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Developmental Impairments in a Rat Model of Methyl Donor Deficiency: Effects of a Late Maternal Supplementation with Folic Acid

Vitamins B9 (folate) and B12 act as methyl donors in the one-carbon metabolism which influences epigenetic mechanisms. We previously showed that an embryofetal deficiency of vitamins B9 and B12 in the rat increased brain expression of let-7a and miR-34a microRNAs involved in the developmental contro...

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Autores principales: Geoffroy, Andréa, Saber-Cherif, Lynda, Pourié, Grégory, Helle, Déborah, Umoret, Rémy, Guéant, Jean-Louis, Bossenmeyer-Pourié, Carine, Daval, Jean-Luc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413039/
https://www.ncbi.nlm.nih.gov/pubmed/30813413
http://dx.doi.org/10.3390/ijms20040973
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author Geoffroy, Andréa
Saber-Cherif, Lynda
Pourié, Grégory
Helle, Déborah
Umoret, Rémy
Guéant, Jean-Louis
Bossenmeyer-Pourié, Carine
Daval, Jean-Luc
author_facet Geoffroy, Andréa
Saber-Cherif, Lynda
Pourié, Grégory
Helle, Déborah
Umoret, Rémy
Guéant, Jean-Louis
Bossenmeyer-Pourié, Carine
Daval, Jean-Luc
author_sort Geoffroy, Andréa
collection PubMed
description Vitamins B9 (folate) and B12 act as methyl donors in the one-carbon metabolism which influences epigenetic mechanisms. We previously showed that an embryofetal deficiency of vitamins B9 and B12 in the rat increased brain expression of let-7a and miR-34a microRNAs involved in the developmental control of gene expression. This was reversed by the maternal supply with folic acid (3 mg/kg/day) during the last third of gestation, resulting in a significant reduction of associated birth defects. Since the postnatal brain is subject to intensive developmental processes, we tested whether further folate supplementation during lactation could bring additional benefits. Vitamin deficiency resulted in weaned pups (21 days) in growth retardation, delayed ossification, brain atrophy and cognitive deficits, along with unchanged brain level of let-7a and decreased expression of miR-34a and miR-23a. Whereas maternal folic acid supplementation helped restore the levels of affected microRNAs, it led to a reduction of structural and functional defects taking place during the perinatal/postnatal periods, such as learning/memory capacities. Our data suggest that a gestational B-vitamin deficiency could affect the temporal control of the microRNA regulation required for normal development. Moreover, they also point out that the continuation of folate supplementation after birth may help to ameliorate neurological symptoms commonly associated with developmental deficiencies in folate and B12.
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spelling pubmed-64130392019-03-29 Developmental Impairments in a Rat Model of Methyl Donor Deficiency: Effects of a Late Maternal Supplementation with Folic Acid Geoffroy, Andréa Saber-Cherif, Lynda Pourié, Grégory Helle, Déborah Umoret, Rémy Guéant, Jean-Louis Bossenmeyer-Pourié, Carine Daval, Jean-Luc Int J Mol Sci Article Vitamins B9 (folate) and B12 act as methyl donors in the one-carbon metabolism which influences epigenetic mechanisms. We previously showed that an embryofetal deficiency of vitamins B9 and B12 in the rat increased brain expression of let-7a and miR-34a microRNAs involved in the developmental control of gene expression. This was reversed by the maternal supply with folic acid (3 mg/kg/day) during the last third of gestation, resulting in a significant reduction of associated birth defects. Since the postnatal brain is subject to intensive developmental processes, we tested whether further folate supplementation during lactation could bring additional benefits. Vitamin deficiency resulted in weaned pups (21 days) in growth retardation, delayed ossification, brain atrophy and cognitive deficits, along with unchanged brain level of let-7a and decreased expression of miR-34a and miR-23a. Whereas maternal folic acid supplementation helped restore the levels of affected microRNAs, it led to a reduction of structural and functional defects taking place during the perinatal/postnatal periods, such as learning/memory capacities. Our data suggest that a gestational B-vitamin deficiency could affect the temporal control of the microRNA regulation required for normal development. Moreover, they also point out that the continuation of folate supplementation after birth may help to ameliorate neurological symptoms commonly associated with developmental deficiencies in folate and B12. MDPI 2019-02-23 /pmc/articles/PMC6413039/ /pubmed/30813413 http://dx.doi.org/10.3390/ijms20040973 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Geoffroy, Andréa
Saber-Cherif, Lynda
Pourié, Grégory
Helle, Déborah
Umoret, Rémy
Guéant, Jean-Louis
Bossenmeyer-Pourié, Carine
Daval, Jean-Luc
Developmental Impairments in a Rat Model of Methyl Donor Deficiency: Effects of a Late Maternal Supplementation with Folic Acid
title Developmental Impairments in a Rat Model of Methyl Donor Deficiency: Effects of a Late Maternal Supplementation with Folic Acid
title_full Developmental Impairments in a Rat Model of Methyl Donor Deficiency: Effects of a Late Maternal Supplementation with Folic Acid
title_fullStr Developmental Impairments in a Rat Model of Methyl Donor Deficiency: Effects of a Late Maternal Supplementation with Folic Acid
title_full_unstemmed Developmental Impairments in a Rat Model of Methyl Donor Deficiency: Effects of a Late Maternal Supplementation with Folic Acid
title_short Developmental Impairments in a Rat Model of Methyl Donor Deficiency: Effects of a Late Maternal Supplementation with Folic Acid
title_sort developmental impairments in a rat model of methyl donor deficiency: effects of a late maternal supplementation with folic acid
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413039/
https://www.ncbi.nlm.nih.gov/pubmed/30813413
http://dx.doi.org/10.3390/ijms20040973
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