{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:40:47Z","timestamp":1790278847004,"version":"4.1.0"},"reference-count":120,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T00:00:00Z","timestamp":1548892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H05889"],"award-info":[{"award-number":["16H05889"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dioxins and related compounds induce morphological abnormalities in developing animals in an aryl hydrocarbon receptor (AhR)-dependent manner. Here we review the studies in which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is used as a prototypical compound to elucidate the pathogenesis of morphological abnormalities. TCDD-induced cleft palate in fetal mice involves a delay in palatogenesis and dissociation of fused palate shelves. TCDD-induced hydronephrosis, once considered to be caused by the anatomical obstruction of the ureter, is now separated into TCDD-induced obstructive and non-obstructive hydronephrosis, which develops during fetal and neonatal periods, respectively. In the latter, a prostaglandin E2 synthesis pathway and urine concentration system are involved. TCDD-induced abnormal development of prostate involves agenesis of the ventral lobe. A suggested mechanism is that AhR activation in the urogenital sinus mesenchyme by TCDD modulates the wingless-type MMTV integration site family (WNT)\/\u03b2-catenin signaling cascade to interfere with budding from urogenital sinus epithelium. TCDD exposure to zebrafish embryos induces loss of epicardium progenitor cells and heart malformation. AHR2-dependent downregulation of Sox9b expression in cardiomyocytes is a suggested underlying mechanism. TCDD-induced craniofacial malformation in zebrafish is considered to result from the AHR2-dependent reduction in SRY-box 9b (SOX9b), probably partly via the noncoding RNA slincR, resulting in the underdevelopment of chondrocytes and cartilage.<\/jats:p>","DOI":"10.3390\/ijms20030617","type":"journal-article","created":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T03:08:05Z","timestamp":1548990485000},"page":"617","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Mechanisms of Developmental Toxicity of Dioxins and Related Compounds"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2854-087X","authenticated-orcid":false,"given":"Wataru","family":"Yoshioka","sequence":"first","affiliation":[{"name":"Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1061-6872","authenticated-orcid":false,"given":"Chiharu","family":"Tohyama","sequence":"additional","affiliation":[{"name":"Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","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":"Birnbaum","year":"2006","journal-title":"Toxicol. 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