Mild Choline Deficiency and MTHFD1 Synthetase Deficiency Interact to Increase Incidence of Developmental Delays and Defects in Mice.
Nutrients
; 14(1)2021 Dec 28.
Article
em En
| MEDLINE
| ID: mdl-35011003
ABSTRACT
Folate and choline are interconnected metabolically. The MTHFD1 R653Q SNP is a risk factor for birth defects and there are concerns that choline deficiency may interact with this SNP and exacerbate health risks. 80-90% of women do not meet the Adequate Intake (AI) for choline. The objective of this study was to assess the effects of choline deficiency on maternal one-carbon metabolism and reproductive outcomes in the MTHFD1-synthetase deficient mouse (Mthfd1S), a model for MTHFD1 R653Q. Mthfd1S+/+ and Mthfd1S+/- females were fed control (CD) or choline-deficient diets (ChDD; 1/3 the amount of choline) before mating and during pregnancy. Embryos were evaluated for delays and defects at 10.5 days gestation. Choline metabolites were measured in the maternal liver, and total folate measured in maternal plasma and liver. ChDD significantly decreased choline, betaine, phosphocholine, and dimethylglycine in maternal liver (p < 0.05, ANOVA), and altered phosphatidylcholine metabolism. Maternal and embryonic genotype, and diet-genotype interactions had significant effects on defect incidence. Mild choline deficiency and Mthfd1S+/- genotype alter maternal one-carbon metabolism and increase incidence of developmental defects. Further study is required to determine if low choline intakes contribute to developmental defects in humans, particularly in 653QQ women.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Deficiências do Desenvolvimento
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Deficiência de Colina
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Fenômenos Fisiológicos da Nutrição Materna
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Meteniltetra-Hidrofolato Cicloidrolase
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Enzimas Multifuncionais
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Formiato-Tetra-Hidrofolato Ligase
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Aminoidrolases
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Metilenotetra-Hidrofolato Desidrogenase (NADP)
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Complexos Multienzimáticos
Tipo de estudo:
Incidence_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Pregnancy
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article