RT Journal Article
T1 Occurrence of cleft-palate and alteration of Tgf-β3 expression and the mechanisms leading to palatal fusion in mice following dietary folic-acid deficiency
A1 Maldonado Bautista, Estela
A1 Murillo González, Jorge Alfonso
A1 Barrio Asensio, María Del Carmen
A1 Río Sevilla, Aurora Del
A1 Pérez De Miguelsanz, María Juliana
A1 López Gordillo, Yamila
A1 Partearroyo, Teresa
A1 Paradas Lara, Irene
A1 Maestro De Las Casas, María Del Carmen
A1 Martínez Sanz, Elena
A1 Varela Moreiras, Gregorio
A1 Martínez Álvarez, María Concepción
AB Folic acid (FA) is essential for numerous bodily functions. Its decrease during pregnancy has been associated with an increased risk of congenital malformations in the progeny. The relationship between FA deficiency and the appearance of cleft palate (CP) is controversial, and little information exists on a possible effect of FA on palate development. We investigated the effect of a 2–8 weeks’ induced FA deficiency in female mice on the development of CP in their progeny as well as the mechanisms leading to palatal fusion, i.e. cell proliferation, cell death, and palatal-shelf adhesion and fusion. We showed that an 8 weeks’ maternal FA deficiency caused complete CP in the fetuses although a 2 weeks’ maternal FA deficiency was enough to alter all the mechanisms analyzed. Since transforming growth factor beta 3 (TGF-β3) is crucial for palatal fusion and since most of the mechanisms impaired by FA deficiency were also observed in the palates of Tgf-β3 null mutant mice, we investigated the presence of TGF-beta 3 mRNA, its protein and phospho-SMAD2 in FA-deficient (FAD) mouse palates. Our results evidenced a large reduction in Tgf-β3 expression in palates of embryos of dams fed an FAD diet for 8 weeks; Tgf-β3 expression was less reduced in palates of embryos of dams fed an FAD diet for 2 weeks. Addition of Tgf-β3 to palatal-shelf cultures of embryos of dams fed an FAD diet for 2 weeks normalized all the altered mechanisms. Thus, an insufficient folate status may be a risk factor for the development of CP in mice, and exogenous Tgf-β3 compensates this deficit in vitro.
PB Karger
SN 1422-6405
YR 2011
FD 2011
LK https://hdl.handle.net/20.500.14352/101452
UL https://hdl.handle.net/20.500.14352/101452
LA eng
NO Maldonado, E., Murillo, J., Barrio, C., Del Río, A., Pérez-Miguelsanz, J., López-Gordillo, Y., ... & Martínez-Álvarez, C. (2011). Occurrence of Cleft-Palate and Alteration of Tgf-β3 Expression and the Mechanisms Leading to Palatal Fusion in Mice following Dietary Folic-Acid Deficiency. Cells Tissues Organs, 194(5), 406-420.
NO Ministerio de Sanidad (España)
NO Instituto de Salud Carlos III
NO Universidad Complutense de Madrid
NO Banco Santander
DS Docta Complutense
RD 17 abr 2025