Epigenetic Mechanisms of Maternal Dietary Protein and Amino Acids Affecting Growth and Development of Offspring

Nutrients can regulate metabolic activities of living organisms through epigenetic mechanisms, including DNA methylation, histone modification, and RNA regulation. Since the nutrients required for early embryos and postpartum lactation are derived in whole or in part from maternal and lactating nutrition, the maternal nutritional level affects the growth and development of fetus and creates a profound relationship between disease development and early environmental exposure in the offspring’s later life. Protein is one of the most important biological macromolecules, involved in almost every process of life, such as information transmission, energy processing and material metabolism. Maternal protein intake levels may affect the integrity of the fetal genome and alter DNA methylation and gene expression. Most amino acids are supplied to the fetus from the maternal circulation through active transport of placenta. Some amino acids, such as methionine, as dietary methyl donor, play an important role in DNA methylation and body’s one-carbon metabolism. The purpose of this review is to describe effects of maternal dietary protein and amino acid intake on fetal and neonatal growth and development through epigenetic mechanisms, with examples in humans and animals.

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DNA methylation, ageing and the influence of early life nutrition

Proceedings of The Nutrition Society ◽

10.1017/s0029665114000081 ◽

2014 ◽

Vol 73 (3) ◽

pp. 413-421 ◽

Cited By ~ 28

Author(s):

Karen A. Lillycrop ◽

Samuel P. Hoile ◽

Leonie Grenfell ◽

Graham C. Burdge

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Early Life ◽

Later Life ◽

Well Being ◽

Ageing Process ◽

Specific Gene ◽

Epigenetic Mechanisms ◽

Associated Diseases ◽

Dna Nucleotide Sequence

It is well established that genotype plays an important role in the ageing process. However, recent studies have suggested that epigenetic mechanisms may also influence the onset of ageing-associated diseases and longevity. Epigenetics is defined as processes that induce heritable changes in gene expression without a change in the DNA nucleotide sequence. The major epigenetic mechanisms are DNA methylation, histone modification and non-coding RNA. Such processes are involved in the regulation of tissue-specific gene expression, cell differentiation and genomic imprinting. However, epigenetic dysregulation is frequently seen with ageing. Relatively little is known about the factors that initiate such changes. However, there is emerging evidence that the early life environment, in particular nutrition, in early life can induce long-term changes in DNA methylation resulting in an altered susceptibility to a range of ageing-associated diseases. In this review, we will focus on the changes in DNA methylation that occur during ageing; their role in the ageing process and how early life nutrition can modulate DNA methylation and influence longevity. Understanding the mechanisms by which diet in early life can influence the epigenome will be crucial for the development of preventative and intervention strategies to increase well-being in later life.

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Impacts of maternal dietary protein intake on fetal survival, growth, and development

Experimental Biology and Medicine ◽

10.1177/1535370218758275 ◽

2018 ◽

Vol 243 (6) ◽

pp. 525-533 ◽

Cited By ~ 34

Author(s):

Cassandra M Herring ◽

Fuller W Bazer ◽

Gregory A Johnson ◽

Guoyao Wu

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Dietary Protein ◽

Growth And Development ◽

Protein Intake ◽

Growth Restriction ◽

Dietary Protein Intake ◽

Fetal Survival ◽

Uterine Growth ◽

Intra Uterine Growth Restriction

Maternal nutrition during gestation, especially dietary protein intake, is a key determinant in embryonic survival, growth, and development. Low maternal dietary protein intake can cause embryonic losses, intra-uterine growth restriction, and reduced postnatal growth due to a deficiency in specific amino acids that are important for cell metabolism and function. Of note, high maternal dietary protein intake can also result in intra-uterine growth restriction and embryonic death, due to amino acid excesses, as well as the toxicity of ammonia, homocysteine, and H2S that are generated from amino acid catabolism. Maternal protein nutrition has a pronounced impact on fetal programming and alters the expression of genes in the fetal genome. As a precursor to the synthesis of molecules (e.g. nitric oxide, polyamines, and creatine) with cell signaling and metabolic functions, L-arginine (Arg) is essential during pregnancy for growth and development of the conceptus. With inadequate maternal dietary protein intake, Arg and other important amino acids are deficient in mother and fetus. Dietary supplementation of Arg during gestation has been effective in improving embryonic survival and development of the conceptus in many species, including humans, pigs, sheep, mice, and rats. Both the balance among amino acids and their quantity are critical for healthy pregnancies and offspring. Impact statement This review aims at: highlighting adverse effects of elevated levels of ammonia in mother or fetus on embryonic/fetal survival, growth, and development; helping nutritionists and practitioners to understand the mechanisms whereby elevated levels of ammonia in mother or fetus results in embryonic/fetal death, growth restriction, and developmental abnormalities; and bringing, into the attention of nutritionists and practitioners, the problems of excess or inadequate dietary intake of protein or amino acids on pregnancy outcomes in animals and humans. The article provides new, effective means to improve embryonic/fetal survival and growth in mammals.

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Nutrition during Pregnancy Impacts Offspring's Epigenetic Status—Evidence from Human and Animal Studies

Nutrition and Metabolic Insights ◽

10.4137/nmi.s29527 ◽

2015 ◽

Vol 8s1 ◽

pp. NMI.S29527 ◽

Cited By ~ 14

Author(s):

Aisling A. Geraghty ◽

Karen L. Lindsay ◽

Goiuri Alberdi ◽

Fionnuala M. McAuliffe ◽

Eileen R. Gibney

Keyword(s):

Dna Methylation ◽

Growth And Development ◽

Critical Period ◽

Animal Studies ◽

Maternal Nutrition ◽

Later Life ◽

Future Health ◽

Global Methylation ◽

Methyl Donors ◽

Methylation Patterns

Pregnancy is a vital time of growth and development during which maternal nutrition significantly influences the future health of both mother and baby. During pregnancy, the fetus experiences a critical period of plasticity. Epigenetics, specifically DNA methylation, plays an important role here. As nutrition is influential for DNA methylation, this review aims to determine if maternal nutrition during pregnancy can modify the offspring's epigenome at birth. Research focuses on micronutrients and methyl donors such as folate and B vitamins. Evidence suggests that maternal nutrition does not largely influence global methylation patterns, particularly in nutrient-replete populations; however, an important impact on gene-specific methylation is observed. A link is shown between maternal nutrition and the methylome of the offspring; however, there remains a paucity of research. With the potential to use DNA methylation patterns at birth to predict health of the child in later life, it is vital that further research be carried out.

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INSULIN-LIKE GROWTH FACTORS AND PLACENTAL FUNCTION

Fetal and Maternal Medicine Review ◽

10.1017/s0965539507001994 ◽

2007 ◽

Vol 18 (3) ◽

pp. 201-224

Author(s):

NATALIA SCHLABRITZ-LOUTSEVITCH ◽

CUN LI ◽

PETER W NATHANIELSZ

Keyword(s):

Amino Acids ◽

Fetal Growth ◽

Growth And Development ◽

Cellular Structure ◽

Building Blocks ◽

Maternal Circulation ◽

Nutritional Factors ◽

Placental Function ◽

Normal Trajectory ◽

Insulin Like Growth Factors

Placentas from different species differ not only in their cellular structure and normal trajectory of growth but also in the architecture of their placental vasculature and the transport and exchange mechanisms that determine nutritional transfer from mother to fetus and waste disposal from fetus to mother.1 Many maternal and fetal hormonal and nutritional factors, as well as placental paracrine and autocrine systems affect placental growth and development throughout gestation.2 Nutrients delivered from the maternal circulation are as important for placental growth as they are for fetal growth. In addition to passing across the placenta to provide the building blocks for fetal growth, amino acids, carbohydrate and lipids are incorporated into the placenta.

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Epigenetics, Nutrition, Disease and Drug Development

Current Drug Discovery Technologies ◽

10.2174/1570163815666180419154954 ◽

2019 ◽

Vol 16 (4) ◽

pp. 386-391 ◽

Cited By ~ 1

Author(s):

Kenneth Lundstrom

Keyword(s):

Dna Methylation ◽

Drug Discovery ◽

Rna Interference ◽

Nutritional Requirements ◽

Signal Pathways ◽

Disease Development ◽

Epigenetic Mechanisms ◽

Epigenetic Changes ◽

Health And Disease ◽

Novel Drug

Epigenetic mechanisms comprising of DNA methylation, histone modifications and gene silencing by RNA interference have been strongly linked to the development and progression of various diseases. These findings have triggered research on epigenetic functions and signal pathways as targets for novel drug discovery. Dietary intake has also presented significant influence on human health and disease development and nutritional modifications have proven important in prevention, but also the treatment of disease. Moreover, a strong link between nutrition and epigenetic changes has been established. Therefore, in attempts to develop novel safer and more efficacious drugs, both nutritional requirements and epigenetic mechanisms need to be addressed.

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New Aspects of the Epigenetics of Pancreatic Carcinogenesis

Epigenomes ◽

10.3390/epigenomes4030018 ◽

2020 ◽

Vol 4 (3) ◽

pp. 18

Author(s):

Murat Toruner ◽

Martin E. Fernandez-Zapico ◽

Christopher L. Pin

Keyword(s):

Pancreatic Cancer ◽

Dna Methylation ◽

Survival Rate ◽

Epigenetic Mechanisms ◽

Therapeutic Approaches ◽

Cancer Epigenetics ◽

Pancreatic Carcinogenesis ◽

New Therapeutic Approaches ◽

Environmental Events ◽

Underlying Pathogenesis

Pancreatic cancer remains among the deadliest forms of cancer with a 5 year survival rate less than 10%. With increasing numbers being observed, there is an urgent need to elucidate the pathogenesis of pancreatic cancer. While both contribute to disease progression, neither genetic nor environmental factors completely explain susceptibility or pathogenesis. Defining the links between genetic and environmental events represents an opportunity to understand the pathogenesis of pancreatic cancer. Epigenetics, the study of mitotically heritable changes in genome function without a change in nucleotide sequence, is an emerging field of research in pancreatic cancer. The main epigenetic mechanisms include DNA methylation, histone modifications and RNA interference, all of which are altered by changes to the environment. Epigenetic mechanisms are being investigated to clarify the underlying pathogenesis of pancreatic cancer including an increasing number of studies examining the role as possible diagnostic and prognostic biomarkers. These mechanisms also provide targets for promising new therapeutic approaches for this devastating malignancy.

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A Genome-Wide Integrative Association Study of DNA Methylation and Gene Expression Data and Later Life Cognitive Functioning in Monozygotic Twins

Frontiers in Neuroscience ◽

10.3389/fnins.2020.00233 ◽

2020 ◽

Vol 14 ◽

Cited By ~ 1

Author(s):

Mette Soerensen ◽

Dominika Marzena Hozakowska-Roszkowska ◽

Marianne Nygaard ◽

Martin J. Larsen ◽

Veit Schwämmle ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Cognitive Functioning ◽

Association Study ◽

Gene Expression Data ◽

Monozygotic Twins ◽

Later Life ◽

Expression Data ◽

Genome Wide ◽

A Genome

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The Role of Reduced Methionine in Mediating the Metabolic Responses to Protein Restriction Using Different Sources of Protein

Nutrients ◽

10.3390/nu13082609 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2609

Author(s):

Han Fang ◽

Kirsten P. Stone ◽

Sujoy Ghosh ◽

Laura A. Forney ◽

Thomas W. Gettys

Keyword(s):

Amino Acids ◽

Dietary Protein ◽

Target Genes ◽

Protein Restriction ◽

Metabolic Phenotype ◽

Sulfur Amino Acids ◽

Transcriptional Responses ◽

Similar Reduction ◽

Dietary Protein Restriction ◽

Methionine Restriction

Dietary protein restriction and dietary methionine restriction (MR) produce a comparable series of behavioral, physiological, biochemical, and transcriptional responses. Both dietary regimens produce a similar reduction in intake of sulfur amino acids (e.g., methionine and cystine), and both diets increase expression and release of hepatic FGF21. Given that FGF21 is an essential mediator of the metabolic phenotype produced by both diets, an important unresolved question is whether dietary protein restriction represents de facto methionine restriction. Using diets formulated from either casein or soy protein with matched reductions in sulfur amino acids, we compared the ability of the respective diets to recapitulate the metabolic phenotype produced by methionine restriction using elemental diets. Although the soy-based control diets supported faster growth compared to casein-based control diets, casein-based protein restriction and soy-based protein restriction produced comparable reductions in body weight and fat deposition, and similar increases in energy intake, energy expenditure, and water intake. In addition, the prototypical effects of dietary MR on hepatic and adipose tissue target genes were similarly regulated by casein- and soy-based protein restriction. The present findings support the feasibility of using restricted intake of diets from various protein sources to produce therapeutically effective implementation of dietary methionine restriction.

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DIGESTION OF NUTRIENTS IN THE SMALL INTESTINE OF PIGS FED DIETS CONTAINING RAW AND AUTOCLAVED FABA BEANS

Canadian Journal of Animal Science ◽

10.4141/cjas76-056 ◽

1976 ◽

Vol 56 (3) ◽

pp. 451-456 ◽

Cited By ~ 14

Author(s):

M. IVAN ◽

J. P. BOWLAND

Keyword(s):

Amino Acids ◽

Small Intestine ◽

Beneficial Effect ◽

Dietary Protein ◽

Dry Matter ◽

Latin Square ◽

Sole Source ◽

Intestinal Uptake ◽

Gross Energy ◽

Faba Beans

Four castrated pigs, each fitted with a re-entrant cannula in the terminal ileum, were used to study digestion in the small intestine. A nitrogen-free diet was used for the estimation of metabolic nitrogen and amino acids. Faba beans, as the sole source of dietary protein, were used raw or after autoclaving for 30 or 60 min. The four diets were fed to the pigs in a 4 × 4 latin square experiment. The pigs were fed each diet for 6 days prior to a 24-hr collection of total ileal contents. Autoclaving of faba beans had no significant effect on digestibility of dry matter, gross energy, nitrogen and individual amino acids except arginine, which was significantly increased. The intestinal uptake of arginine was the highest and of cystine the lowest in all faba bean diets. It was concluded that autoclaving faba beans had no beneficial effect on the digestion of nutrients in the small intestine of the pig.

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