Maternal One-carbon Metabolism during the Periconceptional Period and Human Foetal Brain Growth: A Systematic Review

The maternal environment during the periconceptional period influences foetal growth and development, in part, via epigenetic mechanisms moderated by one-carbon metabolic pathways. During embryonic development, one-carbon metabolism is involved in brain development and neural programming. Derangements in one-carbon metabolism increase (i) the short-term risk of embryonic neural tube-related defects and (ii) long-term childhood behaviour, cognition, and autism spectrum disorders. Here we investigate the association between maternal one-carbon metabolism and foetal and neonatal brain growth and development. Database searching resulted in 26 articles eligible for inclusion. Maternal vitamin B6, vitamin B12, homocysteine, and choline were not associated with foetal and/or neonatal head growth. First-trimester maternal plasma folate within the normal range (> 17 nmol/L) associated with increased foetal head size and head growth, and high erythrocyte folate (1538–1813 nmol/L) with increased cerebellar growth, whereas folate deficiency (< 7 nmol/L) associated with a reduced foetal brain volume. Preconceptional folic acid supplement use and specific dietary patterns (associated with increased B vitamins and low homocysteine) increased foetal head size. Although early pregnancy maternal folate appears to be the most independent predictor of foetal brain growth, there is insufficient data to confirm the link between maternal folate and offspring risks for neurodevelopmental diseases.

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Commentary: One-carbon metabolism has major implications for fetal growth and development beyond neural tube defects

International Journal of Epidemiology ◽

10.1093/ije/dyu175 ◽

2014 ◽

Vol 43 (5) ◽

pp. 1498-1499 ◽

Cited By ~ 1

Author(s):

S. J. Lewis

Keyword(s):

Fetal Growth ◽

Neural Tube ◽

Neural Tube Defects ◽

Carbon Metabolism ◽

Growth And Development ◽

One Carbon Metabolism

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One carbon metabolism disturbances and the C677T MTHFR gene polymorphism in children with autism spectrum disorders

Journal of Cellular and Molecular Medicine ◽

10.1111/j.1582-4934.2008.00463.x ◽

2009 ◽

Vol 13 (10) ◽

pp. 4229-4238 ◽

Cited By ~ 67

Author(s):

Sergiu P. Paşca ◽

Eleonora Dronca ◽

Tamás Kaucsár ◽

Elena C. Crǎciun ◽

Emõke Endreffy ◽

...

Keyword(s):

Autism Spectrum Disorders ◽

Gene Polymorphism ◽

Carbon Metabolism ◽

Children With Autism ◽

Autism Spectrum ◽

Mthfr Gene ◽

C677t Mthfr ◽

Mthfr Gene Polymorphism ◽

Spectrum Disorders ◽

One Carbon Metabolism

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The periconceptional period, reproduction and long-term health of offspring: the importance of one-carbon metabolism

Human Reproduction Update ◽

10.1093/humupd/dmt041 ◽

2013 ◽

Vol 19 (6) ◽

pp. 640-655 ◽

Cited By ~ 161

Author(s):

R. P. M. Steegers-Theunissen ◽

J. Twigt ◽

V. Pestinger ◽

K. D. Sinclair

Keyword(s):

Carbon Metabolism ◽

Periconceptional Period ◽

One Carbon Metabolism

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Tetrahydrofolate biosynthesis and distribution in higher plants

Biochemical Society Transactions ◽

10.1042/bst0330758 ◽

2005 ◽

Vol 33 (4) ◽

pp. 758-762 ◽

Cited By ~ 27

Author(s):

T. Sahr ◽

S. Ravanel ◽

F. Rébeillé

Keyword(s):

Carbon Metabolism ◽

Growth And Development ◽

De Novo ◽

Higher Plants ◽

The Other ◽

Transfer Reactions ◽

Intracellular Traffic ◽

Vitamin B9 ◽

Carbon Transfer ◽

One Carbon Metabolism

One-carbon transfer reactions are mediated by H4F (tetrahydrofolate), a soluble coenzyme (vitamin B9) that is synthesized de novo by plants and microorganisms, and absorbed from the diet by animals. H4F synthesis in plants is quartered between the plastids, the cytosol and the mitochondria, a spatial distribution that is not observed in the other organisms and that suggests a complex intracellular traffic. Also, the activity of H4F synthesis fluctuates during plant growth, depending on the tissue and the developmental stage of the seedling, thus illustrating the flexibility of one-carbon metabolism in these organisms. This paper will focus on our recent knowledge about H4F synthesis in the plant cell and will briefly describe the activity of the pathway during the growth and development of the seedling.

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Multifaceted role of one-carbon metabolism on immunometabolic control and growth during pregnancy, lactation and the neonatal period in dairy cattle

Journal of Animal Science and Biotechnology ◽

10.1186/s40104-021-00547-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Danielle N. Coleman ◽

Abdulrahman S. Alharthi ◽

Yusheng Liang ◽

Matheus Gomes Lopes ◽

Vincenzo Lopreiato ◽

...

Keyword(s):

Oxidative Stress ◽

Dairy Cattle ◽

Carbon Metabolism ◽

Growth And Development ◽

Immune Dysfunction ◽

Production Performance ◽

Methyl Donors ◽

Methyl Donor ◽

One Carbon Metabolism ◽

And Oxidative Stress

AbstractDairy cattle undergo dramatic metabolic, endocrine, physiologic and immune changes during the peripartal period largely due to combined increases in energy requirements for fetal growth and development, milk production, and decreased dry matter intake. The negative nutrient balance that develops results in body fat mobilization, subsequently leading to triacylglycerol (TAG) accumulation in the liver along with reductions in liver function, immune dysfunction and a state of inflammation and oxidative stress. Mobilization of muscle and gluconeogenesis are also enhanced, while intake of vitamins and minerals is decreased, contributing to metabolic and immune dysfunction and oxidative stress. Enhancing post-ruminal supply of methyl donors is one approach that may improve immunometabolism and production synergistically in peripartal cows. At the cellular level, methyl donors (e.g. methionine, choline, betaine and folic acid) interact through one-carbon metabolism to modulate metabolism, immune responses and epigenetic events. By modulating those pathways, methyl donors may help increase the export of very low-density lipoproteins to reduce liver TAG and contribute to antioxidant synthesis to alleviate oxidative stress. Thus, altering one-carbon metabolism through methyl donor supplementation is a viable option to modulate immunometabolism during the peripartal period. This review explores available data on the regulation of one-carbon metabolism pathways in dairy cows in the context of enzyme regulation, cellular sensors and signaling mechanisms that might respond to increased dietary supply of specific methyl donors. Effects of methyl donors beyond the one-carbon metabolism pathways, including production performance, immune cell function, mechanistic target or rapamycin signaling, and fatty acid oxidation will also be highlighted. Furthermore, the effects of body condition and feeding system (total mixed ration vs. pasture) on one-carbon metabolism pathways are explored. Potential effects of methyl donor supply during the pepartum period on dairy calf growth and development also are discussed. Lastly, practical nutritional recommendations related to methyl donor metabolism during the peripartal period are presented. Nutritional management during the peripartal period is a fertile area of research, hence, underscoring the importance for developing a systems understanding of the potential immunometabolic role that dietary methyl donors play during this period to promote health and performance.

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Genetic Variation: Impact on Folate (and Choline) Bioefficacy

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000040 ◽

2010 ◽

Vol 80 (45) ◽

pp. 319-329 ◽

Cited By ~ 9

Author(s):

Allyson A. West ◽

Marie A. Caudill

Keyword(s):

Carbon Metabolism ◽

Genetic Variants ◽

Plasma Homocysteine ◽

Water Soluble ◽

Gene Interactions ◽

Dietary Folate ◽

Methyl Donors ◽

Common Genetic Variants ◽

One Carbon Metabolism ◽

The Impact

Folate and choline are water-soluble micronutrients that serve as methyl donors in the conversion of homocysteine to methionine. Inadequacy of these nutrients can disturb one-carbon metabolism as evidenced by alterations in circulating folate and/or plasma homocysteine. Among common genetic variants that reside in genes regulating folate absorptive and metabolic processes, homozygosity for the MTHFR 677C > T variant has consistently been shown to have robust effects on status markers. This paper will review the impact of genetic variants in folate-metabolizing genes on folate and choline bioefficacy. Nutrient-gene and gene-gene interactions will be considered along with the need to account for these genetic variants when updating dietary folate and choline recommendations.

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