title: Vitamin A and clefting: putative biological mechanisms.
abstract: Nutritional factors such as vitamin intake contribute to the etiology of cleft palate. Vitamin A is a regulator of embryonic development. Excess vitamin A can cause congenital malformations such as spina bifida and cleft palate. Therefore, preventive nutritional strategies are required. This review identifies putative biological mechanisms underlying the association between maternal vitamin A intake and cleft palate. Excessive vitamin A may disturb all three stages of palatogenesis: 1) during shelf outgrowth, it may decrease cell proliferation and thus prevent tissue development; 2) it may prevent shelf elevation by affecting extracellular matrix composition and hydration; and 3) during shelf fusion, it may affect epithelial differentiation and apoptosis, which precludes the formation of a continuous palate. In general, high doses of vitamin A affect palatogenesis through interference with cell proliferation and growth factors such as transforming growth factor β and platelet-derived growth factor. The effects of lower doses of vitamin A need to be investigated in greater depth in order to improve public health recommendations.
authors.affiliation: Department of Orthodontics and Craniofacial Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Mignon M G
authors.initials: MM
authors.lastname: Ackermans
authors.forename: Huiqing
authors.initials: H
authors.lastname: Zhou
authors.forename: Carine E L
authors.initials: CE
authors.lastname: Carels
authors.forename: Frank A D T G
authors.initials: FA
authors.lastname: Wagener
authors.forename: Johannes W
authors.initials: JW
authors.lastname: Von den Hoff
mesh_terms: D000818:Animals; D002972:Cleft Palate / Q000209:etiology*; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D018673:Nutrition Policy; D010159:Palate / Q000187:drug effects / Q000196:embryology; D011247:Pregnancy; D013723:Teratogens / Q000633:toxicity; D014212:Tretinoin / Q000633:toxicity; D014801:Vitamin A / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D013723:Teratogens; D014801:Vitamin A; D014212:Tretinoin