title: All-Trans Retinoic Acid-Induced Craniofacial Malformation Model: A Prenatal and Postnatal Morphological Analysis.
abstract: To characterize the prenatal and postnatal craniofacial bone development in mouse model of all-trans retinoic acid (ATRA) exposure at different ages by a quantitative and morphological analysis of skull morphology.
  
  
  
  Pregnant mice were exposed to ATRA at embryonic day 10 (E10) and 13 (E13) by oral gavage. Skulls of mice embryos at E19.5 and adult mice at postnatal day 35 (P35) were collected for high-resolution microcomputed tomography (microCT) imaging scanning and section HE staining. Reconstruction and measurement of mouse skulls were performed for prenatal and postnatal analysis of the control and ATRA-exposed mice.
  
  
  
  Craniofacial malformations in mouse models caused by ATRA exposure were age dependent. ATRA exposure at E10 induced cleft palate in 81.8% of the fetuses, whereas the palatine bone of E13-exposed mice was intact. Inhibitions of maxilla and mandible development with craniofacial asymmetry induced were observed at E19.5 and P35. Compared with control and E13-exposed mice, the palatine bones of E10-exposed mice were not elevated and were smaller in dimension. Some E10-exposed mice exhibited other craniofacial abnormalities, including premature fusion of mandibular symphysis with a missing mandibular incisor and a smaller mandible. Severe deviated snouts and amorphous craniofacial suture were detected in E13-exposed mice at P35.
  
  
  
  These morphological variations in E10- and E13-exposed mice suggested that ATRA was teratogenic in craniofacial bone development in mice and the effect was age dependent.
authors.forename: Weicai
authors.initials: W
authors.lastname: Wang
authors.forename: Yutao
authors.initials: Y
authors.lastname: Jian
authors.forename: Bin
authors.initials: B
authors.lastname: Cai
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.forename: Mu
authors.initials: M
authors.lastname: Chen
authors.forename: Hongzhang
authors.initials: H
authors.lastname: Huang
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D019465:Craniofacial Abnormalities / Q000139:chemically induced* / Q000000981:diagnostic imaging; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D011247:Pregnancy; D011857:Radiographic Image Interpretation, Computer-Assisted; D014212:Tretinoin / Q000633:toxicity*; D055114:X-Ray Microtomography
chemical_list: D014212:Tretinoin
keywords: all-trans-retinoic acid; cleft palate; craniofacial bone; craniofacial malformations; high-resolution microCT