Cell Signaling During Mammalian Early Embryo Development (eBook)

Henry Leese, PhD, is a Professor of Biology at Hull York Medical School and the founding Editor-in-Chief of Human Fertility. Daniel  Brison, PhD, is Honorary Professor of Clinical Embryology and Stem Cell Biology; Scientific Director of the Department of Reproductive Medicine; and Co-Director NW Embryonic Stem Cell Centre (NWESCC) at Central Manchester University Hospitals NHS Foundation Trust at St. Mary’s Hospital.

Preface 6
Contents 10
Contributors 11
Chapter-1 13
Cell Signalling During Blastocyst Morphogenesis 13
1.1 Introduction 13
1.2 Intrinsic Signals Regulating Blastocyst Morphogenesis 14
1.2.1 Cell Signalling at Fertilisation and Activation of the Development Programme 15
1.2.2 Cell Signalling at Compaction 15
1.2.3 Cell Signalling and Blastocyst Formation 17
1.2.4 Cell Signalling and the Stabilisation of Emergent Cell Lineages 18
1.3 Extrinsic Signalling Pathways 19
1.3.1 Insulin and Amino Acid Signalling—The mTORC Signalling Network 20
1.3.2 Energy Homeostasis—The AMPK Signalling Network 22
1.3.3 Lipid Metabolism and Fatty Acid Signalling 23
1.3.4 The Role of Methyl Group Availability 25
1.4 Conclusions 26
References 27
Chapter-2 34
Amino Acids and Conceptus Development During the Peri-Implantation Period of Pregnancy 34
2.1 Introduction 35
2.2 Leucine, Arginine and Glutamine 38
2.3 MechanisticTarget of Rapamycin (MTOR) 39
2.4 Nitric Oxide and Trophoblast Motility 40
2.5 Polyamines and Trophoblast Motility 41
2.6 Amino Acids in Uterine Flushings of Ewes and Gilts during the Peri-Implantation Period of Pregnancy 41
2.7 Nutrient Transporters in Uterine Epithelia and Conceptus Trophectoderm (see Table 2.5) 47
2.8 Expression of Components of the MTOR Cell Signaling Pathway in Ovine Conceptus Trophectoderm 49
2.9 Amino Acids Stimulate MTOR Cell Signaling 50
2.10 Beneficial Effects of Dietary Arginine Supplementation on Embryonic/Fetal Survival and Growth in Mammals 52
2.11 Summary 55
References 56
Chapter-3 64
The Role of Hexosamine Biosynthesis and Signaling in Early Development 64
3.1 The Embryo and its Environment 65
3.2 A Role for Glucose in Early Development? 66
3.3 Glucose Primes Embryos to Adapt to Their Environment 67
3.4 Hexosamine Biosynthesis: An Embryonic Nutrient-Sensing Pathway 68
3.5 The Response Path: N-Linked Vs. O-Linked Glycosylation? 70
3.6 Hexosamine Signalling: A Nutrient Response Pathway 71
3.6.1 The Enzymes 71
3.6.2 The Targets 72
3.7 O-GlcNAcylation in Development 73
3.8 The HSP: Sensor of an Adverse Environment? 74
3.9 Perturbed O-GlcNAcylation and Embryo Development 75
3.9.1 Embryotoxic Effects of Hyperglycemia and O-GlcNAcylation 76
3.9.2 Glucosamine as a Hyperglycemic Mimetic 77
3.9.3 Periconceptional HSP Pertubation and Postnatal Outcomes 78
3.10 Nutrient Stress, Embryonic Programming and O-Linked Glycosylation 79
3.11 What Makes the Early Embryo More Susceptible? 81
3.12 Conclusion 81
References 82
Chapter-4 88
Molecular Biology of the Stress Response in the Early Embryo and its Stem Cells 88
4.1 Introduction 90
4.2 Early events in Embryogenesis Balancing Anabolism and Stress During Early Embryonic Programming 92
4.2.1 Defining Stress and Categorizing Classes of Stress by the Transcription Factors in the Survival Responses of Somatic Cells, Stem Cells and Embryos 92
4.2.2 Integrating Maternal Nutritional/energy Status to Enable Peri-Implantation Embryogenesis to use Energy for Normal or Stressed Development 95
4.2.3 Stress During IVF/ART 101
4.2.4 Using Stress Responses to Optimize IVF 106
4.2.5 Insights from Knockouts of Genes that Regulate the Stress Response 108
4.2.6 Stress Enzymes in the Survival Response of Stem Cells and Embryos 113
4.2.7 Summary of the Homeostatic Stress Response Mechanism 116
4.3 Molecular Biology of the Stress Response in the Early Embryo and its Stem Cells the Organismal Survival Response Through Stress-Induced Differentiation at Higher Stress Exposures 116
4.3.1 The Role of Stress Enzymes in the Organismal Stress Response of Induced Differentiation of Stem Cells 120
4.3.2 The Difference Between all Stressors Compared with Hypoxic Stress Hypoxic Stress Induces Differentiation but Resulting Cells Tend to Remain more in Warburg Metabolism due to Hypoxia with O2?< ?2?% and Cannot Support the most Energy-Requiring Differen
4.4 Summary, Significance and Future Studies 127
References 130
Chapter-5 140
Survival Signalling in the Preimplantation Embryo 140
5.1 Introduction 141
5.2 Embryotrophic Ligands 141
5.3 Autocrine Ligands 142
5.4 Signal Transduction via PI3K 144
5.5 Downstream Responses to PIP3 147
5.6 AKT 148
5.7 PI3K-Dependent Calcium Signalling 149
5.8 Other PI3K-Mediated Survival Signalling Events 152
5.9 Survival Signalling Induces Latency of TRP53 153
5.10 Conclusion 155
References 155
Chapter-6 161
Intracellular Ca2+ Signaling and Preimplantation Development 161
6.1 Cellular Regulation of Cytoplasmic Ca2+ Concentrations 162
6.2 Intracellular Ca2+ Signaling During Fertilization 164
6.3 Regulation of Cleavage Stage Development by Intracellular Ca2+ 166
6.4 Regulation of Blastocyst Formation by Intracellular Ca2+ 168
6.5 Regulation of Trophoblast Adhesion by Intracellular Ca2+ 169
6.6 Regulation of Trophoblast Invasion by Intracellular Ca2+ 172
6.7 Conclusions and Speculation 174
References 176
Chapter-7 182
Female Tract Cytokines and Developmental Programming in Embryos 182
7.1 Introduction 183
7.2 Cytokines and Cell Communication 183
7.3 Cytokine Synthesis in the Oviduct and Uterus 185
7.3.1 Cytokine Production by Endometrial and Oviductal Epithelial Cells 185
7.3.2 Cytokine Production by Endometrial and Oviductal Leukocytes 187
7.4 Cytokine Regulation of Embryo Development 188
7.4.1 Endogenous Embryo-derived Growth and Survival Factors 188
7.4.2 Maternal Tract Cytokine—Embryo Communication 190
7.5 Cytokine Receptor Signal Transduction in Pre-Implantation Embryos 191
7.5.1 Phosphatidylinositol-3 kinase (PI3K)/Protein Kinase B (AKT) Pathway 193
7.5.2 Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) Pathway 193
7.5.3 Mitogen-Activated Protein Kinase (MAPK) Pathway 194
7.6 Cytokines Promoting Pre-Implantation Embryo Development 195
7.6.1 Granulocyte-Macrophage Colony-stimulating Factor (GM-CSF) 195
7.6.2 Colony Stimulating Factor-1 and Stem Cell Factor 197
7.6.3 Heparin-Binding EGF-like Growth Factor (HB-EGF) 198
7.6.4 Leukaemia Inhibitory Factor (LIF) 199
7.6.5 Insulin-Like Growth Factor I and II (IGFI and IGFII) 200
7.7 Cytokines Inhibiting Pre-Implantation Embryo Development 201
7.7.1 Tumour Necrosis Factor Alpha (TNF) 201
7.7.2 Interferon Gamma (IFN?) 202
7.7.3 Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) 202
7.8 Maternal Tract Cytokines and Developmental Competence 202
7.8.1 Cytokines and Embryo Programming 203
7.8.2 Cytokine Regulation of Embryo Sensing and Adaptation 204
7.8.3 Cytokines and Maternal Tract Quality Control 205
7.8.4 Cytokines as Mediators of Paternal Influence on Embryo Survival and Programming 206
7.9 Use of Cytokines in Assisted Reproductive Technology 207
7.9.1 GM-CSF Utility in IVF Embryo Culture Media 207
7.10 Conclusions 209
References 211
Index 223