title: Amniotic fluid induces rapid epithelialization in the experimentally ruptured fetal mouse palate--implications for fetal wound healing.
abstract: Cleft of the secondary palate is one of the most common congenital birth defects in humans. The primary cause of cleft palate formation is a failure of fusion of bilateral palatal shelves, but rupture of the once fused palate has also been suggested to take place in utero. The possibility of post-fusion rupture of the palate in humans has hardly been accepted, mainly because in all the cleft palate cases, the cleft palatal edge is always covered with intact epithelium. To verify whether the intrauterine environment of the fetus plays roles in wound healing when the once fused palate is torn apart, we artificially tore apart fetal mouse palates after fusion and cultivated them in culture medium with or without mouse or human amniotic fluid. We thereby found that the wounded palatal edge became completely covered with flattened epithelium after 36 hours in culture with amniotic fluid, but not in culture without amniotic fluid. Using histological and scanning electron microscopic analyses of the healing process, it was revealed that the epithelium covering the wound was almost exclusively derived from the adjacent nasal epithelium, but not from the oral epithelium. Such actions of amniotic fluid on the fetal wound were never simulated by exogenous epidermal growth factor (EGF), albumin, or both. In addition, the rapid epithelialization induced by amniotic fluid was not prevented by either PD168393 (an inhibitor of the EGF receptor-specific tyrosine kinase) or SB431542 (a specific inhibitor of TGFbeta receptor type I/ALK5). The present study provides new insights into the unique biological actions of amniotic fluid in the repair of injured fetal palate.
authors.affiliation: Department of Anatomy and Developmental Biology, Kyoto University Graduate School of Medicine, Kyoto, Japan. takigawa@cac.med.kyoto-u.ac.jp
authors.forename: Toshiya
authors.initials: T
authors.lastname: Takigawa
authors.forename: Kohei
authors.initials: K
authors.lastname: Shiota
mesh_terms: D030201:Activin Receptors, Type I / Q000378:metabolism; D000653:Amniotic Fluid / Q000378:metabolism*; D000818:Animals; D002972:Cleft Palate / Q000196:embryology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D005333:Fetus / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008855:Microscopy, Electron, Scanning; D009297:Nasal Mucosa / Q000196:embryology / Q000378:metabolism; D009924:Organ Culture Techniques / Q000379:methods; D010159:Palate / Q000166:cytology / Q000196:embryology* / Q000293:injuries* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D012421:Rupture; D014945:Wound Healing
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C000625842:Tgfbr1 protein, mouse