Transgenerational Epigenetics - 1st Edition - ISBN: 9780124059443, 9780124059221

Transgenerational Epigenetics

1st Edition

Editors: Trygve Tollefsbol
eBook ISBN: 9780124059221
Hardcover ISBN: 9780124059443
Imprint: Academic Press
Published Date: 6th May 2014
Page Count: 412
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Transgenerational Epigenetics provides a comprehensive analysis of the inheritance of epigenetic phenomena between generations. Recent research points to the existence of biological phenomena that are controlled not through gene mutations, but rather through reversible and heritable epigenetic processes.

Epidemiological studies have suggested that environmental factors may be heritable. In fact, environmental factors often play a role in transgenerational epigenetics, which may have selective or adverse effects on the offspring. This epigenetic information can be transferred through a number of mechanisms including DNA methylation, histone modifications or RNA and the effects can persist for multiple generations.

This book examines the evolution of epigenetic inheritance, its expression in animal and plant models, and how human diseases, such as metabolic disorders and cardiovascular diseases, appear to be affected by transgenerational epigenetic inheritance. It discusses clinical interventions in transgenerational epigenetic inheritance that may be on the horizon to help prevent diseases before the offspring are born, or to reduce the severity of diseases at the very earliest stages of development in utero, and current controversies in this area of study, as well as future directions for research.

Key Features

  • Focused discussion of metabolic disorders, cardiovascular diseases and longevity, which appear most affected by reversible and heritable epigenetic processes
  • Encompasses both foundational and clinical aspects including discussions of preventative in utero therapies
  • Covers history, future outlook, disease management and current controversies


Graduate students researching the fundamental basis of epigenetics to therapeutic interventions into epigenetic-based disorders

Table of Contents

  • Preface
  • Chapter 1. Transgenerational Epigenetics
    • Introduction
    • Definition and History of Generational Epigenetic Inheritance
    • Germline Epigenetics
    • Epidemiology of Epigenetic Inheritance
    • Basic Mechanisms/Processes of Epigenetic Inheritance
    • Model Organisms
    • Evolution of Transgenerational Epigenetics
    • Parental Epigenetic Inheritance
    • Environmental Epigenetic Effects on the Offspring
    • Impact of Transgenerational Epigenetics on Disease
    • Clinical Significance of Transgenerational Epigenetics
    • Controversies and Debate of Generational Epigenetic Inheritance
    • Conclusion
  • Section I. Definitions and History of Generational Epigenetic Inheritance
    • Chapter 2. Definition of Epigenetic Transgenerational Inheritance and Biological Impacts
      • Introduction and Historical Context
      • Epigenetic Transgenerational Inheritance
      • Germline Epimutations
      • Transgenerational Inheritance of Disease and Phenotypic Variation
      • Transgenerational Disease Etiology
      • Impact and Future Studies
      • Glossary
    • Chapter 3. Historical Perspective of Transgenerational Epigenetics
      • Introduction
      • Shifting Paradigms of Heredity and Evolution
      • Early Evidence of Non-Mendelian Inheritance
      • The Origins of Epigenetics
      • Intersection of Phenomena and Mechanisms
      • Transgenerational Epigenetics in Ecology and Physiology
      • Conclusion
  • Section II. Germline Epigenetics
    • Chapter 4. Epigenetics and the Maternal Germline
      • Introduction
      • Transgenerational Inheritance in the Maternal Germline
      • Discussion
      • Future Directions
    • Chapter 5. Epigenetic Changes in the Paternal Germline
      • Introduction
      • PGC Epigenetic Reprogramming
      • Epigenetics of Meiotic Prophase I
      • Histone-to-Protamine Transition during Spermiogenesis
      • Zygotic Epigenetic Reprogramming
      • Transgenerational Epigenetic Inheritance, Aging, and Environmental Effects
      • Epigenetics in Male-Factor Infertility
      • Conclusions
  • Section III. Epidemiology of Epigenetic Inheritance
    • Chapter 6. Epidemiology of Transgenerational Epigenetics
      • Introduction
      • The Evidence for Transgenerational Epigenetics in Humans
      • Potential Mechanisms of Transgenerational Transmission: Transgenerational Epigenetic Inheritance
      • Summary
  • Section IV. Basic Mechanisms/Processes of Epigenetic Inheritance
    • Chapter 7. Metastable Epialleles
      • Definitions
      • Murine MEs
      • Human ME Candidates
      • Potential for THE Transgenerational Inheritance of MEs
    • Chapter 8. Towards the Molecular Mechanisms of Transgenerational Epigenetic Inheritance: Insights from Transgenic Mice
      • Introduction
      • Tei IN Classical Transgenes: Heritable Transcription Silencing
      • Potential Mechanisms of TEI at the Classical Transgenes
      • Insights from Inducible Mouse Models: Timing is Everything for Mitotic Inheritance, But Location is also Crucial for TEI
      • Conclusions and Future Perspectives
    • Chapter 9. Histone-Mediated Transgenerational Epigenetics
      • Introduction
      • Histones and Histone Modifications
      • Evidence that Histones are not Completely Erased During Gametogenesis
      • Transgenerational Changes of Histone Modifications in Different Experimental Models
      • Altered Histone Modifications in Human Genetic Diseases
      • Future Directions
    • Chapter 10. Heritable Generational Epigenetic Effects through RNA
      • Introduction
      • Transgenerational Inheritance Via the Gametes
      • Gametic RNA Populations
      • Small RNA Pathways
      • RNA-Guided Genome Rearrangements in Ciliates
      • RNA Transport in Plant Systems
      • Paramutation in Maize
      • RNA Transfer Via the Gametes in Arabidopsis Thaliana
      • Transgenerational Inheritance of RNAi in Caenorhabditis Elegans
      • The PIRNA Pathway, Transposon Silencing, and Hybrid Dysgenesis in Drosophila Melanogaster
      • Transgenerational Epigenetic Inheritance in Mammals
      • Transgenerational Epigenetic Inheritance in Humans
      • Conclusion
  • Section V. Model Organisms
    • Chapter 11. Animal Models of Transgenerational Epigenetic Effects
      • Introduction
      • Considerations for Designing and Interpreting Transgenerational Animal Studies
      • Naturally Occurring Epigenetic/Transgenerational Animal Models
      • Extrinsic/Environmental Factor Induction of Transgenerational Effects in Animal Models
      • Mechanisms Leading to Transgenerational Inheritance
      • Conclusions and Future Directions
    • Chapter 12. Plant Models of Transgenerational Epigenetic Inheritance
      • Introduction
      • DNA Methylation in Plants
      • Histone Modification in Plants
      • Transgenerational Inheritance of Epigenetic Marks
      • Inheritance of Epigenetic Variants
      • Stress-Induced Epigenetic Modifications
      • Transgenerational Defense
      • Paramutation
      • Conclusion and Perspective
    • Chapter 13. Transgenerational Hormonal Imprinting in the Unicellular Tetrahymena
      • Introduction
      • The Hormonal System of Tetrahymena
      • Hormonal Imprinting
      • Is Hormonal Imprinting Executed by Influencing DNA Methylation?
      • Imprinting of the Nuclear Envelope
      • Imprinter Molecules (Hormones)
      • The Role of Signaling Pathways and Related Factors in the Provocation of Imprinting
      • Cell Functions Influenced by Hormonal Imprinting
      • The Receptor Nature of Binding Sites Induced by Imprinting
      • Biology of the Hormonal Imprinting at a Unicellular Level
  • Section VI. Evolution of Transgenerational Epigenetics
    • Chapter 14. Evolutionary Perspectives on Transgenerational Epigenetics
      • Introduction
      • Epigenetic Inheritance and Evolution
      • Evolutionary Responses: Beyond the Breeder’s Equation
      • Evolution of Epigenetic Inheritance: Stability Versus Plasticity
      • Conclusions
    • Chapter 15. Inheritance of Epigenome Variants Across Generations and its Implications on the Emergence of Phenotypic Novelties During Evolution
      • Introduction
      • Transgenerational Epigenetics
      • Gene–Environment Interactions and Phenotypic Variation
      • Epigenetic Modifications of Chromatin
      • The Transgenerational Stability and Variability of Epialleles
      • Population Epigenetics
      • Current Challenges and Future Directions
      • Conclusion
      • Glossary
  • Section VII. Parental Epigenetic Inheritance
    • Chapter 16. Maternal Epigenetic Inheritance and Stress During Gestation: Focus on Brain and Behavioral Disorders
      • Introduction
      • Epigenetic Inheritance
      • Stress Effects
      • Behavioral Effects in Offspring Exposed to Prenatal Stress
      • HPA Axis Modifications in Offspring Exposed to Prenatal Stress
      • Neural Changes in Offspring Exposed to Prenatal Stress
      • Epigenetic Effects of Gestational Stress
      • Future Directions
      • Summary
    • Chapter 17. Paternal Epigenetic Inheritance
      • Introduction
      • Paternal Transgenerational Effects
      • Mechanisms of Paternal Transgenerational Effects
      • Issues and Future Directions
  • Section VIII. Environmental Epigenetic Effects on the Offspring
    • Chapter 18. Transgenerational Epigenetics of Endocrine-Disrupting Chemicals
      • Introduction
      • Endocrine-Disrupting Chemicals
      • Epigenetic Programming and the Developmental Origins of Health and Disease
      • Pathways to Epigenetic Alterations
      • Epigenetic Requirements to Produce Disease
      • A Potential Role for the Microbiome in Risk of Adverse Epigenetic Alterations
      • Multigenerational Versus Transgenerational Epigenetic Programming
      • The Genomic Reset Issue
      • Specific EDCs, EDC Mixtures, and Transgenerational Epigenetics
      • Conflicting Results
      • Implications and Conclusions
    • Chapter 19. Transgenerational Effects of Perinatal Hormonal Imprinting
      • Introduction
      • Perinatal Hormonal Imprinting
      • Transgenerational Hormonal Imprinting
      • Perinatal Hormonal Mis-Imprinting by Endocrine Disruptors and its Inheritance
      • Phytosteroids as False Imprinters
      • Late Imprinting
      • The Importance of Hormonal Imprinting and its Heredity
    • Chapter 20. Phenotypic and Epigenetic Inheritance Across Multiple Generations in Mammals Through the Female Line
      • Introduction: Early Environment, Epigenetics and Induced Phenotypic Traits
      • Models of Environmental Challenge and Implications for Transgenerational Inheritance
      • Passage of Induced Traits Between Generations: Evidence from Transient Environmental Challenge
      • Passage of Induced Traits between Generations: Evidence from Persistent Environmental Challenge
      • Models of Transgenerational Phenotypic and Epigenetic Variation
      • Conclusions
  • Section IX. Impact of Transgenerational Epigenetics on Disease
    • Chapter 21. Transgenerational Epigenetic Inheritance of Type 2 Diabetes
      • Introduction
      • Transgenerational Effects
      • Transgenerational Epigenetic Inheritance in Mammals
      • Transgenerational Inheritance of Diabetes in Humans
      • Transgenerational Inheritance of Diabetes in Animal Models
      • The Debate: Transgenerational Epigenetic Inheritance of Diabetes?
      • Concluding Remarks
    • Chapter 22. Epigenetic Transgenerational Inheritance of Reproductive Disease
      • Introduction
      • The Epigenetic Control of Genes by DNA Methylation
      • Epigenetic Effects on the Reproductive System
      • Questions and Perspectives
      • Conclusions
    • Chapter 23. Cardiovascular Disease and Transgenerational Epigenetic Effects
      • Introduction
      • Transgenerational Effects in CVD
      • Transgenerational Epigenetic Changes in CVD: Single-Generation Transmission
      • Epigenetic Changes and Atherosclerosis
      • Epigenetic Changes and Lipid Metabolism
      • Transgenerational Epigenetic Changes in CVD: Multiple-Generation Transmission
      • Conclusions
    • Chapter 24. Mental Disorders and Transgenerational Epigenetics
      • Introduction
      • Epigenetic Understanding of Congenital Mental Disorders
      • Role of Epigenetics IN Acquired Mental Disorders
      • Transgenerational Epigenetic Inheritance
      • Perspectives
  • Section X. Clinical Significance of Transgenerational Epigenetics
    • Chapter 25. Clinical Aspects of Transgenerational Epigenetics
      • Introduction
      • How can Epigenetics be Transgenerational?
      • Physiological Consequences of Transgenerational Epigenetics
      • Pathophysiological Consequences of Transgenerational Epigenetics
      • Research and Diagnostics
      • Therapy
      • Nutrition During Pregnancy
      • Epigenetic Changes Caused by Radiation and Toxic Substances
      • Conclusion
  • Section XI. Controversies and Debate of Generational Epigenetic Inheritance
    • Chapter 26. Transgenerational Epigenetics: Current Controversies and Debates
      • Introduction
      • Epigenetics and Behavioral Biology
      • Epigenotypes Versus Epiphenotypes (Molecular vs. Molar Epigenetics)
      • Context-Dependent VS. Germline-Dependent Epigenetic Modifications
      • Body Burdens Include our Personal Exposures, and Those Inherited from our Ancestors
      • The Fallacy of Ecologically Relevant Dosages
      • Experimental Simulation of Exposures in the Real World (Mixtures and Synergy)
      • Thresholds
      • Species, Sex, and Individual Differences
      • Conclusion
      • Glossary
  • Glossary
  • Index


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About the Editor

Trygve Tollefsbol

Professor of Biology, University of Alabama at Birmingham, Birmingham, AL. Dr. Tollefsbol is a Professor of Biology and a Senior Scientist in the Center for Aging, Comprehensive Cancer Center, Nutrition Obesity Research Center, and the Comprehensive Diabetes Center at the University of Alabama at Birmingham (UAB). He is Director of the UAB Cell Senescence Culture Facility which he established in 1999 and a Steering Committee Member of the UAB Center for Aging. Dr. Tollefsbol trained as a Postdoctoral Fellow and Assistant Research Professor with members of the National Academy of Science at Duke University and the University of North Carolina. He earned doctorates in molecular biology and osteopathic medicine from the University of North Texas Health Sciences Center and his bachelor’s degree in Biology from the University of Houston. He has received prior funding from the NIA, NCI, NHLBI, NIMH and other federal institutes as well as the Glenn Foundation for Medical Research, Susan G. Komen for the Cure, the American Federation for Aging Research (AFAR), and the American Institute for Cancer Research (AICR) among many other sources. The Glenn Foundation for Medical Research funding was unsolicited and was awarded to Dr. Tollefsbol for lifetime contributions to the field of aging. In 2006 Dr. Tollefsbol was selected and highlighted as part of the 25th anniversary of the AFAR for significant contributions to aging research. Dr. Tollefsbol’s research interests have covered a wide range of topics such as aging, epigenetics, nutrition, cancer, telomerase, and caloric restriction. Work from his laboratory has been featured in Women’s Health magazine, Shape magazine, and the AICR Newsletter and Dr. Tollefsbol has been a Scientist in the Spotlight in ScienceNow. Currently he serves as an Associate Editor for Frontiers in Epigenomics and is on the Editorial Boards of the international journals Open Longevity Science, Epigenetics of Diabetes and Obesity, Molecular Biotechnology and Clinical Epigenetics. He is also a contributing Editor of Lewin’s GENES X classic textbook. Over 25 of the publications from Dr. Tollefsbol’s laboratory have received national or international accolades such as best paper award, selection for press release by the journal editors and featured on the journal homepage. Dr. Tollefsbol has been invited to give presentations on his research in many countries including Germany, China, Italy, Switzerland, France and The Netherlands as well as at various leading institutions in the US such as Harvard Medical School, Tufts University and the University of California at San Francisco. His research has received considerable media attention both nationally and internationally through television, newspaper and radio venues and has been highlighted in eScience News and ScienceDaily. He has ten books which have been published or are in progress and a recent book on “Epigenetics of Aging” that Dr. Tollefsbol co-authored and edited was highlighted in Nature.

Affiliations and Expertise

Professor of Biology, University of Alabama at Birmingham, AL, USA


"This book is unique in its focus solely on this subject. This is an area destined to become extremely important in the practice of human and medical genetics. This book is without comparison. Score: 99 - 5 Stars", January 23, 2015

"...this seminal book on transgenerational epigenetics not only confronts these controversies, but also illuminates many other aspects of transgenerational epigenetics."--Anticancer Research, January 2015