Person: Maldonado Bautista, Estela
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First Name
Estela
Last Name
Maldonado Bautista
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Anatomía y Embriología
Area
Anatomía y Embriología Humana
Identifiers
14 results
Search Results
Now showing 1 - 10 of 14
Item Tongue Abnormalities Are Associated to a Maternal Folic Acid Deficient Diet in Mice(Nutrients, 2017) Maldonado Bautista, Estela; López-Gordillo, Yamila; Partearroyo, Teresa; Varela Moreiras, Gregorio; Martínez Álvarez, Concepción; Pérez Miguelsanz, JulianaIt is widely accepted that maternal folic acid (FA) deficiency during pregnancy is a risk factor for abnormal development. The tongue, with multiple genes working together in a coordinated cascade in time and place, has emerged as a target organ for testing the effect of FA during development. A FA-deficient (FAD) diet was administered to eight-week-old C57/BL/6J mouse females for 2–16 weeks. Pregnant dams were sacrificed at gestational day 17 (E17). The tongues and heads of 15 control and 210 experimental fetuses were studied. In the tongues, the maximum width, base width, height and area were compared with width, height and area of the head. All measurements decreased from 10% to 38% with increasing number of weeks on maternal FAD diet. Decreased head and tongue areas showed a harmonic reduction (Spearman nonparametric correlation, Rho = 0.802) with respect to weeks on a maternal FAD diet. Tongue congenital abnormalities showed a 10.9% prevalence, divided in aglossia (3.3%) and microglossia (7.6%), always accompanied by agnathia (5.6%) or micrognathia (5.2%). This is the first time that tongue alterations have been related experimentally to maternal FAD diet in mice. We propose that the tongue should be included in the list of FA-sensitive birth defect organs due to its relevance in several key food and nutrition processes.Item Papel del ácido fólico dietético en el desarrollo del paladar de ratón(2012) Maldonado Bautista, Estela; Martínez Álvarez, María Concepción; Pérez de Miguelsanz, María Juliana; Murillo González, Jorge AlfonsoUn correcto desarrollo del paladar implica una actuación concreta de los mecanismos básicos causantes de la palatogénesis y sus alteraciones pueden desencadenar fisura palatina (FP). Existen genes estrechamente relacionados con la palatogénesis, como TGF-β3, cuyo bloqueo en ratones ocasiona FP, y factores ambientales, como el déficit de ácido fólico (AF), que se asocian a la aparición de fisuras cuando coexisten otros factores de riesgo. Se utilizaron ratones de la cepa C57 silvestres, cuyas hembras fueron sometidas a una dieta carente de AF entre 2 y 16 semanas, y ratones C57 mutantes para el gen Tgf-β3, cuyas hembras fueron alimentadas de 2 a 16 semanas con una dieta que contenía veinte veces más AF que la dieta control. El nivel de AF fue analizado en el hígado de las hembras por análisis microbiológico, comprobando así la efectividad de las dietas suministradas. Los embriones se analizaron macroscópicamente y su paladar histológicamente. Paladares de embriones deficitarios se emplearon para realizar cultivos con los que se analizaron mecanismos básicos implicados en la palatogénesis: proliferación celular, muerte celular, adhesión y fusión de los procesos palatinos. En este tipo de embriones se analizó la expresión de TGF- β3 en el paladar y los cultivos fueron repetidos añadiendo TGF-β3 al medio de cultivo. Los embriones mutantes sometidos al suplemento de AF, tras el análisis macroscópico e histológico, se emplearon para la medida de la proliferación celular y se realizaron cultivos con sus paladares para analizar la adhesión y fusión de los procesos palatinos. Los embriones deficitarios mostraron alteraciones en todos los mecanismos básicos de la palatogénesis desde las 2 semanas de dieta y FP completa a partir de las 8 semanas. Se registró un descenso de la expresión de TGF-β3 y una reversión a los niveles control de los mecanismos alterados ante la presencia de TGF-β3 en el medio de cultivo. Lo que significa que existe una relación entre déficit dietético de AF y la alteración de la expresión de TGF-β3 y del desarrollo embrionario del paladar. Los embriones mutantes sometidos al suplemento de AF presentaron un menor número de FP completas, un aumento de la proliferación y la adhesión palatinas. Parece que el suplemento de AF genera una mejora en la manifestación de la FP de los mutantes con el gen de Tgf- β3 bloqueado. Concluimos que la carencia de AF genera alteraciones en los mecanismos por los que tienen lugar la palatogénesis al interferir con la expresión de TGF-β3 y que un suplemento dietético de AF disminuye la gravedad de la FP.Item 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, 2011) Maldonado Bautista, Estela; Murillo González, Jorge Alfonso; Barrio Asensio, María Del Carmen; Río Sevilla, Aurora Del; Pérez De Miguelsanz, María Juliana; López Gordillo, Yamila; Partearroyo, Teresa; Paradas Lara, Irene; Maestro De Las Casas, María Del Carmen; Martínez Sanz, Elena; Varela Moreiras, Gregorio; Martínez Álvarez, María ConcepciónFolic 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.Item A new technique for feeding dogs with a congenital cleft palate for surgical research(Laboratory Animals, 2011) López-Gordillo, Yamila et al.; González-Meli, B; Martínez Sanz, Elena; Casado Gómez, Inmaculada; Martín Álvaro, María Concepción; González Aranda, Pablo; Paradas Lara, Irene; Maldonado Bautista, Estela; Maestro De Las Casas, María Del Carmen; Prados Frutos, Juan Carlos; Martínez Álvarez, María ConcepciónIn humans, cleft palate (CP) is one of the most common malformations. Although surgeons use palatoplasty to close CP defects in children, its consequences for subsequent facial growth have prompted investigations into other novel surgical alternatives. The animal models of CP used to evaluate new surgical treatments are frequently obtained by creating surgically induced clefts in adult dogs. This procedure has been ethically criticized due to its severity and questionable value as an animal model for human CP. Dogs born with a congenital CP would be much better for this purpose, provided they developed CP at a sufficient rate and could be fed. Up until now, feeding these pups carried the risk of aspiration pneumonia, while impeding normal suckling and chewing, and thus compromising orofacial growth. We developed a technique for feeding dog pups with CP from birth to the time of surgery using two old Spanish pointer dog pups bearing a complete CP. This dog strain develops CP in 15-20% of the offspring spontaneously. Custom-made feeding teats and palatal prostheses adapted to the pups' palates were made from thermoplastic plates. This feeding technique allowed lactation, eating and drinking in the pups with CP, with only sporadic rhinitis. To determine whether the use of this palatal prosthesis interferes with palatal growth, the palates of three littermate German shorthaired pointer pups without CP, either wearing or not wearing (controls) the prosthesis, were measured. The results showed that the permanent use of this prosthesis does not impede palatal growth in the pups.Item Interactions between TGF-beta1 and TGF-beta3 and their role in medial edge epithelium cell death and palatal fusion in vitro(Differentiation, 2009) Murillo Arroyo, Francisco Javier; Maldonado Bautista, Estela; Barrio MC; Río Sevilla, Aurora Del; López, Y; Martínez Sanz, Elena; González, I; Martín Álvaro, María Concepción; Casado Gómez, Inmaculada; Martínez Álvarez, María ConcepciónIn recent decades, studies have shown that both TGF-b1 and TGF-b3 play an important role in the induction of medial edge epithelium (MEE) cell death and palatal fusion. Many of these experiments involved the addition or blockage of one of these growth factors in wild-type (WT) mouse palate cultures, where both TGF-b1 and TGF-b3 are present. Few studies have addressed the existence of interactions between TGF-b1 and TGF-b3, which could modify their individual roles in MEE cell death during palatal fusion. We carried out several experiments to test this possibility, and to investigate how this could influence TGF-b1 and TGF-b3 actions on MEE cell death and palatal shelf fusion. We double immunolabelled developing mouse palates with anti-TGF-b1 or anti-TGF-b3 antibodies and TUNEL, added rhTGF-b1 or rhTGF-b3 or blocked the TGF-b1 and TGF-b3 action at different concentrations to WT or Tgf-b3 null mutant palate cultures, performed in situ hybridizations with Tgf-b1 or Tgf-b3 riboprobes, and measured the presence of TUNEL-positive midline epithelial seam (MES) cells and MES disappearance (palatal shelf fusion) in the different in vitro conditions. By combining all these experiments, we demonstrate great interaction between TGF-b1 and TGF-b3 in the developing palate and confirm that TGF-b3 has a more active role in MES cell death than TGF-b1, although both are major inductors of MES disappearance. Finally, the co-localization of TGF-b1, but not TGF-b3, with TUNEL in the MES allows us to suggest a possible role for TGF-b1 in MES apoptotic clearance.Item Transforming Growth Factor-β3 Regulates Adipocyte Number in Subcutaneous White Adipose Tissue(CELL REPORTS, 2017) Petrus, Paul et al.; Rydén M.; Maldonado Bautista, Estela; Martínez Álvarez, María ConcepciónWhite adipose tissue (WAT) mass is determined by adipocyte size and number. While adipocytes are continuously turned over, the mechanisms controlling fat cell number in WAT upon weight changes are unclear. Herein, prospective studies of human subcutaneous WAT demonstrate that weight gain increases both adipocyte size and number, but the latter remains unaltered after weight loss. Transcriptome analyses associate changes in adipocyte number with the expression of 79 genes. This gene set is enriched for growth factors, out of which one, transforming growth factor-b3 (TGFb3), stimulates adipocyte progenitor proliferation, resulting in a higher number of cells undergoing differentiation in vitro. The relevance of these observations was corroborated in vivo where Tgfb3+/ mice, in comparison with wild-type littermates, display lower subcutaneous adipocyte progenitor proliferation, WAT hypertrophy, and glucose intolerance. TGFb3 is therefore a regulator of subcutaneous adipocyte number and may link WAT morphology to glucose metabolism.Item Epidermal Growth Factor Impairs Palatal Shelf Adhesion and Fusion in the T gf-β3 Null Mutant(Cells Tissues Organs, 2014) Barrio Asensio, María Del Carmen; Río Sevilla, Aurora Del; Murillo González, Jorge Alfonso; Maldonado Bautista, Estela; López Gordillo, Yamila; Paradas Lara, Irene; Hernandes, Luzmarina; Catón Vázquez, Javier; Martínez Álvarez, ConcepciónThe cleft palate presented by transforming growth factor-β3 (Tgf-β3 ) null mutant mice is caused by altered palatal shelf adhesion, cell proliferation, epithelial-to-mesenchymal transformation and cell death. The expression of epidermal growth factor (EGF), transforming growth factor-β1 ( Tgf-β1 ) and muscle segment homeobox-1 (Msx-1) is modified in the palates of these knockout mice, and the cell proliferation defect is caused by the change in EGF expression. In this study, we aimed to determine whether this change in EGF expression has any effect on the other mechanisms altered in Tgf-β 3 knockout mouse palates. We tested the effect of inhibiting EGF activity in vitro in the knockout palates via the addition of Tyrphostin AG 1478. We also investigated possible interactions between EGF, Tgf-β 1 and Msx-1 in Tgf-β 3 null mouse palate cultures. The results show that the inhibition of EGF activity in Tgf-β 3 null mouse palate cultures improves palatal shelf adhesion and fusion, with a particular effect on cell death, and restores the normal distribution pattern of Msx-1 in the palatal esenchyme. Inhibition of TGF-β 1 does not affect either EGF or Msx-1 expression.Item Alteration of medial-edge epithelium cell adhesion in two Tgf-beta3 null mouse strains(Differentiation, 2008) Martínez Sanz, Elena; Río Sevilla, Aurora Del; Barrio Asensio, María Del Carmen; Maldonado Bautista, Estela; Murillo González, Jorge Alfonso; Garcillán, B; Amorós, M; Fuerte, T; Fernández, A; Trinidad, E; Rabadán, MA; López, Y; Martínez Salmeán, María Luisa; Martínez Álvarez, María ConcepciónAlthough palatal shelf adhesion is a crucial event during palate development, little work has been carried out to determine which molecules are responsible for this process. Furthermore, whether altered palatal shelf adhesion causes the cleft palate presented by Tgf-b3 null mutant mice has not yet been clarified. Here, we study the presence/distribution of some extracellular matrix and cell adhesion molecules at the time of the contact of palatal shelves in both wild-type and Tgf-b3 null mutant palates of two strains of mice (C57/BL/6J(C57), and MF1) that develop cleft palates of different severity. We have performed immunohistochemistry with antibodies against collagens IV and IX, laminin, fibronectin, the a5- and b1-integrins, and ICAM-1; in situ hybridization with a Nectin-1 riboprobe; and palatal shelf cultures treated or untreated with TGF-b3 or neutralizing antibodies against fibronectin or the a5-integrin. Our results show the location of these molecules in the wild-type mouse medial edge epithelium (MEE) of both strains at the time of the contact of palatal shelves; the heavier (C57) and milder (MF1) alteration of their presence in the Tgf-b3 null mutants; the importance of TGF-b3 to restore their normal pattern of expression; and the crucial role of fibronectin and the a5-integrin in palatal shelf adhesion. We thus provide insight into the molecular bases of this important process and the cleft palate presented by Tgf-b3 null mutant mice.Item Maxillary growth in a congenital cleft palate canine model for surgical research(Journal of Cranio-Maxillofacial Surgery, 2014) Paradas Lara, Irene; Casado Gómez, Inmaculada; Martín, Conchita; Martínez Sanz, Elena; López Gordillo, Yamila; González, Pablo; Rodríguez Bobada, Cruz; Chamorro, Manuel; Arias, Pablo; Maldonado Bautista, Estela; Ortega Aranegui, Ricardo; Berenguer, Beatriz; Martínez Álvarez, María ConcepciónWe have recently presented the Old Spanish Pointer dog, with a 15-20% spontaneous congenital cleft palate rate, as a unique experimental model of this disease. This study aimed to describe the cleft palate of these dogs for surgical research purposes and to determine whether congenital cleft palate influences maxillofacial growth. Seven newborn Old Spanish Pointer dogs of both sexes, comprising a cleft palate group (n = 4) and a normal palate group (n = 3), were fed using the same technique. Macroscopic photographs and plaster casts from the palate, lateral radiographs and computer tomograms of the skull were taken sequentially over 41 weeks, starting at week 5. The cleft morphology, the size and the tissue characteristics in these dogs resembled the human cleft better than current available animal models. During growth, the cleft width varies. Most of the transverse and longitudinal measures of the palate were statistically lower in the cleft palate group. The cleft palate group showed hypoplasia of the naso-maxillary complex. This model of congenital cleft palate seems suitable for surgical research purposes. A reduced maxillofacial pre- and post-natal development is associated to the congenital cleft palate in the Old Spanish Pointer dog.Item Interactions between TGF-β1 and TGF-β3 and their role in medial edge epithelium cell death and palatal fusion in vitro(Differentiation, 2008) Murillo González, Jorge Alfonso; Maldonado Bautista, Estela; Barrio Asensio, María Del Carmen; Río Sevilla, Aurora Del; López, Yamila; Martínez Sanz, Elena; González, Ignacio; Martín, Concepción; Casado, Inmaculada; Martínez Álvarez, María ConcepciónIn recent decades, studies have shown that both TGF-beta(1) and TGF-beta(3) play an important role in the induction of medial edge epithelium (MEE) cell death and palatal fusion. Many of these experiments involved the addition or blockage of one of these growth factors in wild-type (WT) mouse palate cultures, where both TGF-beta(1) and TGF-beta(3) are present. Few studies have addressed the existence of interactions between TGF-beta(1) and TGF-beta(3), which could modify their individual roles in MEE cell death during palatal fusion. We carried out several experiments to test this possibility, and to investigate how this could influence TGF-beta(1) and TGF-beta(3) actions on MEE cell death and palatal shelf fusion. We double-immunolabelled developing mouse palates with anti-TGF-beta(1) or anti-TGF-beta(3) antibodies and TUNEL, added rhTGF-beta(1) or rhTGF-beta(3) or blocked the TGF-beta(1) and TGF-beta(3) action at different concentrations to WT or Tgf-beta(3) null mutant palate cultures, performed in situ hybridizations with Tgf-beta(1) or Tgf-beta(3) riboprobes, and measured the presence of TUNEL-positive midline epithelial seam (MES) cells and MES disappearance (palatal shelf fusion) in the different in vitro conditions. By combining all these experiments, we demonstrate great interaction between TGF-beta(1) and TGF-beta(3) in the developing palate and confirm that TGF-beta(3) has a more active role in MES cell death than TGF-beta(1), although both are major inductors of MES disappearance. Finally, the co-localization of TGF-beta(1), but not TGF-beta(3), with TUNEL in the MES allows us to suggest a possible role for TGF-beta(1) in MES apoptotic clearance.