Maldonado Bautista, EstelaMurillo González, Jorge AlfonsoBarrio Asensio, María Del CarmenRío Sevilla, Aurora DelPérez De Miguelsanz, María JulianaLópez Gordillo, YamilaPartearroyo, TeresaParadas Lara, IreneMaestro De Las Casas, María Del CarmenMartínez Sanz, ElenaVarela Moreiras, GregorioMartínez Álvarez, María Concepción2024-02-152024-02-152011Maldonado, 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), 406-420.1422-640510.1159/000323213https://hdl.handle.net/20.500.14352/101452Folic 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.engjournal articlehttps://doi.org/10.1159/000323213https://pubmed.ncbi.nlm.nih.gov/21293104/restricted access612.015.641.7611Dietary folic-acid deficiencyCleft palateTGF-beta3Ciencias Biomédicas24 Ciencias de la Vida32 Ciencias Médicas