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Changes in Dietary Protein, Amino Acids, Folate and Other Nutrients or Toxins Regulate Embryonic and Fetal Growth and Development: Implications for Transgenerational Metabolic Disorders in Adults

A special issue of International Journal of Environmental Research and Public Health (ISSN 1660-4601). This special issue belongs to the section "Environmental Health".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 22415

Special Issue Editors

Prof. Dr. Lon Jeffrey Van Winkle

E-Mail Website
Guest Editor
1. Department of Biochemistry, Midwestern University, Downers Grove, IL 60515, USA
2. Department of Medical Humanities, Rocky Vista University, 8401 S. Chambers Road, Parker, CO 80134, USA
Interests: developmental origins of health and disease; environmentally-induced epigenetic modifications and human health; cultural diversity and bias mitigation; relationship-centered teaching and care; interprofessional education and public health
Special Issues, Collections and Topics in MDPI journals
Dr. Rebecca Jean Ryznar

E-Mail Website
Assistant Guest Editor
Molecular Biology, Department of Biomedical Sciences, Rocky Vista University, Parker, CO 80134, USA
Interests: epigenetic clock; epigenetic changes during aging; developmental epigenetics

Special Issue Information

Dear Colleagues,

The developmental origins of health and disease (Barker) hypothesis posits that maternal and paternal lifestyle variations, such as changes in diet, can alter early embryo development through both genetic and epigenetic modifications that may last a lifetime. When the environmental exposure leads to more permanent epigenetic modifications in sex cells or very early embryos, it causes transgenerational transmission of traits even in the absence of further environmental exposure of subsequent generations. During early embryo development, the epigenetic reprogramming window is a critical period for environmental factors, such as increases or decreases in dietary protein, amino acids, folate, and other nutrients or toxins, to cause permanent changes in epigenetic modifications and resultant disease susceptibility. Papers addressing these and related topics are invited for this Special Issue, including those presenting new findings as well as ones reviewing the field more broadly. Works to mitigate such harmful dietary effects are also encouraged.

Prof. Lon Jeffrey Van Winkle
Dr. Rebecca Jean Ryznar
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Environmental Research and Public Health is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2500 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Dietary protein
  • Amino acids
  • Folate
  • Toxins
  • One-carbon metabolism
  • Epigenetic modification
  • Metabolic syndrome
  • Embryo development
  • Fetal growth
  • Transgenerational metabolic disorders
  • Developmental origins of health and disease

Published Papers (6 papers)

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Research

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20 pages, 1873 KiB  
Article
Naringin Supplementation during Pregnancy Induces Sex and Region-Specific Alterations in the Offspring’s Brain Redox Status
by Bernardo Gindri dos Santos, Caroline Peres Klein, Mariana Scortegagna Crestani, Rafael Moura Maurmann, Régis Mateus Hözer, Karoline dos Santos Rodrigues, Pauline Maciel August and Cristiane Matté
Int. J. Environ. Res. Public Health 2021, 18(9), 4805; https://doi.org/10.3390/ijerph18094805 - 30 Apr 2021
Cited by 1 | Viewed by 1950
Abstract
Research has shown the beneficial effects of naringin supplementation to adult rodents, which can ameliorate oxidative stress in disease models. However, evidence has demonstrated that polyphenol supplementation induced detrimental effects when consumed during sensitive periods of development, such as pregnancy. Therefore, we investigated [...] Read more.
Research has shown the beneficial effects of naringin supplementation to adult rodents, which can ameliorate oxidative stress in disease models. However, evidence has demonstrated that polyphenol supplementation induced detrimental effects when consumed during sensitive periods of development, such as pregnancy. Therefore, we investigated the effect of maternal naringin supplementation during pregnancy on the offspring’s cerebral redox status. Pregnant Wistar rats were divided into control and naringin groups and supplemented from gestational day 15 to gestational day 21. On postnatal days 1, 7, and 21, offspring were euthanized, and the prefrontal cortex, hippocampus, striatum, and cerebellum dissected. On postnatal day 1, maternal naringin supplementation positively modulated the pups’ brain redox status. On postnatal day 7, a pro-oxidative milieu was observed in the offspring’s striatum and cerebellum in a sex-dependent manner, even though the prefrontal cortex and hippocampus were not negatively affected. Besides, the alterations observed on postnatal day 7 did not persist up to weaning. Our findings demonstrated that the effect induced by naringin supplementation in the brain redox status differed according to the period of development in which naringin was consumed since the beneficial effects usually found in the adult rodents became detrimental when the supplementation was applied during pregnancy. Full article
(This article belongs to the Special Issue Changes in Dietary Protein, Amino Acids, Folate and Other Nutrients or Toxins Regulate Embryonic and Fetal Growth and Development: Implications for Transgenerational Metabolic Disorders in Adults)
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9 pages, 623 KiB  
Article
Lysine Deprivation during Maternal Consumption of Low-Protein Diets Could Adversely Affect Early Embryo Development and Health in Adulthood
by Lon J. Van Winkle, Vasiliy Galat and Philip M. Iannaccone
Int. J. Environ. Res. Public Health 2020, 17(15), 5462; https://doi.org/10.3390/ijerph17155462 - 29 Jul 2020
Cited by 7 | Viewed by 2098
Abstract
The conversion of lysine to glutamate is needed for signaling in all plants and animals. In mouse embryonic stem (mES) cells, and probably their progenitors, endogenous glutamate production and signaling help maintain cellular pluripotency and proliferation, although the source of glutamate is yet [...] Read more.
The conversion of lysine to glutamate is needed for signaling in all plants and animals. In mouse embryonic stem (mES) cells, and probably their progenitors, endogenous glutamate production and signaling help maintain cellular pluripotency and proliferation, although the source of glutamate is yet to be determined. If the source of glutamate is lysine, then lysine deprivation caused by maternal low-protein diets could alter early embryo development and, consequently, the health of the offspring in adulthood. For these reasons, we measured three pertinent variables in human embryonic stem (hES) cells as a model for the inner cell masses of human blastocysts. We found that RNA encoding the alpha-aminoadipic semialdehyde synthase enzyme, which regulates glutamate production from lysine, was highly expressed in hES cells. Moreover, the mean amount of lysine consumed by hES cells was 50% greater than the mean amount of glutamate they produced, indicating that lysine is likely converted to glutamate in these cells. Finally, hES cells expressed RNA encoding at least two glutamate receptors. Since this may also be the case for hES progenitor cells in blastocysts, further studies are warranted to verify the presence of this signaling process in hES cells and to determine whether lysine deprivation alters early mammalian embryo development. Full article
(This article belongs to the Special Issue Changes in Dietary Protein, Amino Acids, Folate and Other Nutrients or Toxins Regulate Embryonic and Fetal Growth and Development: Implications for Transgenerational Metabolic Disorders in Adults)
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Review

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12 pages, 375 KiB  
Review
Epigenetic Modifications at the Center of the Barker Hypothesis and Their Transgenerational Implications
by Rebecca Jean Ryznar, Lacie Phibbs and Lon J. Van Winkle
Int. J. Environ. Res. Public Health 2021, 18(23), 12728; https://doi.org/10.3390/ijerph182312728 - 2 Dec 2021
Cited by 11 | Viewed by 3425
Abstract
Embryo/fetal nutrition and the environment in the reproductive tract influence the subsequent risk of developing adult diseases and disorders, as formulated in the Barker hypothesis. Metabolic syndrome, obesity, heart disease, and hypertension in adulthood have all been linked to unwanted epigenetic programing in [...] Read more.
Embryo/fetal nutrition and the environment in the reproductive tract influence the subsequent risk of developing adult diseases and disorders, as formulated in the Barker hypothesis. Metabolic syndrome, obesity, heart disease, and hypertension in adulthood have all been linked to unwanted epigenetic programing in embryos and fetuses. Multiple studies support the conclusion that environmental challenges, such as a maternal low-protein diet, can change one-carbon amino acid metabolism and, thus, alter histone and DNA epigenetic modifications. Since histones influence gene expression and the program of embryo development, these epigenetic changes likely contribute to the risk of adult disease onset not just in the directly affected offspring, but for multiple generations to come. In this paper, we hypothesize that the effects of parental nutritional status on fetal epigenetic programming are transgenerational and warrant further investigation. Numerous studies supporting this hypothesis are reviewed, and potential research techniques to study these transgenerational epigenetic effects are offered. Full article
(This article belongs to the Special Issue Changes in Dietary Protein, Amino Acids, Folate and Other Nutrients or Toxins Regulate Embryonic and Fetal Growth and Development: Implications for Transgenerational Metabolic Disorders in Adults)
27 pages, 2357 KiB  
Review
Redox Regulation and Oxidative Stress in Mammalian Oocytes and Embryos Developed In Vivo and In Vitro
by Madeleine L. M. Hardy, Margot L. Day and Michael B. Morris
Int. J. Environ. Res. Public Health 2021, 18(21), 11374; https://doi.org/10.3390/ijerph182111374 - 29 Oct 2021
Cited by 40 | Viewed by 6468
Abstract
Oocytes and preimplantation embryos require careful regulation of the redox environment for optimal development both in vivo and in vitro. Reactive oxygen species (ROS) are generated throughout development as a result of cellular metabolism and enzyme reactions. ROS production can result in [...] Read more.
Oocytes and preimplantation embryos require careful regulation of the redox environment for optimal development both in vivo and in vitro. Reactive oxygen species (ROS) are generated throughout development as a result of cellular metabolism and enzyme reactions. ROS production can result in (i) oxidative eustress, where ROS are helpful signalling molecules with beneficial physiological functions and where the redox state of the cell is maintained within homeostatic range by a closely coupled system of antioxidants and antioxidant enzymes, or (ii) oxidative distress, where excess ROS are deleterious and impair normal cellular function. in vitro culture of embryos exacerbates ROS production due to a range of issues including culture-medium composition and laboratory culture conditions. This increase in ROS can be detrimental not only to assisted reproductive success rates but can also result in epigenetic and genetic changes in the embryo, resulting in transgenerational effects. This review examines the effects of oxidative stress in the oocyte and preimplantation embryo in both the in vivo and in vitro environment, identifies mechanisms responsible for oxidative stress in the oocyte/embryo in culture and approaches to reduce these problems, and briefly examines the potential impacts on future generations. Full article
(This article belongs to the Special Issue Changes in Dietary Protein, Amino Acids, Folate and Other Nutrients or Toxins Regulate Embryonic and Fetal Growth and Development: Implications for Transgenerational Metabolic Disorders in Adults)
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19 pages, 759 KiB  
Review
Amino Acids and the Early Mammalian Embryo: Origin, Fate, Function and Life-Long Legacy
by Henry J. Leese, Paul J. McKeegan and Roger G. Sturmey
Int. J. Environ. Res. Public Health 2021, 18(18), 9874; https://doi.org/10.3390/ijerph18189874 - 19 Sep 2021
Cited by 23 | Viewed by 3707
Abstract
Amino acids are now recognised as having multiple cellular functions in addition to their traditional role as constituents of proteins. This is well-illustrated in the early mammalian embryo where amino acids are now known to be involved in intermediary metabolism, as energy substrates, [...] Read more.
Amino acids are now recognised as having multiple cellular functions in addition to their traditional role as constituents of proteins. This is well-illustrated in the early mammalian embryo where amino acids are now known to be involved in intermediary metabolism, as energy substrates, in signal transduction, osmoregulation and as intermediaries in numerous pathways which involve nitrogen metabolism, e.g., the biosynthesis of purines, pyrimidines, creatine and glutathione. The amino acid derivative S-adenosylmethionine has emerged as a universal methylating agent with a fundamental role in epigenetic regulation. Amino acids are now added routinely to preimplantation embryo culture media. This review examines the routes by which amino acids are supplied to the early embryo, focusing on the role of the oviduct epithelium, followed by an outline of their general fate and function within the embryo. Functions specific to individual amino acids are then considered. The importance of amino acids during the preimplantation period for maternal health and that of the conceptus long term, which has come from the developmental origins of health and disease concept of David Barker, is discussed and the review concludes by considering the potential utility of amino acid profiles as diagnostic of embryo health. Full article
(This article belongs to the Special Issue Changes in Dietary Protein, Amino Acids, Folate and Other Nutrients or Toxins Regulate Embryonic and Fetal Growth and Development: Implications for Transgenerational Metabolic Disorders in Adults)
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19 pages, 1305 KiB  
Review
Environmental Exposures around Conception: Developmental Pathways Leading to Lifetime Disease Risk
by Tom P. Fleming, Congshan Sun, Oleg Denisenko, Laura Caetano, Anan Aljahdali, Joanna M. Gould and Pooja Khurana
Int. J. Environ. Res. Public Health 2021, 18(17), 9380; https://doi.org/10.3390/ijerph18179380 - 6 Sep 2021
Cited by 14 | Viewed by 3934
Abstract
Environment around conception can influence the developmental programme with lasting effects on gestational and postnatal phenotype and with consequences for adult health and disease risk. Peri-conception exposure comprises a crucial part of the ‘Developmental Origins of Health and Disease’ (DOHaD) concept. In this [...] Read more.
Environment around conception can influence the developmental programme with lasting effects on gestational and postnatal phenotype and with consequences for adult health and disease risk. Peri-conception exposure comprises a crucial part of the ‘Developmental Origins of Health and Disease’ (DOHaD) concept. In this review, we consider the effects of maternal undernutrition experienced during the peri-conception period in select human models and in a mouse experimental model of protein restriction. Human datasets indicate that macronutrient deprivation around conception affect the epigenome, with enduring effects on cardiometabolic and neurological health. The mouse model, comprising maternal low protein diet exclusively during the peri-conception period, has revealed a stepwise progression in altered developmental programming following induction through maternal metabolite deficiency. This progression includes differential effects in extra-embryonic and embryonic cell lineages and tissues, leading to maladaptation in the growth trajectory and increased chronic disease comorbidities. The timeline embraces an array of mechanisms across nutrient sensing and signalling, cellular, metabolic, epigenetic and physiological processes with a coordinating role for mTORC1 signalling proposed. Early embryos appear active participants in environmental sensing to optimise the developmental programme for survival but with the trade-off of later disease. Similar adverse health outcomes may derive from other peri-conception environmental experiences, including maternal overnutrition, micronutrient availability, pollutant exposure and assisted reproductive treatments (ART) and support the need for preconception health before pregnancy. Full article
(This article belongs to the Special Issue Changes in Dietary Protein, Amino Acids, Folate and Other Nutrients or Toxins Regulate Embryonic and Fetal Growth and Development: Implications for Transgenerational Metabolic Disorders in Adults)
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