Early Life Origins of Human Health and Disease

Contents......Page 5
Preface......Page 7
Abbreviations......Page 8
Issue 1: The Need for a Conceptual Framework – Moving beyond Phenomenology......Page 10
Issue 2: The Place of Development in Biological Thought......Page 13
Issue 3: The Need for a Mechanism......Page 15
Issue 4: The Geopolitical Implications of DOHaD......Page 16
References......Page 17
Phenotype Induction and Gene Transcription......Page 20
Epigenetic Mechanisms and Regulation of Transcription......Page 21
Early Life Environment and Epigenetic Gene Regulation......Page 23
Maternal Protein Restriction and Altered Epigenetic Gene Regulation......Page 24
Transgenerational Transmission of Altered Epigenetic Gene Regulation......Page 26
Observations in Humans......Page 27
References......Page 28
The Economics of Developmental Origins of Health and Disease: Modelling the Benefit of a Healthy Start to Life......Page 30
Targeting the Life Course......Page 31
Global Applicability......Page 33
Valuing Health......Page 34
Challenges Ahead......Page 35
References......Page 36
Nutritional Interventions in Mothers to Improve the Health of the Offspring – Are We Ready?......Page 38
Evidence Linking Maternal Nutrition in Pregnancy to Long-Term Outcomes in the Offspring......Page 39
Importance of Pre-Pregnant/Peri-Conceptional Nutrition......Page 44
Recent Intervention Trials in Human Pregnancy......Page 45
Nutritional Interventions – Are We Ready?......Page 46
References......Page 47
Developmental Origins of Health and Disease: The Importance of Environmental Exposures......Page 51
Prenatal Exposure to Diethylstilbestrol: Proof of Principle......Page 54
Other Selected Examples of Adult Diseases with Developmental Origins......Page 55
Conclusions......Page 58
References......Page 59
Developmental Origins of Health and Disease across Generations – Theory, Observation, Experiment......Page 61
Early Animal Experiments Showing Intergenerational Influences......Page 62
The Intergenerational Transmission of Obesity and Diabetes......Page 63
Towards Establishing Effects in Humans......Page 64
Mechanisms of Intergenerational Influences......Page 66
Theoretical Perspectives......Page 68
References......Page 70
Model 1: Oxygen and Embryo Developmental Potential......Page 74
Model 2: Maternal Diet and Embryo Developmental Potential......Page 77
Model 3: B Vitamins, DNA Methylation Programming and Embryo Developmental Potential......Page 80
Acknowledgements......Page 82
References......Page 84
Fetal Growth and Lung Development......Page 87
Postnatal Nutrition, Growth and Lung Development......Page 89
The Effects of Maternal Smoking on Lung Development......Page 90
Preterm Birth, Lung Development and Later Lung Function......Page 91
Conclusions......Page 95
References......Page 96
Fetal Hypothalamic-Pituitary-Adrenal Maturation......Page 98
Hypothalamic-Pituitary-Adrenal Activation, Placental CRH and Urocortins......Page 100
Interrelationships between Nutrition, Hypothalamic-Pituitary-Adrenal Function and Preterm Birth......Page 103
Effects of Exogenous Glucocorticoid on Fetal Development and Programming......Page 105
References......Page 107
Developmental Origins of Musculoskeletal Disease......Page 109
Epidemiological Studies......Page 110
Physiological Studies......Page 111
Maternal Nutrition, Lifestyle and Neonatal Bone Mineral......Page 112
Childhood Growth and Hip Fracture......Page 113
Developmental Plasticity and Osteoporosis......Page 114
Sarcopoenia......Page 115
Nutrition......Page 116
Conclusion......Page 118
References......Page 119
Developmental Origins of Female Reproductive Health......Page 122
Mechanistic Factors Underlying the Programming of Reproductive Health......Page 125
Conclusion......Page 128
References......Page 129
Immune Pathways Involved in the Development of Tolerance......Page 132
Evidence that Early Defects in Immune Pathways Are Associated with Subsequent Allergic Disease......Page 133
Genetic Factors That Contribute to Successful Tolerance......Page 134
Evidence that Early Immune Pathways Can Be Modified by Environmental Exposures......Page 135
Conclusion......Page 138
References......Page 139
Critical Periods of Vulnerability......Page 142
Permanent Effects on Structure and Function......Page 145
Conclusions......Page 148
References......Page 149
Intrauterine Growth Restriction and Programmed Obesity......Page 151
Physiological Systems That Regulate Appetite......Page 154
Development of Physiologic Systems Regulating Appetite......Page 160
Mechanisms of Perinatal Appetite Programming......Page 162
References......Page 165
Fetal Programming of Type 2 Diabetes......Page 173
Animal Models......Page 174
Mechanisms in Humans......Page 178
References......Page 179
Neonatal Exendin-4 Prevents the Development of Diabetes Mellitus in the IUGR Rat......Page 183
Chromatin Remodeling in the IUGR Rat......Page 185
IUGR Is Associated with Progressive Epigenetic Modifications That Silence Pdx1......Page 186
Conclusions......Page 189
References......Page 190
Prenatal Risk Factors for Breast Cancer and Clues to the Underlying Biological Mechanisms from Animal and Human Studies......Page 193
Prenatal Risk Factors for Breast Cancer – The Epidemiological Evidence......Page 194
Animal Studies Using Diethylstilbestrol as a Model for in utero Estrogen Exposure......Page 196
The Consistency of Human Biological Evidence with Current Hypotheses for Hormonal Mechanisms Underlying the Associations of Prenatal Risk Factors for Breast Cancer......Page 199
References......Page 200
The Offspring of Women with Severe Mental Disorder......Page 202
Study 1. The Neurodevelopmental Hypothesis and Schizophrenia: Evidence from the Western Australian Study of Women with Severe Mental Illness......Page 203
Study 2. Adverse Pregnancy Outcome in Schizophrenia: Maternal and Paternal Influences......Page 207
Study 3. Linking Schizophrenia Epidemiology and Developmental Neurobiology: The Impact of Low Prenatal Vitamin D on Brain Development......Page 209
Conclusion......Page 211
References......Page 212
Evidence of Gene-Environment Interactions Underlying Developmental Origins of Health and Disease......Page 214
Interaction between Variations in Genetic Sequence, the Environment and Developmental Origins of Health and Disease......Page 215
Interaction between the Environment, the Epigenome and Developmental Origins of Health and Disease......Page 216
Approaches and Challenges for Investigating Gene-Environment Interactions and Developmental Origins of Health and Disease......Page 218
Conclusions......Page 223
References......Page 224
Author Index......Page 227
Subject Index......Page 228