Person: Martínez Sanz, Elena
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First Name
Elena
Last Name
Martínez Sanz
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Anatomía y Embriología
Area
Anatomía y Embriología Humana
Identifiers
5 results
Search Results
Now showing 1 - 5 of 5
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 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 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.