Maternal folic acid supplementation reduces the severity of cleft palate in Tgf-β3 null mutant mice

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dc.contributor.authorLópez Gordillo, Yamila
dc.contributor.authorMaldonado Bautista, Estela
dc.contributor.authorNogales, Laura
dc.contributor.authorRío Sevilla, Aurora Del
dc.contributor.authorBarrio Asensio, María Del Carmen
dc.contributor.authorMurillo González, Jorge Alfonso
dc.contributor.authorMartínez Sanz, Elena
dc.contributor.authorParadas Lara, Irene
dc.contributor.authorAlonso Revuelta, María Isabel
dc.contributor.authorPartearroyo, Teresa
dc.contributor.authorMartínez Álvarez, María Concepción
dc.date.accessioned2024-01-19T08:41:08Z
dc.date.available2024-01-19T08:41:08Z
dc.date.issued2019-01-15
dc.description.abstractBACKGROUND: 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.
dc.description.departmentDepto. de Anatomía y Embriología
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Economía y Competitividad de España
dc.description.sponsorshipBanco Santander
dc.description.sponsorshipUniversidad Complutense de Madrid
dc.description.statuspub
dc.identifier.citationA, Barrio MC, Murillo J, Martínez-Sanz E, Paradas-Lara I, Alonso MI, Partearroyo T, Martínez-Álvarez C. Maternal folic acid supplementation reduces the severity of cleft palate in Tgf-β3 null mutant mice. Pediatr Res. 2019 Mar;85(4):566-573.
dc.identifier.doi10.1038/s41390-018-0267-6
dc.identifier.issn0031-3998
dc.identifier.officialurlhttps://www.nature.com/articles/s41390-018-0267-6
dc.identifier.relatedurlhttps://pubmed.ncbi.nlm.nih.gov/30683931/
dc.identifier.urihttps://hdl.handle.net/20.500.14352/93982
dc.issue.number4
dc.journal.titlePediatric research
dc.language.isoeng
dc.page.final573
dc.page.initial566
dc.publisherSPRINGERNATURE
dc.relation.projectIDPS09/01762
dc.relation.projectIDPR41/17-21009
dc.rights.accessRightsopen access
dc.subject.cdu616-053.2
dc.subject.keywordFolic acid
dc.subject.keywordCleft palate
dc.subject.keywordTgf-β3 null mutant
dc.subject.keywordMice
dc.subject.ucmMedicina
dc.subject.unesco3201.10 Pediatría
dc.titleMaternal folic acid supplementation reduces the severity of cleft palate in Tgf-β3 null mutant mice
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number85
dspace.entity.typePublication
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