Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome

Abstract Trisomy of human chromosome 21 (Down syndrome, DS) alters development of multiple organ systems, including the face and underlying skeleton. Besides causing stigmata, these facial dysmorphologies can impair vital functions such as hearing, breathing, mastication, and health. To investigate...

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Autores principales:	John M. Starbuck, Sergi Llambrich, Rubèn Gonzàlez, Julia Albaigès, Anna Sarlé, Jens Wouters, Alejandro González, Xavier Sevillano, James Sharpe, Rafael De La Torre, Mara Dierssen, Greetje Vande Velde, Neus Martínez-Abadías
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/da08f0e1061a4569a2997947254eceb4
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spelling	oai:doaj.org-article:da08f0e1061a4569a2997947254eceb42021-12-02T15:52:59ZGreen tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome10.1038/s41598-021-83757-12045-2322https://doaj.org/article/da08f0e1061a4569a2997947254eceb42021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83757-1https://doaj.org/toc/2045-2322Abstract Trisomy of human chromosome 21 (Down syndrome, DS) alters development of multiple organ systems, including the face and underlying skeleton. Besides causing stigmata, these facial dysmorphologies can impair vital functions such as hearing, breathing, mastication, and health. To investigate the therapeutic potential of green tea extracts containing epigallocatechin-3-gallate (GTE-EGCG) for alleviating facial dysmorphologies associated with DS, we performed an experimental study with continued pre- and postnatal treatment with two doses of GTE-EGCG supplementation in a mouse model of DS, and an observational study of children with DS whose parents administered EGCG as a green tea supplement. We evaluated the effect of high (100 mg/kg/day) or low doses (30 mg/kg/day) of GTE-EGCG, administered from embryonic day 9 to post-natal day 29, on the facial skeletal development in the Ts65Dn mouse model. In a cross-sectional observational study, we assessed the facial shape in DS and evaluated the effects of self-medication with green tea extracts in children from 0 to 18 years old. The main outcomes are 3D quantitative morphometric measures of the face, acquired either with micro-computed tomography (animal study) or photogrammetry (human study). The lowest experimentally tested GTE-EGCG dose improved the facial skeleton morphology in a mouse model of DS. In humans, GTE-EGCG supplementation was associated with reduced facial dysmorphology in children with DS when treatment was administered during the first 3 years of life. However, higher GTE-EGCG dosing disrupted normal development and increased facial dysmorphology in both trisomic and euploid mice. We conclude that GTE-EGCG modulates facial development with dose-dependent effects. Considering the potentially detrimental effects observed in mice, the therapeutic relevance of controlled GTE-EGCG administration towards reducing facial dysmorphology in young children with Down syndrome has yet to be confirmed by clinical studies.John M. StarbuckSergi LlambrichRubèn GonzàlezJulia AlbaigèsAnna SarléJens WoutersAlejandro GonzálezXavier SevillanoJames SharpeRafael De La TorreMara DierssenGreetje Vande VeldeNeus Martínez-AbadíasNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q John M. Starbuck Sergi Llambrich Rubèn Gonzàlez Julia Albaigès Anna Sarlé Jens Wouters Alejandro González Xavier Sevillano James Sharpe Rafael De La Torre Mara Dierssen Greetje Vande Velde Neus Martínez-Abadías Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome
description	Abstract Trisomy of human chromosome 21 (Down syndrome, DS) alters development of multiple organ systems, including the face and underlying skeleton. Besides causing stigmata, these facial dysmorphologies can impair vital functions such as hearing, breathing, mastication, and health. To investigate the therapeutic potential of green tea extracts containing epigallocatechin-3-gallate (GTE-EGCG) for alleviating facial dysmorphologies associated with DS, we performed an experimental study with continued pre- and postnatal treatment with two doses of GTE-EGCG supplementation in a mouse model of DS, and an observational study of children with DS whose parents administered EGCG as a green tea supplement. We evaluated the effect of high (100 mg/kg/day) or low doses (30 mg/kg/day) of GTE-EGCG, administered from embryonic day 9 to post-natal day 29, on the facial skeletal development in the Ts65Dn mouse model. In a cross-sectional observational study, we assessed the facial shape in DS and evaluated the effects of self-medication with green tea extracts in children from 0 to 18 years old. The main outcomes are 3D quantitative morphometric measures of the face, acquired either with micro-computed tomography (animal study) or photogrammetry (human study). The lowest experimentally tested GTE-EGCG dose improved the facial skeleton morphology in a mouse model of DS. In humans, GTE-EGCG supplementation was associated with reduced facial dysmorphology in children with DS when treatment was administered during the first 3 years of life. However, higher GTE-EGCG dosing disrupted normal development and increased facial dysmorphology in both trisomic and euploid mice. We conclude that GTE-EGCG modulates facial development with dose-dependent effects. Considering the potentially detrimental effects observed in mice, the therapeutic relevance of controlled GTE-EGCG administration towards reducing facial dysmorphology in young children with Down syndrome has yet to be confirmed by clinical studies.
format	article
author	John M. Starbuck Sergi Llambrich Rubèn Gonzàlez Julia Albaigès Anna Sarlé Jens Wouters Alejandro González Xavier Sevillano James Sharpe Rafael De La Torre Mara Dierssen Greetje Vande Velde Neus Martínez-Abadías
author_facet	John M. Starbuck Sergi Llambrich Rubèn Gonzàlez Julia Albaigès Anna Sarlé Jens Wouters Alejandro González Xavier Sevillano James Sharpe Rafael De La Torre Mara Dierssen Greetje Vande Velde Neus Martínez-Abadías
author_sort	John M. Starbuck
title	Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome
title_short	Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome
title_full	Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome
title_fullStr	Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome
title_full_unstemmed	Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome
title_sort	green tea extracts containing epigallocatechin-3-gallate modulate facial development in down syndrome
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/da08f0e1061a4569a2997947254eceb4
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Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome

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