title: TCDD disrupts posterior palatogenesis and causes cleft palate.
abstract: Dioxins (e.g. 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD) cause cleft palate at a high rate. A post-fusional split may contribute to the pathogenesis, and tissue fragility may be a concern. The objective of this study was to investigate the effects of TCDD on the palatal epithelium, bone and muscle, which contribute to tissue integrity. ICR mice (10-12 weeks old) were used. TCDD was administered on E12.5 at 40 mg/kg. Immunohistochemical staining for AhR, ER-α, laminin, collagen IV, osteopontin, Runx2, MyoD, and desmin were performed. Furthermore, western blot analysis for osteopontin, Runx2, MyoD, and desmin were performed to evaluate protein expression in the palatal tissue. Immunohistologically, there was little difference in the collagen IV and laminin localization in the palatal epithelium between control versus TCDD-treated mice. Runx2 and osteopontin immunoreactivity decreased in the TCDD-treated palatal bone, and MyoD and desmin decreased in the TCDD-treated palatal muscle. AhR and ER-α immunoreactivity were localized to the normal palatal bone, but ER-α was diminished in the TCDD-treated palate. On western blot analysis, Runx2, MyoD, and desmin were all downregulated in the TCDD-treated palate. TCDD may suppress palatal osteogenesis and myogenesis via AhR, and cause cleft palates via a post-fusional split mechanism, in addition to a failure of palatal fusion.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Kochi Medical School, Kochi University (Head: Prof. Tetsuya Yamamoto), Kohasu, Oko-cho, Nankoku-City, Kochi 783-8505, Japan. Electronic address: tyamada@kochi-u.ac.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Anatomy and Cell Biology, Division of Life Sciences, Osaka Medical College (Head: Prof. Yoshinori Otsuki), 2-7, Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Azumi
authors.initials: A
authors.lastname: Hirata
authors.affiliation: Department of Oral and Maxillofacial Surgery, Kochi Medical School, Kochi University (Head: Prof. Tetsuya Yamamoto), Kohasu, Oko-cho, Nankoku-City, Kochi 783-8505, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Sasabe
authors.affiliation: Department of Oral and Maxillofacial Surgery, Kochi Medical School, Kochi University (Head: Prof. Tetsuya Yamamoto), Kohasu, Oko-cho, Nankoku-City, Kochi 783-8505, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Yoshimura
authors.affiliation: Department of Oral and Maxillofacial Surgery, Kochi Medical School, Kochi University (Head: Prof. Tetsuya Yamamoto), Kohasu, Oko-cho, Nankoku-City, Kochi 783-8505, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Ohno
authors.affiliation: Department of Oral and Maxillofacial Surgery, Kochi Medical School, Kochi University (Head: Prof. Tetsuya Yamamoto), Kohasu, Oko-cho, Nankoku-City, Kochi 783-8505, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Kitamura
authors.affiliation: Department of Oral and Maxillofacial Surgery, Kochi Medical School, Kochi University (Head: Prof. Tetsuya Yamamoto), Kohasu, Oko-cho, Nankoku-City, Kochi 783-8505, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000187:drug effects; D015153:Blotting, Western; D002972:Cleft Palate / Q000139:chemically induced* / Q000196:embryology; D024141:Collagen Type IV / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000187:drug effects; D003893:Desmin / Q000187:drug effects; D015536:Down-Regulation; D004848:Epithelium / Q000187:drug effects / Q000196:embryology; D047628:Estrogen Receptor alpha / Q000187:drug effects; D005260:Female; D005865:Gestational Age; D007150:Immunohistochemistry; D007797:Laminin / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D024510:Muscle Development / Q000187:drug effects; D017570:MyoD Protein / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D053495:Osteopontin / Q000187:drug effects; D010156:Palatal Muscles / Q000187:drug effects / Q000196:embryology; D010159:Palate / Q000187:drug effects* / Q000196:embryology; D021362:Palate, Hard / Q000187:drug effects / Q000196:embryology; D000072317:Polychlorinated Dibenzodioxins / Q000009:adverse effects*; D011247:Pregnancy; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects; D013723:Teratogens
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D024141:Collagen Type IV; D050659:Core Binding Factor Alpha 1 Subunit; D003893:Desmin; D047628:Estrogen Receptor alpha; D007797:Laminin; D017570:MyoD Protein; D053495:Osteopontin; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D013723:Teratogens; C484722:Ahr protein, mouse; C057363:MyoD1 myogenic differentiation protein; C493716:Runx2 protein, mouse; C506896:Spp1 protein, mouse
keywords: Cleft palate; Myogenesis; Osteogenesis; Post-fusional split; Posterior palate; TCDD