-title":"Ecotoxicology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"9990","DOI":"10.1073\/pnas.152706299","article-title":"A constitutively active dioxin\/aryl hydrocarbon receptor induces stomach tumors","volume":"99","author":"Andersson","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B17","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/0048-9697(91)90005-y","article-title":"Atmospheric lifetimes of dibenzo-p-dioxins and dibenzofurans","volume":"104","author":"Atkinson","year":"1991","journal-title":"Sci. Total Environ."},{"key":"B18","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.toxlet.2003.12.062","article-title":"Aryl-hydrocarbon receptor-dependent pathway and toxic effects of TCDD in humans: a population-based study in Seveso, Italy","volume":"149","author":"Baccarelli","year":"2004","journal-title":"Toxicol. Lett."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.19191\/ep18.3-4.S1.P001.057","article-title":"Environmental and individual exposure and the risk of congenital anomalies: a review of recent epidemiological evidence","volume":"42","author":"Baldacci","year":"2018","journal-title":"Epidemiol. Prev."},{"key":"B20","doi-asserted-by":"publisher","first-page":"dev191064","DOI":"10.1242\/dev.191064","article-title":"Gene-environment interactions: aligning birth defects research with complex etiology","volume":"147","author":"Beames","year":"2020","journal-title":"Development"},{"key":"B21","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1289\/ehp.94102s9157","article-title":"The mechanism of dioxin toxicity: relationship to risk assessment","volume":"102","author":"Birnbaum","year":"1994","journal-title":"Environ. Health Perspect."},{"key":"B22","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/0041-008x(87)90328-0","article-title":"Teratogenicity of three polychlorinated dibenzofurans in C57BL\/6N mice","volume":"90","author":"Birnbaum","year":"1987","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2124","DOI":"10.1002\/j.1460-2075.1994.tb06488.x","article-title":"Cyclin D1 transgene impedes lymphocyte maturation and collaborates in lymphomagenesis with the myc gene","volume":"13","author":"Bodrug","year":"1994","journal-title":"Embo J."},{"key":"B24","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/j.scitotenv.2019.04.060","article-title":"Background levels of dioxin-like polychlorinated biphenyls (dlPCBs), polychlorinated, polybrominated and mixed halogenated dibenzo-p-dioxins and dibenzofurans (PCDD\/Fs, PBDD\/Fs and PXDD\/Fs) in sera of pregnant women in Accra, Ghana","volume":"673","author":"Bruce-Vanderpuije","year":"2019","journal-title":"Sci. Total Environ."},{"key":"B25","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.aquatox.2015.04.005","article-title":"Dioxin disrupts cranial cartilage and dermal bone development in zebrafish larvae","volume":"164","author":"Burns","year":"2015","journal-title":"Aquat. Toxicol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1242\/dev.067082","article-title":"Palatogenesis: morphogenetic and molecular mechanisms of secondary palate development","volume":"139","author":"Bush","year":"2012","journal-title":"Development"},{"key":"B27","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1093\/toxsci\/kfp021","article-title":"Dioxin-sensitive proteins in differentiating osteoblasts: effects on bone formation in vitro","volume":"108","author":"Carpi","year":"2009","journal-title":"Toxicol. Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1111\/j.1469-7580.2008.01014.x","article-title":"Current knowledge of tooth development: patterning and mineralization of the murine dentition","volume":"214","author":"Cat\u00f3n","year":"2009","journal-title":"J. Anat."},{"key":"B29","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.toxlet.2020.08.001","article-title":"Comparison of the biological behaviors of palatal mesenchymal and epithelial cells induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in vitro","volume":"333","author":"Chen","year":"2020","journal-title":"Toxicol. Lett."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2019","DOI":"10.1177\/15353702211012288","article-title":"Correlation between TGF-\u03b22\/3 promoter DNA methylation and Smad signaling during palatal fusion induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin","volume":"246","author":"Chen","year":"2021","journal-title":"Exp. Biol. Med. (Maywood)"},{"key":"B31","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1093\/toxres\/tfac068","article-title":"TCDD induces cleft palate through exosomes derived from mesenchymal cells","volume":"11","author":"Chen","year":"2022","journal-title":"Toxicol. Res. (Camb.)"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2455","DOI":"10.1002\/tox.22459","article-title":"Actein alleviates 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated cellular dysfunction in osteoblastic MC3T3-E1 cells","volume":"32","author":"Choi","year":"2017","journal-title":"Environ. Toxicol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"122499","DOI":"10.1016\/j.envpol.2023.122499","article-title":"Exposure to the aryl hydrocarbon receptor agonist dioxin disrupts formation of the muscle, nerves, and vasculature in the developing jaw","volume":"337","author":"Cintr\u00f3n-Rivera","year":"2023","journal-title":"Environ. Pollut."},{"key":"B34","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1002\/tera.1420420606","article-title":"A critical review of the developmental toxicity and teratogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin: recent advances toward understanding the mechanism","volume":"42","author":"Couture","year":"1990","journal-title":"Teratology"},{"key":"B35","doi-asserted-by":"publisher","first-page":"2484","DOI":"10.1016\/j.talanta.2011.07.103","article-title":"Quantification of PCDD\/Fs and dioxin-like PCBs in small amounts of human serum using the sensitive H1L7.5c1 mouse hepatoma cell line: optimization and analysis of human serum samples from adolescents of the Flemish human biomonitoring program FLEHS II","volume":"85","author":"Croes","year":"2011","journal-title":"Talanta"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1021\/es2022363","article-title":"Human exposure from dioxins in soil","volume":"46","author":"Demond","year":"2012","journal-title":"Environ. Sci. Technol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1146\/annurev.pharmtox.43.100901.135828","article-title":"Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals","volume":"43","author":"Denison","year":"2003","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1093\/carcin\/22.1.171","article-title":"Aryl hydrocarbon receptor signaling plays a significant role in mediating benzo[a]pyrene- and cigarette smoke condensate-induced cytogenetic damage in vivo","volume":"22","author":"Dertinger","year":"2001","journal-title":"Carcinogenesis"},{"key":"B39","doi-asserted-by":"publisher","first-page":"105525","DOI":"10.1016\/j.yrtph.2023.105525","article-title":"The 2022 World Health Organization reevaluation of human and mammalian toxic equivalency factors for polychlorinated dioxins, dibenzofurans and biphenyls","volume":"146","author":"DeVito","year":"2024","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1007\/s12011-018-1580-y","article-title":"The protective effect of \u03b1-tocopherol on the content of selected elements in the calvaria for exposed hens to TCDD in the early embryonic period","volume":"190","author":"Dobrzynski","year":"2019","journal-title":"Biol. Trace Elem. Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"484","DOI":"10.3390\/ani12040484","article-title":"Assessment of selected morphological, physical and chemical parameters of the teeth of the offspring of female rats exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), taking into account the protective role of selected antioxidants-preliminary study","volume":"12","author":"Dobrzy\u0144ski","year":"2022","journal-title":"Anim. (Basel)"},{"key":"B42","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1093\/bmb\/ldg024","article-title":"The impact of environmental pollution on congenital anomalies","volume":"68","author":"Dolk","year":"2003","journal-title":"Br. Med. Bull."},{"key":"B43","doi-asserted-by":"publisher","first-page":"10556656241286314","DOI":"10.1177\/10556656241286314","article-title":"2,3,7,8-Tetrachlorodibenzo-p-dioxin suppresses mesenchymal cell proliferation and migration through miR-214-3p in cleft palate","volume":"62","author":"Dong","year":"2024","journal-title":"Cleft Palate Craniofac. J."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1080\/10962247.2015.1058869","article-title":"Review of the current state and main sources of dioxins around the world","volume":"65","author":"Dopico","year":"2015","journal-title":"J. Air Waste Manag. Assoc."},{"key":"B45","doi-asserted-by":"publisher","first-page":"18591","DOI":"10.1074\/jbc.M601159200","article-title":"For dioxin-induced birth defects, mouse or human CYP1A2 in maternal liver protects whereas mouse CYP1A1 and CYP1B1 are inconsequential","volume":"281","author":"Dragin","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1823615","DOI":"10.3389\/fphar.2026.1823615","article-title":"The landscape of biased agonism in aryl hydrocarbon receptor signaling: current clues and future directions","volume":"17","author":"Dvo\u0159\u00e1k","year":"2026","journal-title":"Front. Pharmacol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1741-4520.2003.tb01022.x","article-title":"The interplay of genetic and environmental factors in craniofacial morphogenesis: holoprosencephaly and the role of cholesterol","volume":"43","author":"Edison","year":"2003","journal-title":"Congenit. Anom. (Kyoto)"},{"key":"B48","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1177\/0192623312457270","article-title":"Comparison of destructive periodontal disease in blue iris mink to PCB 126-induced mandibular and maxillary squamous epithelial proliferation in natural dark mink","volume":"41","author":"Ellick","year":"2013","journal-title":"Toxicol. Pathol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1038\/ijos.2017.17","article-title":"The oral commensal Streptococcus mitis activates the aryl hydrocarbon receptor in human oral epithelial cells","volume":"9","author":"Engen","year":"2017","journal-title":"Int. J. Oral Sci."},{"key":"B50","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1289\/ehp.1306788","article-title":"Serum dioxin concentrations and bone density and structure in the Seveso Women\u2019s Health Study","volume":"122","author":"Eskenazi","year":"2014","journal-title":"Environ. Health Perspect."},{"key":"B51","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.envint.2018.08.051","article-title":"The Seveso accident: a look at 40 years of health research and beyond","volume":"121","author":"Eskenazi","year":"2018","journal-title":"Environ. Int."},{"key":"B52","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1093\/humrep\/deaa324","article-title":"Dioxin exposure associated with fecundability and infertility in mothers and daughters of Seveso, Italy","volume":"36","author":"Eskenazi","year":"2021","journal-title":"Hum. Reprod."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1177\/10556656211040015","article-title":"Maternal cigarette smoking and cleft lip and palate: a systematic review and meta-analysis","volume":"59","author":"Fell","year":"2022","journal-title":"Cleft Palate Craniofac. J."},{"key":"B54","doi-asserted-by":"publisher","first-page":"143191","DOI":"10.1016\/j.scitotenv.2020.143191","article-title":"Polybrominated dibenzo-p-dioxins and furans (PBDD\/Fs): contamination in food, humans and dietary exposure","volume":"761","author":"Fernandes","year":"2021","journal-title":"Sci. Total Environ."},{"key":"B55","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1126\/science.7732381","article-title":"Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor","volume":"268","author":"Fernandez-Salguero","year":"1995","journal-title":"Science"},{"key":"B56","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1006\/taap.1996.0210","article-title":"Aryl-hydrocarbon receptor-deficient mice are resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxicity","volume":"140","author":"Fernandez-Salguero","year":"1996","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1080\/02772249009357628","article-title":"Dioxins: sources of environmental load and human exposure","volume":"29","author":"Fiedler","year":"1990","journal-title":"Toxicol. and Environ. Chem."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1016\/j.jbiomech.2009.12.011","article-title":"Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on bone material properties","volume":"43","author":"Finnil\u00e4","year":"2010","journal-title":"J. Biomech."},{"key":"B59","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.ijheh.2014.07.004","article-title":"PCBs, PCDD\/Fs, and PBDEs in blood samples of a rural population in south Germany","volume":"218","author":"Fromme","year":"2015","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"B60","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1111\/j.1741-4520.2008.00181.x","article-title":"Morphological and immunohistochemical studies on cleft palates induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice","volume":"48","author":"Fujiwara","year":"2008","journal-title":"Congenit. Anom. (Kyoto)"},{"key":"B61","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1177\/0748233709345940","article-title":"Transforming growth factor-beta3 expression up-regulates on cleft palates induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice","volume":"25","author":"Gan","year":"2009","journal-title":"Toxicol. Ind. Health"},{"key":"B62","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1177\/154405910408300211","article-title":"Lactational exposure of Han\/Wistar rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin interferes with enamel maturation and retards dentin mineralization","volume":"83","author":"Gao","year":"2004","journal-title":"J. Dent. Res."},{"key":"B63","doi-asserted-by":"publisher","first-page":"676","DOI":"10.3967\/bes2017.090","article-title":"LncRNA H19 and target gene-mediated cleft palate induced by TCDD","volume":"30","author":"Gao","year":"2017","journal-title":"Biomed. Environ. Sci."},{"key":"B64","doi-asserted-by":"publisher","first-page":"1559325818786822","DOI":"10.1177\/1559325818786822","article-title":"2,3,7,8-Tetrachlorodibenzo-p-dioxin and TGF\u03b23-mediated mouse embryonic palatal mesenchymal cells","volume":"17","author":"Gao","year":"2019","journal-title":"Dose Response"},{"key":"B65","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1177\/0960327119899996","article-title":"Identification and characterization of differentially expressed lncRNA in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cleft palate","volume":"39","author":"Gao","year":"2020","journal-title":"Hum. Exp. Toxicol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"9603271231183359","DOI":"10.1177\/09603271231183359","article-title":"Identification and characterization of differentially expressed circRNA in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cleft palate","volume":"42","author":"Gao","year":"2023","journal-title":"Hum. Exp. Toxicol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"e0193484","DOI":"10.1371\/journal.pone.0193484","article-title":"AHR2 required for normal behavioral responses and proper development of the skeletal and reproductive systems in zebrafish","volume":"13","author":"Garcia","year":"2018","journal-title":"PLoS One"},{"key":"B68","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1093\/toxsci\/kfn154","article-title":"PCB126 exposure disrupts zebrafish ventricular and branchial but not early neural crest development","volume":"106","author":"Grimes","year":"2008","journal-title":"Toxicol. Sci."},{"key":"B69","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1016\/j.envint.2018.10.028","article-title":"Dioxins as potential risk factors for autism spectrum disorder","volume":"121","author":"Guo","year":"2018","journal-title":"Environ. Int."},{"key":"B70","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1007\/bf00316581","article-title":"Teratological studies on the TCDD congener 3,3',4,4'-tetrachloroazoxybenzene in sensitive and nonsensitive mouse strains: evidence for direct effect on embryonic tissues","volume":"55","author":"Hassoun","year":"1984","journal-title":"Arch. Toxicol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/s0300-483x(97)00127-3","article-title":"Modulation of TCDD-induced fetotoxicity and oxidative stress in embryonic and placental tissues of C57BL\/6J mice by vitamin E succinate and ellagic acid","volume":"124","author":"Hassoun","year":"1997","journal-title":"Toxicology"},{"key":"B72","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/s0273-2300(02)00044-2","article-title":"Dioxin risks in perspective: past, present, and future","volume":"37","author":"Hays","year":"2003","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"115517","DOI":"10.1016\/j.taap.2021.115517","article-title":"The role of MEG3 in the proliferation of palatal mesenchymal cells is related to the TGF\u03b2\/Smad pathway in TCDD inducing cleft palate","volume":"419","author":"He","year":"2021","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.tox.2010.04.006","article-title":"Quantitative characterization of changes in bone geometry, mineral density and biomechanical properties in two rat strains with different Ah-receptor structures after long-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin","volume":"273","author":"Herlin","year":"2010","journal-title":"Toxicology"},{"key":"B75","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.reprotox.2021.07.013","article-title":"Bone toxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the retinoid system: a causality analysis anchored in osteoblast gene expression and mouse data","volume":"105","author":"Herlin","year":"2021","journal-title":"Reprod. Toxicol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1093\/toxsci\/47.1.40","article-title":"2,3,7,8-Tetrachlorodibenzo-p-dioxin alters cardiovascular and craniofacial development and function in sac fry of rainbow trout (Oncorhynchus mykiss)","volume":"47","author":"Hornung","year":"1999","journal-title":"Toxicol. Sci."},{"key":"B77","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1597\/13-018","article-title":"2,3,7,8-Tetrachlorodibenzo-p-dioxin delays palatal shelf elevation and suppresses Wnt5a and lymphoid enhancing-binding factor 1 signaling in developing palate","volume":"52","author":"Hu","year":"2015","journal-title":"Cleft Palate Craniofac. J."},{"key":"B78","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1006\/taap.1994.1021","article-title":"Developmental toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the most TCDD-resistant and -susceptible rat strains","volume":"124","author":"Huuskonen","year":"1994","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.lfs.2013.07.020","article-title":"Bisphenol A reduces differentiation and stimulates apoptosis of osteoclasts and osteoblasts","volume":"93","author":"Hwang","year":"2013","journal-title":"Life Sci."},{"key":"B80","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1111\/j.1741-4520.2010.00271.x","article-title":"Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin suggests abnormal palate development after palatal fusion","volume":"50","author":"Imura","year":"2010","journal-title":"Congenit. Anom. (Kyoto)"},{"key":"B81","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1248\/bpb.27.1397","article-title":"Reduction of the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice using an antiulcer drug, geranylgeranylacetone","volume":"27","author":"Ishida","year":"2004","journal-title":"Biol. Pharm. Bull."},{"key":"B82","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1111\/j.1601-0825.2011.01806.x","article-title":"The mechanism of TGF-\u03b2 signaling during palate development","volume":"17","author":"Iwata","year":"2011","journal-title":"Oral Dis."},{"key":"B83","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1289\/ehp.1003075","article-title":"Retinoic acid drives aryl hydrocarbon receptor expression and is instrumental to dioxin-induced toxicity during palate development","volume":"119","author":"Jacobs","year":"2011","journal-title":"Environ. Health Perspect."},{"key":"B84","doi-asserted-by":"publisher","first-page":"e534","DOI":"10.1097\/scs.0000000000004488","article-title":"Maternal folic acid supplementation and the risk of oral clefts in offspring","volume":"29","author":"Jahanbin","year":"2018","journal-title":"J. Craniofac. Surg."},{"key":"B85","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.reprotox.2007.08.002","article-title":"Antiteratogenic effects of alpha-naphthoflavone on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposed mice in utero","volume":"24","author":"Jang","year":"2007","journal-title":"Reprod. Toxicol."},{"key":"B86","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.ejphar.2008.05.033","article-title":"Antiteratogenic effect of resveratrol in mice exposed in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin","volume":"591","author":"Jang","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1093\/toxsci\/kfp116","article-title":"Distinct roles of two zebrafish AHR repressors (AHRRa and AHRRb) in embryonic development and regulating the response to 2,3,7,8-tetrachlorodibenzo-p-dioxin","volume":"110","author":"Jenny","year":"2009","journal-title":"Toxicol. Sci."},{"key":"B88","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1177\/154405910508400801","article-title":"Epithelial-mesenchymal transformation during craniofacial development","volume":"84","author":"Kang","year":"2005","journal-title":"J. Dent. Res."},{"key":"B89","doi-asserted-by":"publisher","first-page":"7143","DOI":"10.1158\/0008-5472.Can-05-4541","article-title":"High levels of dioxin-like potential in cigarette smoke evidenced by in vitro and in vivo biosensing","volume":"66","author":"Kasai","year":"2006","journal-title":"Cancer Res."},{"key":"B90","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1006\/taap.2001.9216","article-title":"In utero\/lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure impairs molar tooth development in rats","volume":"174","author":"Kattainen","year":"2001","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B91","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1002\/ajmg.a.30023","article-title":"Significant association between nonsyndromic oral clefts and arylhydrocarbon receptor nuclear translocator (ARNT)","volume":"130","author":"Kayano","year":"2004","journal-title":"Am. J. Med. Genet. A."},{"key":"B92","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.archoralbio.2006.10.017","article-title":"Qualitative effects of dioxin on molars vary among inbred mouse strains","volume":"52","author":"Keller","year":"2007","journal-title":"Arch. Oral Biol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1177\/0192623308327409","article-title":"Genetic differences in sensitivity to alterations of mandible structure caused by the teratogen 2,3,7,8-tetrachlorodibenzo-p-dioxin","volume":"36","author":"Keller","year":"2008","journal-title":"Toxicol. Pathol."},{"key":"B94","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1289\/ehp.8884","article-title":"Age- and concentration-dependent elimination half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Seveso children","volume":"114","author":"Kerger","year":"2006","journal-title":"Environ. Health Perspect."},{"key":"B95","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.canlet.2006.11.015","article-title":"Cigarette smoke as a trigger for the dioxin receptor-mediated signaling pathway","volume":"252","author":"Kitamura","year":"2007","journal-title":"Cancer Lett."},{"key":"B96","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1093\/toxsci\/69.2.482","article-title":"Response of the incisor tooth to 2,3,7,8-tetrachlorodibenzo-p-dioxin in a dioxin-resistant and a dioxin-sensitive rat strain","volume":"69","author":"Kiukkonen","year":"2002","journal-title":"Toxicol. Sci."},{"key":"B97","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1093\/humupd\/7.3.331","article-title":"Human health effects of dioxins: cancer, reproductive and endocrine system effects","volume":"7","author":"Kogevinas","year":"2001","journal-title":"Hum. Reprod. Update"},{"key":"B98","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1016\/0045-6535(90)90241-k","article-title":"Comparison of cleft palate frequency and TCDD concentration in mice at different stages of development","volume":"20","author":"Krowke","year":"1990","journal-title":"Chemosphere"},{"key":"B99","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.envint.2007.07.009","article-title":"Dioxins sources and current remediation technologies\u2013a review","volume":"34","author":"Kulkarni","year":"2008","journal-title":"Environ. Int."},{"key":"B101","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1177\/0960327119855121","article-title":"Can contamination of the environment by dioxins cause craniofacial defects?","volume":"38","author":"Le\u015bk\u00f3w","year":"2019","journal-title":"Hum. Exp. Toxicol."},{"key":"B102","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1177\/0748233710364964","article-title":"Is it possible to antagonize 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin- induced cleft palate by prenatal administration of folic acid? An experimental study","volume":"26","author":"Li","year":"2010","journal-title":"Toxicol. Ind. Health"},{"key":"B103","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1177\/0022034517703580","article-title":"Molecular and cellular mechanisms of palate development","volume":"96","author":"Li","year":"2017","journal-title":"J. Dent. Res."},{"key":"B104","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1186\/s12903-019-0935-x","article-title":"1,25-dihydroxyvitamin D3 suppresses lipopolysaccharide-induced interleukin-6 production through aryl hydrocarbon receptor\/nuclear factor-\u03baB signaling in oral epithelial cells","volume":"19","author":"Li","year":"2019","journal-title":"BMC Oral Health"},{"key":"B105","doi-asserted-by":"publisher","first-page":"105984","DOI":"10.1016\/j.envint.2020.105984","article-title":"Serum metabolic changes associated with dioxin exposure in a Chinese male cohort","volume":"143","author":"Liang","year":"2020","journal-title":"Environ. Int."},{"key":"B106","doi-asserted-by":"publisher","first-page":"108319","DOI":"10.1016\/j.mrrev.2020.108319","article-title":"A comprehensive analysis of AHRR gene as a candidate for cleft lip with or without cleft palate","volume":"785","author":"Linnenkamp","year":"2020","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"B107","doi-asserted-by":"publisher","first-page":"152353","DOI":"10.1016\/j.tox.2019.152353","article-title":"TCDD inhibited the osteogenic differentiation of human fetal palatal mesenchymal cells through AhR and BMP-2\/TGF-\u03b2\/Smad signaling","volume":"431","author":"Liu","year":"2020","journal-title":"Toxicology"},{"key":"B108","doi-asserted-by":"publisher","first-page":"114410","DOI":"10.1016\/j.fct.2023.114410","article-title":"Upregulated lncRNA-Meg3 modulates the proliferation and survival of MEPM cells via interacting with Smad signaling in TCDD-induced cleft palate","volume":"185","author":"Liu","year":"2024","journal-title":"Food Chem. Toxicol."},{"key":"B109","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1006\/taap.2001.9155","article-title":"Arrest of rat molar tooth development by lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin","volume":"173","author":"Lukinmaa","year":"2001","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B110","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s00360-005-0483-3","article-title":"Dioxin: a review of its environmental effects and its aryl hydrocarbon receptor biology","volume":"175","author":"Mandal","year":"2005","journal-title":"J. Comp. Physiol. B"},{"key":"B111","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1002\/etc.4329","article-title":"Induction of maxillary and mandibular squamous epithelial cell proliferation in mink (Neovison vison) by \u03b2-naphthoflavone","volume":"38","author":"Matz","year":"2019","journal-title":"Environ. Toxicol. Chem."},{"key":"B112","doi-asserted-by":"publisher","first-page":"e22","DOI":"10.1017\/s2040174424000229","article-title":"Juvenile exposure to low-level 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters behavior and longitudinal morphometrics in zebrafish and F1 offspring","volume":"15","author":"Meyer","year":"2024","journal-title":"J. Dev. Orig. Health Dis."},{"key":"B113","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1006\/taap.2002.9490","article-title":"Effect of in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on rat molar development: the role of exposure time","volume":"184","author":"Miettinen","year":"2002","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B114","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1093\/toxsci\/kfj158","article-title":"The effect of perinatal TCDD exposure on caries susceptibility in rats","volume":"91","author":"Miettinen","year":"2006","journal-title":"Toxicol. Sci."},{"key":"B115","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1289\/ehp.8560211","article-title":"Congenital PCB poisoning: a reevaluation","volume":"60","author":"Miller","year":"1985","journal-title":"Environ. Health Perspect."},{"key":"B116","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1046\/j.1365-2443.1997.1490345.x","article-title":"Loss of teratogenic response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice lacking the Ah (dioxin) receptor","volume":"2","author":"Mimura","year":"1997","journal-title":"Genes Cells."},{"key":"B117","doi-asserted-by":"publisher","first-page":"5652","DOI":"10.1073\/pnas.1037886100","article-title":"Distinct response to dioxin in an arylhydrocarbon receptor (AHR)-humanized mouse","volume":"100","author":"Moriguchi","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B118","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1016\/s0140-6736(09)60695-4","article-title":"Cleft lip and palate","volume":"374","author":"Mossey","year":"2009","journal-title":"Lancet"},{"key":"B119","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1080\/00039896.1989.9935882","article-title":"Dioxins in cigarette smoke","volume":"44","author":"Muto","year":"1989","journal-title":"Arch. Environ. Health"},{"key":"B120","doi-asserted-by":"publisher","first-page":"111971","DOI":"10.1016\/j.ecoenv.2021.111971","article-title":"Evaluation of the dioxin-like toxicity in soil samples from Thua Thien Hue province using the AhR-CALUX bioassay - an update of Agent Orange contamination in Vietnam","volume":"212","author":"My","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"B121","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/0300-483x(81)90037-8","article-title":"Transfer of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to the mouse embryo and fetus","volume":"20","author":"Nau","year":"1981","journal-title":"Toxicology"},{"key":"B122","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.taap.2009.01.025","article-title":"Dioxin-induced up-regulation of the active form of vitamin D is the main cause for its inhibitory action on osteoblast activities, leading to developmental bone toxicity","volume":"236","author":"Nishimura","year":"2009","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B123","doi-asserted-by":"publisher","first-page":"82169","DOI":"10.1007\/s11356-022-21611-1","article-title":"Investigation of exposure to heavy metals (Hg, Pb, Cd, Co, and Cr) as the cause of congenital anomaly cases (orofacial cleft) in infants","volume":"29","author":"Oginawati","year":"2022","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"B124","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/nature05683","article-title":"Dioxin receptor is a ligand-dependent E3 ubiquitin ligase","volume":"446","author":"Ohtake","year":"2007","journal-title":"Nature"},{"key":"B125","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1016\/s0890-6238(97)00068-3","article-title":"Retinoic acid-induced asymmetric craniofacial growth and cleft palate in the TO mouse fetus","volume":"11","author":"Padmanabhan","year":"1997","journal-title":"Reprod. Toxicol."},{"key":"B126","doi-asserted-by":"publisher","first-page":"351","DOI":"10.22074\/ijfs.2015.4174","article-title":"Association between environmental dioxin-related toxicants exposure and adverse pregnancy outcome: systematic review and meta-analysis","volume":"8","author":"Pan","year":"2015","journal-title":"Int. J. Fertil. Steril."},{"key":"B127","first-page":"1473","article-title":"Epidermal growth factor receptor as a mediator of developmental toxicity of dioxin in mouse embryonic teeth","volume":"78","author":"Partanen","year":"1998","journal-title":"Lab. Invest."},{"key":"B128","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.taap.2003.08.014","article-title":"Developmental toxicity of dioxin to mouse embryonic teeth in vitro: arrest of tooth morphogenesis involves stimulation of apoptotic program in the dental epithelium","volume":"194","author":"Partanen","year":"2004","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B129","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1002\/jcb.24417","article-title":"Identification of candidate downstream targets of TGF\u03b2 signaling during palate development by genome-wide transcript profiling","volume":"114","author":"Pelikan","year":"2013","journal-title":"J. Cell Biochem."},{"key":"B130","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1093\/toxsci\/47.1.86","article-title":"Amelioration of TCDD-induced teratogenesis in aryl hydrocarbon receptor (AhR)-null mice","volume":"47","author":"Peters","year":"1999","journal-title":"Toxicol. Sci."},{"key":"B131","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1021\/tx9003165","article-title":"2,3,7,8-Tetrachlorodibenzo-p-dioxin upregulates FoxQ1b in zebrafish jaw primordium","volume":"23","author":"Planchart","year":"2010","journal-title":"Chem. Res. Toxicol."},{"key":"B132","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.bcp.2004.06.043","article-title":"Ah receptor signals cross-talk with multiple developmental pathways","volume":"69","author":"Puga","year":"2005","journal-title":"Biochem. Pharmacol."},{"key":"B133","doi-asserted-by":"publisher","first-page":"152772","DOI":"10.1016\/j.tox.2021.152772","article-title":"Susceptibility to DNA damage caused by abrogation of Rad54 homolog B: a putative mechanism for chemically induced cleft palate","volume":"456","author":"Qiao","year":"2021","journal-title":"Toxicology"},{"key":"B134","doi-asserted-by":"publisher","first-page":"dmm037051","DOI":"10.1242\/dmm.037051","article-title":"Wnt signaling in orofacial clefts: crosstalk, pathogenesis and models","volume":"12","author":"Reynolds","year":"2019","journal-title":"Dis. Model. Mech."},{"key":"B135","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1126\/science.3133768","article-title":"Congenital poisoning by polychlorinated biphenyls and their contaminants in Taiwan","volume":"241","author":"Rogan","year":"1988","journal-title":"Science"},{"key":"B136","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1023\/a:1009550912337","article-title":"Mechanisms of inhibitory aryl hydrocarbon receptor-estrogen receptor crosstalk in human breast cancer cells","volume":"5","author":"Safe","year":"2000","journal-title":"J. Mammary Gland. Biol. Neoplasia"},{"key":"B137","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1387\/ijdb.12068950","article-title":"Expression of the mediators of dioxin toxicity, aryl hydrocarbon receptor (AHR) and the AHR nuclear translocator (ARNT), is developmentally regulated in mouse teeth","volume":"46","author":"Sahlberg","year":"2002","journal-title":"Int. J. Dev. Biol."},{"key":"B138","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1016\/j.jcms.2018.09.016","article-title":"Cleft palate formation after palatal fusion occurs due to the rupture of epithelial basement membranes","volume":"46","author":"Sakuma","year":"2018","journal-title":"J. Craniomaxillofac. Surg."},{"key":"B139","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.3390\/ijms23042069","article-title":"Histological and immunohistochemical studies to determine the mechanism of cleft palate induction after palatal fusion in mice exposed to TCDD","volume":"23","author":"Sakuma","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B140","doi-asserted-by":"publisher","first-page":"2448","DOI":"10.3390\/nu14122448","article-title":"Quercetin reduces the development of 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced cleft palate in mice by suppressing CYP1A1 via the aryl hydrocarbon receptor","volume":"14","author":"Satake","year":"2022","journal-title":"Nutrients"},{"key":"B141","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-0-387-36903-7_1","article-title":"Dioxin formation from waste incineration","volume":"190","author":"Shibamoto","year":"2007","journal-title":"Rev. Environ. Contam. Toxicol."},{"key":"B142","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.toxrep.2014.12.007","article-title":"Craniofacial form is altered by chronic adult exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Han\/Wistar and Long-Evans rats with different aryl hydrocarbon receptor (AhR) structures","volume":"2","author":"Sholts","year":"","journal-title":"Toxicol. Rep."},{"key":"B143","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.tox.2015.08.010","article-title":"In utero\/lactational and adult exposures to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) show differential effects on craniofacial development and growth in rats","volume":"337","author":"Sholts","year":"","journal-title":"Toxicology"},{"key":"B144","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1124\/mol.106.028365","article-title":"Role of dioxin response element and nuclear factor-kappaB motifs in 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated regulation of Fas and Fas ligand expression","volume":"71","author":"Singh","year":"2007","journal-title":"Mol. Pharmacol."},{"key":"B145","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1016\/s0045-6535(99)00337-9","article-title":"Degradation half-life times of PCDDs, PCDFs and PCBs for environmental fate modeling","volume":"40","author":"Sinkkonen","year":"2000","journal-title":"Chemosphere"},{"key":"B146","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1177\/0748233708089042","article-title":"Early life-stage toxicity in zebrafish (Danio rerio) following embryonal exposure to selected polychlorinated biphenyls","volume":"23","author":"Si\u015fman","year":"2007","journal-title":"Toxicol. Ind. Health"},{"key":"B147","doi-asserted-by":"publisher","first-page":"136615","DOI":"10.1016\/j.jhazmat.2024.136615","article-title":"Dioxin-like polychlorinated biphenyls (dl-PCB) in hydrochars and biochars: review of recent evidence, pollution levels, critical gaps, formation mechanisms and regulations","volume":"486","author":"Sobol","year":"2024","journal-title":"J. Hazard. Mat."},{"key":"B148","doi-asserted-by":"publisher","first-page":"3549","DOI":"10.1007\/s00204-018-2320-y","article-title":"Head skeleton malformations in zebrafish (Danio rerio) to assess adverse effects of mixtures of compounds","volume":"92","author":"Staal","year":"2018","journal-title":"Arch. Toxicol."},{"key":"B149","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1038\/s41415-023-6463-8","article-title":"Craniofacial development","volume":"235","author":"Stimson","year":"2023","journal-title":"Br. Dent. J."},{"key":"B150","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1080\/10934529.2018.1428275","article-title":"27-Deoxyactein prevents 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cellular damage in MC3T3-E1 osteoblastic cells","volume":"53","author":"Suh","year":"2018","journal-title":"J. Environ. Sci. Health A Tox. Hazard. Subst. Environ. Eng."},{"key":"B151","doi-asserted-by":"publisher","first-page":"640","DOI":"10.3389\/fcell.2020.00640","article-title":"Formation and developmental specification of the odontogenic and osteogenic mesenchymes","volume":"8","author":"Svandova","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"B152","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.jpeds.2016.04.064","article-title":"Effects of perinatal dioxin exposure on development of children during the first 3 years of life","volume":"175","author":"Tai","year":"2016","journal-title":"J. Pediatr."},{"key":"B153","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/(sici)1520-6866(2000)20:2<73::aid-tcm3>3.0.co;2-m","article-title":"Pathogenesis of cleft palate in mouse embryos exposed to 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD)","volume":"20","author":"Takagi","year":"2000","journal-title":"Teratog. Carcinog. Mutagen."},{"key":"B154","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3390\/toxics11010007","article-title":"Effects of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and dioxin-like PCBs on teeth and bones in animals and humans","volume":"11","author":"Takiguchi","year":"2022","journal-title":"Toxics"},{"key":"B155","doi-asserted-by":"publisher","first-page":"152444","DOI":"10.1016\/j.tox.2020.152444","article-title":"Oct4 plays a role in 2, 3, 7, 8 - tetrachlorobenzo-p-dioxin (TCDD) inducing cleft palate and inhibiting mesenchymal proliferation","volume":"438","author":"Tao","year":"2020","journal-title":"Toxicology"},{"key":"B156","doi-asserted-by":"publisher","first-page":"30189","DOI":"10.1074\/jbc.M403690200","article-title":"A maternal Ahr null genotype sensitizes embryos to chemical teratogenesis","volume":"279","author":"Thomae","year":"2004","journal-title":"J. Biol. Chem."},{"key":"B157","doi-asserted-by":"publisher","first-page":"12742","DOI":"10.1074\/jbc.M410780200","article-title":"Transforming growth factor-beta3 restores fusion in palatal shelves exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin","volume":"280","author":"Thomae","year":"2005","journal-title":"J. Biol. Chem."},{"key":"B158","doi-asserted-by":"publisher","first-page":"3093","DOI":"10.1002\/jcb.24186","article-title":"Alternation of extracellular matrix remodeling and apoptosis by activation of the aryl hydrocarbon receptor pathway in human periodontal ligament cells","volume":"113","author":"Tomokiyo","year":"2012","journal-title":"J. Cell Biochem."},{"key":"B159","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/0048-9697(91)90010-c","article-title":"Human exposure to dioxin","volume":"104","author":"Travis","year":"1991","journal-title":"Sci. Total Environ."},{"key":"B160","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1289\/ehp.0800012","article-title":"Prevalence of metabolic syndrome associated with body burden levels of dioxin and related compounds among Japan's general population","volume":"117","author":"Uemura","year":"2009","journal-title":"Environ. Health Perspect."},{"key":"B161","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3109\/10408449409017919","article-title":"The toxicokinetics and metabolism of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and their relevance for toxicity","volume":"24","author":"Van den Berg","year":"1994","journal-title":"Crit. Rev. Toxicol."},{"key":"B162","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1289\/ehp.98106775","article-title":"Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife","volume":"106","author":"Van den Berg","year":"1998","journal-title":"Environ. Health Perspect."},{"key":"B163","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1093\/toxsci\/kfl055","article-title":"The 2005 World Health Organization reevaluation of human and mammalian toxic equivalency factors for dioxins and dioxin-like compounds","volume":"93","author":"Van den Berg","year":"2006","journal-title":"Toxicol. Sci."},{"key":"B164","doi-asserted-by":"publisher","first-page":"14431","DOI":"10.1007\/s11356-014-3946-9","article-title":"Transport and bioaccumulation of polychlorinated dibenzo-p-dioxins and dibenzofurans at the Bien Hoa Agent Orange hotspot in Vietnam","volume":"22","author":"Van Thuong","year":"2015","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"B165","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1016\/j.jcms.2017.02.004","article-title":"Preliminary research on DNA methylation changes during murine palatogenesis induced by TCDD","volume":"45","author":"Wang","year":"2017","journal-title":"J. Craniomaxillofac. Surg."},{"key":"B166","doi-asserted-by":"publisher","first-page":"103270","DOI":"10.1016\/j.etap.2019.103270","article-title":"Common differentially expressed proteins were found in mouse cleft palate models induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin and retinoic acid","volume":"72","author":"Wang","year":"2019","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"B167","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1177\/0960327120937342","article-title":"IL-12p40 and sRAGE in serum correlate with chemically induced cleft palate in mice","volume":"39","author":"Wang","year":"2020","journal-title":"Hum. Exp. Toxicol."},{"key":"B168","doi-asserted-by":"publisher","first-page":"117743","DOI":"10.1016\/j.ecoenv.2025.117743","article-title":"Comprehensive three-dimensional microCT and signaling analysis reveal the teratogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on craniofacial bone development in mice","volume":"290","author":"Wang","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"B169","doi-asserted-by":"publisher","first-page":"105286","DOI":"10.1016\/j.envint.2019.105286","article-title":"Prenatal dioxin exposure and glucose metabolism in the Seveso Second Generation Study","volume":"134","author":"Warner","year":"2020","journal-title":"Environ. Int."},{"key":"B170","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1093\/toxsci\/kfy225","article-title":"Evidence for aryl hydrocarbon receptor-mediated inhibition of osteoblast differentiation in human mesenchymal stem cells","volume":"167","author":"Watson","year":"2019","journal-title":"Toxicol. Sci."},{"key":"B171","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/bf00290880","article-title":"2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and 2,3,7,8-tetrachlorodibenzofuran (TCDF) in pregnant C57BL\/6N mice: distribution to the embryo and excretion","volume":"57","author":"Weber","year":"1985","journal-title":"Arch. Toxicol."},{"key":"B172","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1007\/s11356-008-0024-1","article-title":"Dioxin- and POP-contaminated sites\u2013contemporary and future relevance and challenges: overview on background, aims and scope of the series","volume":"15","author":"Weber","year":"","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"B173","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1065\/espr2008.01.473","article-title":"Dioxin\u2013contemporary and future challenges of historical legacies. Dedicated to Prof. Dr. Otto Hutzinger, the founder of the DIOXIN Conference Series","volume":"15","author":"Weber","year":"","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"B174","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1093\/toxsci\/kfp284","article-title":"Transgenic mice with a constitutively active aryl hydrocarbon receptor display a gender-specific bone phenotype","volume":"114","author":"Wejheden","year":"2010","journal-title":"Toxicol. Sci."},{"key":"B175","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.envint.2013.11.005","article-title":"Maternal dioxin exposure and pregnancy outcomes over 30 years of follow-up in Seveso","volume":"63","author":"Wesselink","year":"2014","journal-title":"Environ. Int."},{"key":"B176","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1006\/bbrc.1995.1242","article-title":"Inhibition of retinoic-acid-induced gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin","volume":"207","author":"Weston","year":"1995","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B177","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1016\/j.fct.2008.01.009","article-title":"Assessment of dioxin and dioxin-like compounds in mainstream smoke from selected US cigarette brands and reference cigarettes","volume":"46","author":"Wilson","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"B178","doi-asserted-by":"publisher","first-page":"1954","DOI":"10.3390\/cells12151954","article-title":"Gene regulatory networks and signaling pathways in palatogenesis and cleft palate: a comprehensive review","volume":"12","author":"Won","year":"2023","journal-title":"Cells"},{"key":"B179","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1124\/mol.108.050435","article-title":"Aryl hydrocarbon receptor-mediated down-regulation of sox9b causes jaw malformation in zebrafish embryos","volume":"74","author":"Xiong","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"B180","doi-asserted-by":"publisher","first-page":"38012","DOI":"10.1038\/srep38012","article-title":"Association between dioxin and cancer incidence and mortality: a meta-analysis","volume":"6","author":"Xu","year":"2016","journal-title":"Sci. Rep."},{"key":"B181","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1097\/scs.0000000000004214","article-title":"A study on environmental factors for nonsyndromic cleft lip and\/or palate","volume":"29","author":"Xu","year":"","journal-title":"J. Craniofac. Surg."},{"key":"B182","doi-asserted-by":"publisher","first-page":"dev165498","DOI":"10.1242\/dev.165498","article-title":"Fox proteins are modular competency factors for facial cartilage and tooth specification","volume":"145","author":"Xu","year":"","journal-title":"Development"},{"key":"B183","doi-asserted-by":"publisher","first-page":"e63595","DOI":"10.7554\/eLife.63595","article-title":"Foxc1 establishes enhancer accessibility for craniofacial cartilage differentiation","volume":"10","author":"Xu","year":"2021","journal-title":"Elife"},{"key":"B184","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1053\/j.gastro.2016.09.064","article-title":"Aryl hydrocarbon receptor ligands in cigarette smoke induce production of interleukin-22 to promote pancreatic fibrosis in models of chronic pancreatitis","volume":"151","author":"Xue","year":"2016","journal-title":"Gastroenterology"},{"key":"B185","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1111\/j.1741-4520.2006.00097.x","article-title":"Cleft lip and palate in mice treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin: a morphological in vivo study","volume":"46","author":"Yamada","year":"2006","journal-title":"Congenit. Anom. (Kyoto)"},{"key":"B186","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jcms.2013.01.024","article-title":"TCDD disrupts posterior palatogenesis and causes cleft palate","volume":"42","author":"Yamada","year":"2014","journal-title":"J. Craniomaxillofac. Surg."},{"key":"B187","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1289\/ehp.59-1568075","article-title":"Fetal PCB syndrome: clinical features, intrauterine growth retardation and possible alteration in calcium metabolism","volume":"59","author":"Yamashita","year":"1985","journal-title":"Environ. Health Perspect."},{"key":"B188","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1093\/toxsci\/kfy301","article-title":"Effects of organophosphate ester flame retardants on endochondral ossification in ex vivo murine limb bud cultures","volume":"168","author":"Yan","year":"2019","journal-title":"Toxicol. Sci."},{"key":"B189","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1007\/s10735-024-10331-0","article-title":"Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the immune system maternal-fetal interface during palatal development","volume":"56","author":"Yongkai","year":"2024","journal-title":"J. Mol. Histol."},{"key":"B190","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.toxlet.2024.09.001","article-title":"Identification of competing endogenous RNA networks associated with circRNA and lncRNA in TCDD-induced cleft palate development","volume":"401","author":"Yu","year":"2024","journal-title":"Toxicol. Lett."},{"key":"B191","doi-asserted-by":"publisher","first-page":"2270","DOI":"10.1016\/j.fct.2012.04.032","article-title":"2,3,7,8-Tetrachlorodibenzo-p-dioxin induces a proteomic pattern that defines cleft palate formation in mice","volume":"50","author":"Yuan","year":"2012","journal-title":"Food Chem. Toxicol."},{"key":"B192","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.3892\/mmr.2016.5348","article-title":"Histone acetylation is involved in TCDD-induced cleft palate formation in fetal mice","volume":"14","author":"Yuan","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"B193","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1597\/15-211","article-title":"Comparative study of folic acid and \u03b1-naphthoflavone on reducing TCDD-induced cleft palate in fetal mice","volume":"54","author":"Yuan","year":"2017","journal-title":"Cleft Palate Craniofac. J."},{"key":"B194","doi-asserted-by":"publisher","first-page":"225","DOI":"10.3390\/ijms19010225","article-title":"Aryl hydrocarbon receptor antagonists mitigate the effects of dioxin on critical cellular functions in differentiating human osteoblast-like cells","volume":"19","author":"Yun","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"B195","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.devcel.2015.02.006","article-title":"Pax3 and Pax7 play essential safeguard functions against environmental stress-induced birth defects","volume":"33","author":"Zalc","year":"2015","journal-title":"Dev. Cell"},{"key":"B196","doi-asserted-by":"publisher","first-page":"5396","DOI":"10.3892\/mmr.2018.8521","article-title":"Alterations in DNA methyltransferases and methyl-CpG binding domain proteins during cleft palate formation as induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice","volume":"17","author":"Zhang","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"B197","doi-asserted-by":"publisher","first-page":"108731","DOI":"10.1016\/j.reprotox.2024.108731","article-title":"AKT\/mTOR-mediated autophagic signaling is associated with TCDD-induced cleft palate","volume":"130","author":"Zhang","year":"","journal-title":"Reprod. Toxicol."},{"key":"B198","doi-asserted-by":"publisher","first-page":"169918","DOI":"10.1016\/j.scitotenv.2024.169918","article-title":"Chronic di(2-ethylhexyl) phthalate exposure at environmental-relevant doses induces osteoporosis by disturbing the differentiation of bone marrow mesenchymal stem cells","volume":"914","author":"Zhang","year":"","journal-title":"Sci. Total Environ."},{"key":"B199","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1631\/jzus.B1300083","article-title":"Effect of vitamin B12 on cleft palate induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin and dexamethasone in mice","volume":"15","author":"Zhao","year":"2014","journal-title":"J. Zhejiang Univ. Sci. B"}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1878726\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T07:46:03Z","timestamp":1787125563000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1878726\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,19]]},"references-count":198,"alternative-id":["10.3389\/fcell.2026.1878726"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2026.1878726","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,19]]},"article-number":"1878726"}}