Rousseaux / Khochbin Epigenetics and Human Reproduction

1. Auflage 2010
ISBN: 978-3-642-14773-9
Verlag: Springer
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 372 Seiten

Epigenetics is a rapidly expanding field in medical and biological research which concerns heritable traits that are not attributable to changes in the DNA sequence. Epigenetic mechanisms play key roles in many biological processes, and it has become clear that their disruption can gives rise to diverse pathologies in humans. Edited by preeminent experts, Sophie Rousseaux and Saadi Khochbin, this volume in the ‘Epigenetics and Human Health’ series discusses the role of epigenetics in human reproduction

Autoren/Hrsg.

Rousseaux, Sophie

Khochbin, Saadi

Inhaltsverzeichnis

1;Preface to the Series;6
2;Foreword;8
2.1;References;10
3;Contents;12
4;Contributors;14
5;Part I: Medical Aspects and Questions Raised on the Molecular Basis of Epigenome Involvement in Reproduction;18
5.1;Chapter 1: Potential Epigenetic Consequences Associated with Assisted Reproduction;19
5.1.1;1.1 Introduction;20
5.1.2;1.2 ARTs and the Timing of Epigenetic Events during Gametogenesis and Embryogenesis;20
5.1.2.1;1.2.1 Gamete Development;21
5.1.2.2;1.2.2 Preimplantation Embryo Development;22
5.1.3;1.3 Assisted Reproduction and Imprinting Disorders;22
5.1.4;1.4 Searching for Epigenetic Abnormalities in Children Conceived Using ARTs;24
5.1.5;1.5 Underlying Infertility as a Contributor to Imprinting Defects After ART;25
5.1.6;1.6 Techniques Used in ART and Imprinting Defects;27
5.1.7;1.7 Assisted Reproduction and Other Potential Epigenetic Effects;27
5.1.8;1.8 Lessons from Animal Models: Mimicking Techniques Used in Human-Assisted Reproduction;28
5.1.8.1;1.8.1 Superovulation and Gamete Manipulation;28
5.1.8.2;1.8.2 Embryo Culture;29
5.1.9;1.9 Future Directions;30
5.1.10;References;31
5.2;Chapter 2: Germ Cell Cancer, Testicular Dysgenesis Syndrome and Epigenetics;35
5.2.1;2.1 Introduction;36
5.2.2;2.2 Epigenetics in Testicular Development: From Specification of Primordial Gem Cells to Formation of the Gonads;36
5.2.3;2.3 TDS: A Collection of Reproductive Disorders with a Possible Common Pathogenesis;39
5.2.3.1;2.3.1 Testicular Cancer;39
5.2.3.2;2.3.2 Undescended Testis and Hypospadias;41
5.2.3.3;2.3.3 Impaired Spermatogenesis with Developmental Aetiology;41
5.2.4;2.4 Endocrine Disrupters and Their Possible Influence on Epigenetic Patterns;42
5.2.4.1;2.4.1 Evidence from Human Studies;42
5.2.4.2;2.4.2 Evidence from Studies in Animals;43
5.2.5;2.5 Epigenetics of Germ Cell Tumors and Testicular Dysgenesis;44
5.2.5.1;2.5.1 Chromatin Changes;44
5.2.5.2;2.5.2 Methylation Profiles of Specific Genes Important for Pluripotency and Tumorigenesis;46
5.2.5.3;2.5.3 X-Linked Genes and XIST Expression;47
5.2.5.4;2.5.4 Gene Imprinting;48
5.2.5.5;2.5.5 Possible Involvement of miRNAs in TGCTs and Neoplastic Transformation;50
5.2.6;2.6 Open Questions and Perspectives;51
5.2.7;References;52
5.3;Chapter 3: Medical Implications of Sperm Nuclear Quality;61
5.3.1;3.1 Fundamental Knowledge on Sperm Genome and Proteome/Epigenome Constitution;62
5.3.1.1;3.1.1 Changes in Sperm Nuclear Composition and Structure During Spermatogenesis;62
5.3.1.2;3.1.2 Sperm Cell Nuclear Proteome;64
5.3.1.3;3.1.3 Sperm Cell Epigenome;69
5.3.2;3.2 Approaches/Tests for Exploring Sperm Nuclear Quality in Human Infertility;72
5.3.2.1;3.2.1 Sperm DNA Quality and Integrity;72
5.3.2.2;3.2.2 Measurement of the Protamine Content in Infertile Patients;76
5.3.2.3;3.2.3 Correlation Between Protamines and Sperm DNA Integrity;79
5.3.3;3.3 Sperm Nuclear Quality and Outcome of ART;80
5.3.4;3.4 Present Limitations of Sperm Nuclear Quality Assessment and Open Questions;84
5.3.5;References;85
5.4;Chapter 4: Gene Expression/Phenotypic Abnormalities in Placental Tissues of Sheep Clones: Insurmountable Block in Cloning Progress?;100
5.4.1;4.1 Introduction;100
5.4.2;4.2 Abnormal Nuclear Reprogramming in Clones and Related Placental Phenotypes;102
5.4.3;4.3 Possible Directions to Improve SCNT;106
5.4.4;4.4 Concluding Remarks;108
5.4.5;References;109
6;Part II: Fundamental Aspects of Genome and Epigenome Reprogramming During Gametogenesis;112
6.1;Chapter 5: Epigenetic Reprogramming Associated with Primordial Germ Cell Development;113
6.1.1;5.1 Introduction;113
6.1.1.1;5.1.1 From Fertilization to the Specification of the New Germ Cell Lineage;114
6.1.2;5.2 A Brief Overview of the Epigenetic Reprogramming During PGC Development;116
6.1.3;5.3 The Cell Cycle State of PGCs;118
6.1.4;5.4 Genome-Wide DNA Demethylation in Migrating PGCs;119
6.1.5;5.5 Genome-Wide Demethylation of H3K9me2 in Migrating PGCs;120
6.1.6;5.6 Global Transcriptional Repression in Migrating PGCs;121
6.1.7;5.7 Genome-Wide Upregulation of H3K27me3 in Migrating PGCs;122
6.1.8;5.8 Arginine Methylation Mediated by Blimp1/Prmt5 Complex in Migrating PGCs;122
6.1.9;5.9 Potential Significance of Epigenetic Reprogramming in Migrating PGCs;123
6.1.10;5.10 Epigenetic Reprogramming of Imprinted Genes in Postmigrating PGCs;124
6.1.11;5.11 Modification of the Repetitive Elements in PGCs;125
6.1.12;5.12 Modification of the Specific Loci in PGCs;126
6.1.13;5.13 Conclusion;127
6.1.14;References;127
6.2;Chapter 6: Epigenetic Factors and Regulation of Meiotic Recombination in Mammals;132
6.2.1;6.1 Introduction;133
6.2.2;6.2 Outline of the Molecular Mechanism of Meiotic Recombination;134
6.2.3;6.3 How to Measure Recombination Activity in Mammals?;136
6.2.3.1;6.3.1 Pedigree Analysis;136
6.2.3.2;6.3.2 Sperm Typing;137
6.2.3.3;6.3.3 MLH1 Foci;137
6.2.3.4;6.3.4 Population Diversity Analysis;137
6.2.4;6.4 Indirect Evidence that Epigenetic Modifications Influence Recombination Activity in Mammals;138
6.2.4.1;6.4.1 Male Versus Female Recombination;138
6.2.4.1.1;6.4.1.1 Male and Female Genetic Maps;138
6.2.4.1.2;6.4.1.2 Recombination Activities in Minisatellites;142
6.2.4.1.3;6.4.1.3 Regions Subjected to Parental Imprinting;142
6.2.4.1.4;6.4.1.4 CO Frequency and Length of the Synaptonemal Complex;143
6.2.4.2;6.4.2 Interindividual Variations;143
6.2.4.2.1;6.4.2.1 Variations in Genome Wide CO Rates;144
6.2.4.2.2;6.4.2.2 Variations of Hotspot Activity in Humans;144
6.2.4.2.3;6.4.2.3 Variations of Hotspot Activity in Mice;146
6.2.5;6.5 Evidence for Epigenetic Modifications During Meiosis and Genes Known to Regulate such Modifications in Mammals;146
6.2.5.1;6.5.1 DNA Methylation;146
6.2.5.2;6.5.2 Histone Modifications;148
6.2.5.3;6.5.3 Histone Variants in Meiotic Prophase I (Fig.6.5b);153
6.2.5.3.1;6.5.3.1 The Specific Case of the XY Sex Body (Histone Modifications and Histone Variants);153
6.2.5.3.2;6.5.3.2 H2A and H2B Variants;153
6.2.5.3.2.1;Phosphorylation of H2AX;153
6.2.5.3.2.2;Testis-Specific Histone Variants TH2A and TH2B;154
6.2.5.3.3;6.5.3.3 H3 Variants;154
6.2.5.3.4;6.5.3.4 H1 Variants;155
6.2.5.4;6.5.4 Noncoding RNAs During Spermatogenesis;155
6.2.6;6.6 How Could It Work: Are Meiotic Recombination Initiation Sites Defined by a Specific Combination of DNA Sequence and Chromatin Features?;156
6.2.6.1;6.6.1 Methylation of DNA Inhibits the Formation of Crossovers;156
6.2.6.2;6.6.2 Sequence Features and Open Chromatin at Recombination Initiation Sites;157
6.2.6.3;6.6.3 A Model: Chromatin Writers and Readers as Major Determinants of Meiotic Recombination;159
6.2.7;6.7 Perspectives;161
6.2.8;References;162
6.3;Chapter 7: Meiotic Pairing of Homologous Chromosomes and Silencing of Heterologous Regions;170
6.3.1;7.1 Introduction;171
6.3.2;7.2 Evolution of Sex Chromosomes;172
6.3.3;7.3 Homologous Chromosome Pairing in Meiotic Prophase;174
6.3.3.1;7.3.1 Bouquet Formation;174
6.3.3.2;7.3.2 Meiotic DNA Double-Strand Break Formation;174
6.3.3.3;7.3.3 Synaptonemal Complex Formation;175
6.3.3.4;7.3.4 Meiotic DNA Double-Strand Break Repair;176
6.3.3.5;7.3.5 Meiotic Checkpoint Regulation During Male Meiotic Prophase;177
6.3.4;7.4 Sex Chromosomal Behavior During Mammalian Spermatogenesis;178
6.3.4.1;7.4.1 Pairing of X and Y in Meiotic Prophase;178
6.3.4.2;7.4.2 Meiotic DSB Repair at X and Y;181
6.3.4.3;7.4.3 Meiotic Sex Chromosome Inactivation;182
6.3.4.4;7.4.4 Meiotic Silencing of Unsynapsed Chromatin;184
6.3.4.5;7.4.5 Postmeiotic Silencing of Sex Chromosomes;186
6.3.5;7.5 Silencing of X and Y During Spermatogenesis and X Chromosome Inactivation in Female Somatic Cells Are Independent Mechanism;187
6.3.6;7.6 Meiotic Silencing of Sex Chromosomes in a Species with Female Heterogamety;188
6.3.7;7.7 What Drives Meiotic Silencing in Mouse and Man?;189
6.3.8;7.8 Clinical Relevance of Meiotic Silencing;192
6.3.9;References;193
6.4;Chapter 8: Histone Variants during Gametogenesis and Early Development;200
6.4.1;8.1 Introduction;201
6.4.2;8.2 Meiotic Chromatin;205
6.4.2.1;8.2.1 Histone Variants;205
6.4.2.2;8.2.2 More Sex Chromosome Aspects;208
6.4.3;8.3 Spermiogenesis and Mature Sperm;209
6.4.4;8.4 Significance for Nucleosomes, Histone Variants for Embryonic Development;213
6.4.5;8.5 Male Transgenerational Inheritance and Effects;215
6.4.6;8.6 Future Directions;217
6.4.7;References;218
6.5;Chapter 9: Genome Organization by Vertebrate Sperm Nuclear Basic Proteins (SNBPs);226
6.5.1;9.1 Packing the Paternal Genome with Small and Large Sperm-Specific Nuclear Basic Proteins;227
6.5.2;9.2 Packing Sperm Chromatin. The Roles of Acetylation and Phosphorylation;228
6.5.3;9.3 Mammalian Transition Proteins;232
6.5.4;9.4 Protamines. Packing Chromatin in an Orderly Fashion;235
6.5.5;9.5 Mammalian SNBPs and Infertility. The Intriguing Role of TPs and Protamines in DNA Integrity;236
6.5.6;9.6 Concluding Remarks;237
6.5.7;References;238
6.6;Chapter 10: Epigenetics in Male Reproduction: A Practical Introduction to the Informatics of Next Generation Sequencing;244
6.6.1;10.1 Introduction;245
6.6.1.1;10.1.1 Heritability, Disease, and Model Systems;247
6.6.2;10.2 Approaches and Online Resources for Epigenetic Investigation;248
6.6.2.1;10.2.1 DNA Methylation and Imprinting;248
6.6.2.2;10.2.2 Histone Substitution and Higher Order Chromatin Structure;249
6.6.2.3;10.2.3 Histone Modification;249
6.6.2.4;10.2.4 Transcriptional Modulation by Small RNAs;250
6.6.3;10.3 Deep Sequencing Approaches for Epigenetic Investigation;251
6.6.3.1;10.3.1 Scale of Sequencing Experiments;251
6.6.3.2;10.3.2 NGS Technologies Overview;252
6.6.3.3;10.3.3 Principles of NGS Sequencing;253
6.6.3.4;10.3.4 Illumina GAII and Roche 454 FLX;253
6.6.3.5;10.3.5 Applications of Deep Sequencing;255
6.6.3.6;10.3.6 Types of Sequencing;255
6.6.3.7;10.3.7 Sequencing Depth;256
6.6.3.8;10.3.8 Alignment Tools;258
6.6.3.9;10.3.9 Identification of Small RNAs;260
6.6.3.10;10.3.10 Sources of Error in Alignment and Interpretation;261
6.6.3.11;10.3.11 Peak Detection;262
6.6.3.12;10.3.12 Estimating False Discovery;264
6.6.3.13;10.3.13 Data Visualization;264
6.6.3.14;10.3.14 Sequencing Systems and Epigenetics;265
6.6.4;Suggested Reading and Environmental Epigenetic Effects;266
6.6.5;References;267
7;Part III: Re-organization of Nuclear Compartments During Gametogenesis ;272
7.1;Chapter 11: Organization of Chromosomes During Spermatogenesis and in Mature Sperm;273
7.1.1;11.1 Introduction;274
7.1.2;11.2 Chromosome Organization in Somatic Interphase: Brief Outlook;274
7.1.3;11.3 From Spermatogonia to Early Spermatids;275
7.1.3.1;11.3.1 Proliferation;275
7.1.3.2;11.3.2 Stages of Meiosis I;276
7.1.3.2.1;11.3.2.1 Movements and Interactions of Telomeres and Centromeres During Prophase I of Meiosis;277
7.1.3.2.2;11.3.2.2 Proteins Participating in Telomere Movement;277
7.1.3.3;11.3.3 Sex Chromosomes;278
7.1.4;11.4 Spermiogenesis;279
7.1.5;11.5 Spermatozoa;279
7.1.6;11.6 Chromosome Positioning;281
7.1.7;11.7 Tripartite Organization of Human Sperm Chromatin;284
7.1.8;11.8 Concluding Remarks;285
7.1.9;References;286
7.2;Chapter 12: Nuclear Lamins in Mammalian Spermatogenesis;290
7.2.1;12.1 The Nuclear Lamina;290
7.2.2;12.2 Mammalian Germ Line-Specific Lamin Isoforms;292
7.2.3;12.3 Nuclear Lamins in Mammalian Meiosis;293
7.2.4;12.4 Nuclear Lamins in Mammalian Spermiogenesis;295
7.2.5;12.5 Nuclear Lamins in Spermatogenesis of Nonmammalian Vertebrates;297
7.2.6;12.6 Outlook;297
7.2.7;References;297
8;Part IV: Fundamental Aspects of Gene Expression Regulation During Gametogenesis;300
8.1;Chapter 13: Specific Transcription Regulatory Mechanisms of Male Germ Cells;301
8.1.1;13.1 Introduction;301
8.1.1.1;13.1.1 Transcriptional Regulation in Male Germ Cells of Drosophila Melanogaster;302
8.1.1.2;13.1.2 Genes Encoding Paralogs of Subunits of the TFIID Complex Are Essential for Normal Spermatogenesis in Mammals;306
8.1.1.2.1;13.1.2.1 TBP-Related Factors;306
8.1.1.2.2;13.1.2.2 Genes Encoding TAF Paralogs;308
8.1.1.3;13.1.3 CREM, ACT, and KIF17b Cooperate in an Integrated Regulatory Mechanism Required for Spermatogenesis in Mouse and Humans;311
8.1.2;13.2 What Have Mouse Knockout Studies Told Us About the Physiopathology of Human Infertility?;313
8.1.3;References;314
8.2;Chapter 14: The Chromatoid Body: A Specialized RNA Granule of Male Germ Cells;320
8.2.1;14.1 Introduction;320
8.2.1.1;14.1.1 RNA Processing in Male Germ Cells;321
8.2.1.2;14.1.2 A Highly Specialized RNA Granule;322
8.2.1.3;14.1.3 Unique Features of the CB;323
8.2.1.4;14.1.4 Components of the Chromatoid Body;324
8.2.1.5;14.1.5 The Critical Roles of MIWI and PIWI;325
8.2.1.6;14.1.6 Dynamic Movements of the CB;329
8.2.1.7;14.1.7 Regulation by Critical Interactions;330
8.2.1.8;14.1.8 RNA Granules in Somatic Versus Germ Cells;332
8.2.2;References;333
8.3;Chapter 15: Sperm RNA: Reading the Hidden Message;338
8.3.1;15.1 Introduction;339
8.3.2;15.2 Gene Expression Studies in Mature Spermatozoa: Historical Aspects;341
8.3.3;15.3 Gene Expression Studies in Mature Spermatozoa: In Relation to Sperm RNA Carriage;344
8.3.4;15.4 Sperm RNA as a Diagnostic Resource;347
8.3.5;15.5 Functions for Sperm RNA;350
8.3.6;15.6 Is the Spermatozoon Nucleus More Active Than We Think?;351
8.3.7;15.7 Conclusions;354
8.3.8;References;355
9;Glossary;363
10;Index;376