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
11 results
Search Results
Now showing 1 - 10 of 11
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 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 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 Immunohistochemical, histomorphometric, and gingival crevicular fluid analysis of residual and shallow periodontal pockets in patients with periodontitis Stages III and IV(Journal of Periodontology, 2019) Martínez Villa, Sergio; Sanz Martín, Ignacio; Maldonado Bautista, Estela; Virto Ruiz, Leire; Sanz Esporrín, Javier; Sanz Alonso, MarianoBackground: To study the differences between shallow and residual periodontal pockets in patients with periodontitis (Stages III and IV) after non-surgical periodontal treatment. Methods: Twenty patients diagnosed of periodontitis who were scheduled for periodontal surgery were included. In each patient, a palatal shallow site (≤3 mm) and a residual site (≥5 mm) were selected and GCF samples were processed by Luminex® analysis to determine the concentrations of interleukins (IL-1β, IL-6, IL-10, and IL-17a). During the periodontal surgery gingival biopsies were collected and processed for histo-morphometric and immunohistochemical evaluation to determine the extent of connective tissue inflammatory infiltrate (CTII) using the following markers (CD4, CD5, CD8, CD14, CD19, Elastase, and Syndecan). Mean differences between shallow and residual pockets samples, as well as correlations between GCF cytokine concentrations, area of CTII, and cellularity of the CTII were calculated. Results: A total of 15 patients were finally included, with analysis of 30 histological specimens and 30 GCF samples. Residual pockets presented significantly higher mean GCF volume, higher mean area of CTII and higher concentrations of IL-1β and IL-6 in GCF than shallow pockets. A significant correlation was detected between IL-10 levels and the CTII area, IL-10 and the percentage of Syndecan, and the area of CTII and the percentages of CD14 and Syndecan. Conclusions: The concentration of GCF cytokines did not correlate with the area of CTII measured histologically. A residual CTII and elevated concentrations of proinflammatory cytokines and cells were present in all sites 2 months after non-surgical treatment. The lack of healthy controls does not allow to establish differences between both groups.Item Maternal folic acid supplementation reduces the severity of cleft palate in Tgf-β3 null mutant mice(Pediatric research, 2019) López Gordillo, Yamila; Maldonado Bautista, Estela; Nogales, Laura; Río Sevilla, Aurora Del; Barrio Asensio, María Del Carmen; Murillo González, Jorge Alfonso; Martínez Sanz, Elena; Paradas Lara, Irene; Alonso Revuelta, María Isabel; Partearroyo, Teresa; Martínez Álvarez, María ConcepciónBACKGROUND: Cleft palate (CP) constitutes the most frequently seen orofacial cleft and is often associated with low folate status. Folate plays an essential role in the human body as a major coenzyme in one-carbon metabolism, including DNA synthesis, repair, and methylation. Whether the administration of isolated folic acid (FA) supplements prevents the CP caused by genetic mutations is unknown, as is its effect on the mechanisms leading to palate fusion. METHODS: FA was administered to females from two different strains of transforming growth factor β3 heterozygous mice. Null mutant progeny of these mice exhibit CP in 100% of cases of varying severity. We measured cleft length, height of palatal shelf adhesion, and the number of proliferating mesenchymal cells. Immunohistochemistry was also carried for collagen IV, laminin, fibronectin, cytokeratin-17, and EGF. RESULTS: FA supplementation significantly reduced CP severity and improved palatal shelf adhesion in both strains both in vivo and in vitro. Medial edge epithelium proliferation increased, and its differentiation was normalized as indicated by the presence and disposition of collagen IV, laminin, fibronectin, and cytokeratin-17. CONCLUSIONS: A maternal FA supplementation reduces the CP appearance by improving the mechanisms leading to palatal shelf adhesion.Item Analysis of the presence of cell proliferation-related molecules in the Tgf-β3 null mutant mouse palate reveals misexpression of EGF and Msx-1(Cells Tissues Organs, 2011) Del Río, A; López-Gordillo, Y; Martínez, M L; Barrio Asensio, María Del Carmen; Murillo Arroyo, Francisco Javier; Maldonado Bautista, Estela; Martínez Sanz, Elena; Martínez Álvarez, María ConcepciónThe Tgf-β3 null mutant mouse palate presents several cellular anomalies that lead to the appearance of cleft palate. One of them concerns the cell proliferation of both the palatal medial edge epithelium and mesenchyme. In this work, our aim was to determine whether there was any variation in the presence/distribution of several cell proliferation-related molecules that could be responsible for the cell proliferation defects observed in these palates. Our results showed no difference in the presence of EGF-R, PDGF-A, TGF-β2, Bmp-2, and Bmp-4, and differences were minimal for FGF-10 and Shh. However, the expression of EGF and Msx-1 changed substantially. The shift of the EGF protein expression was the one that most correlated with that of cell proliferation. This molecule is regulated by TGF-β3, and experiments blocking its activity in culture suggest that EGF misexpression in the Tgf-β3 null mutant mouse palate plays a role in the cell proliferation defect observed.