Genetic Damage in Human Spermatozoa (Advances in Experimental Medicine and Biology, 1166)

"There are several types of damage that can be found in the male gamete. This book covers the genetic damage in spermatozoa that can originate during spermatogenesis, or during transit in both male and female genital tracts. Damage can also be due to ageing, environmental or iatrogenic conditions, as well as to the protocols to cryopreserve and to select spermatozoa in assisted reproduction techniques. The purpose of this book is to provide a comprehensive resource for all possible DNA damages in sperm, the relation to fertility and infertility, and possible transgenerational heritable effects"--Publisher's description Preface 7 Contents 8 Contributors 10 1: Genetic Factors Affecting Sperm Chromatin Structure 13 Introduction 13 Regulation of Spermatid Gene Expression 14 Importance of the Nuclear Envelope 24 Remodeling of Chromatin Structure During Spermatid Differentiation 25 Histone Posttranslational Modifications and Enzymes 25 Histone Variants and Transition Proteins 27 Chaperones and Readers 29 Regulation of DNA Breaks 31 Other Genes Involved in Sperm Chromatin Structure 31 Protamines 32 Conclusion 33 References 33 2: Age-Dependent De Novo Mutations During Spermatogenesis and Their Consequences 41 Introduction 41 De Novo Chromosomal Anomalies During Spermatogenesis 42 Aneuploidies 43 Structural Aberrations 44 Y-Chromosome Rearrangements: The AZF Region Deletions/Duplications 45 De Novo Point Mutation Rate During Spermatogenesis 49 Paternal Age Effect Mutations 49 Consequences of PAE Mutations in the Offspring 50 Conclusions 53 References 54 3: The Sperm Epigenome: Implications for Assisted Reproductive Technologies 59 Introduction 59 The Sperm Epigenome: Protamination and Histone Modifications 60 The Sperm Epigenome: DNA Methylation 62 The Sperm Epigenome: Small, Noncoding RNAs 63 Using the Sperm Epigenome to Predict Fertility or ART Outcome 64 Conclusions 65 References 66 4: Epigenetic Transgenerational Inheritance 69 Layers of Epigenetic Information in Sperm 70 DNA Methylation 70 Sperm Chromatin 70 Noncoding RNAs 71 An Overview into the Concept of Transgenerational Inheritance 72 Environmental Factors Affect the Human Sperm Epigenome 73 Age 74 Obesity 74 Endocrine Disruptors 75 Diet 75 Metabolic Disorders: Diabetes 76 Chemotherapy 76 Alcohol 76 Smoking 76 Epigenetic Mechanisms Are Strong Candidates for Transferring Paternal Environmental Information 77 Sperm Epimutations Affect Embryo Development 77 Sperm Epimutations Affect the Health of the Exposed Men and Their Offspring 77 Intergenerational Inheritance 80 Transgenerational Inheritance 80 Is Multigenerational Disease Prevention a New Paradigm? 81 Concluding Remarks 81 References 82 5: Sperm DNA Fragmentation: Mechanisms of Origin 87 Introduction 87 Factors Inducing sDF 88 Mechanisms Inducing sDF 90 References 93 6: Sperm DNA Fragmentation: Consequences for Reproduction 98 Introduction 98 Methods of Sperm DNA Fragmentation Analysis 99 Comet Assay 99 Terminal Deoxynucleotidyl Transferase-Mediated dUTP Nick-End Labeling Assay 101 In Situ Nick Translation 101 Sperm Chromatin Structure Assay 102 Sperm Chromatin Dispersion Assay 103 Consequence of Sperm DNA Fragmentation on Male Reproductive Health 103 Systematic Analysis of the Consequences of Sperm DNA Fragmentation on Assisted Reproduction Technologies 104 Effect of Sperm DNA Damage on In Vitro Fertilization Rates 104 Effect of Sperm DNA Damage on Embryo Development 108 Effect of Sperm DNA Damage on ART Success 108 Association of Sperm DNA Damage with Pregnancy Loss 109 Effect of Sperm DNA Damage with Intrauterine Insemination Success 109 Sperm DNA Fragmentation as a Biomarker 110 Conclusion 110 References 111 7: Oxidative Damage to Sperm DNA: Attack and Defense 117 Why Spermatozoa DNA Is Susceptible to Oxidative Damage? 118 Where Are Sperm Cells at Risk of DNA Oxidative Damage? 118 Sperm Nuclear Oxidative Damage and Its Developmental Impacts (Putative Mutational Risks and Transgenerational Effects) 119 Sperm Nuclear and DNA Damage 119 Oxidative Alteration of the Sperm Nucleus and its Possible Consequences on Epigenetic Information 122 Oxidation of Nuclear Proteins 122 Oxidation of Methylated Cytosine Residues 122 Oxidation of Sperm-Associated RNAs 122 Endogenous and Exogenous Defense of Spermatozoa Against Oxidative DNA Damage 123 Conclusion 125 References 125 8: Interventions to Prevent Sperm DNA Damage Effects on Reproduction 128 Introduction 128 Clinical Recommendations for Sperm DNA Damage Testing 129 Interventions to Decrease Sperm DNA Fragmentation 130 Varicocele Repair 130 Changes in Lifestyle 139 Environment and Smoking 139 Diet 139 Obesity 140 Antioxidants 141 Treatment of Male Genital Tract Infection 143 Treatment of Comorbidities (Thyroid Diseases, Diabetes) 144 Empirical Medical Treatment 145 Avoid Late Fatherhood 146 Use of Testicular Sperm in Preference over Ejaculated Sperm for ICSI 146 Proposed Algorithm for SDF Testing and Use of Testicular Sperm for ICSI in Non-azoospermic Men with High SDF in the Semen 149 Conclusions 149 References 151 9: Cryopreservation of Sperm: Effects on Chromatin and Strategies to Prevent Them 158 Sperm Cryopreservation 159 Sperm Cryobiology 159 Cryopreservation Methods 161 Effect of Cryopreservation on DNA Integrity 162 Strategies to Prevent Cryopreservation Injuries 165 Enzymatic Antioxidants 167 Catalase 167 Superoxide Dismutase 167 Glutathione 167 Non-enzymatic Antioxidants 168 Vitamin E (a-Tocopherol/Trolox) 168 Vitamin C 168 L-Carnitine 169 L-Cysteine 169 Melatonin 169 Quercetin and Resveratrol 170 Natural Extracts (Opuntia ficus-indica and Genistein) 171 References 171 10: Effect on Sperm DNA Quality Following Sperm Selection for ART: New Insights 177 Sperm Selection: Methods Currently in Use 177 Advanced Methods for Sperm Selection 179 Sperm Surface Charge for Sperm Selection 179 Sperm Selection by Hyaluronic Acid Binding 181 Intracytoplasmic Morphologically Selected Sperm Injection (IMSI) 183 Magnetic-Activated Cell Sorting (MACS) 185 Sperm Head’s Birefringence 186 Emerging Methods for Sperm Selection 187 Microfluidics 187 Synthetic Peptides 188 Raman Spectroscopy 188 Conclusions 190 References 191 11: Sperm DNA Damage in Cancer Patients 196 Introduction 197 Impact of Cancer on Sperm 197 Impact of Cancer Treatment on Sperm 198 Radiotherapy 198 Chemotherapy 199 Impact on Fertility and the Health of Progeny 202 Fertility Preservation Strategies 203 References 205 Index 211 Front Matter ....Pages i-xiii Genetic Factors Affecting Sperm Chromatin Structure (Mélina Blanco, Julie Cocquet)....Pages 1-28 Age-Dependent De Novo Mutations During Spermatogenesis and Their Consequences (Francesca Cioppi, Elena Casamonti, Csilla Krausz)....Pages 29-46 The Sperm Epigenome: Implications for Assisted Reproductive Technologies (Douglas T. Carrell)....Pages 47-56 Epigenetic Transgenerational Inheritance (Joan Blanco Rodríguez, Cristina Camprubí Sánchez)....Pages 57-74 Sperm DNA Fragmentation: Mechanisms of Origin (Monica Muratori, Sara Marchiani, Lara Tamburrino, Elisabetta Baldi)....Pages 75-85 Sperm DNA Fragmentation: Consequences for Reproduction (Luke Simon, Benjamin Emery, Douglas T. Carrell)....Pages 87-105 Oxidative Damage to Sperm DNA: Attack and Defense (Joel R. Drevet, R. J. Aitken)....Pages 107-117 Interventions to Prevent Sperm DNA Damage Effects on Reproduction (Sandro C. Esteves)....Pages 119-148 Cryopreservation of Sperm: Effects on Chromatin and Strategies to Prevent Them (Donatella Paoli, Marianna Pelloni, Andrea Lenzi, Francesco Lombardo)....Pages 149-167 Effect on Sperm DNA Quality Following Sperm Selection for ART: New Insights (Nicoletta Tarozzi, Marco Nadalini, Andrea Borini)....Pages 169-187 Sperm DNA Damage in Cancer Patients (Hermance Beaud, Amelie R. Tremblay, Peter T. K. Chan, Geraldine Delbes)....Pages 189-203 Back Matter ....Pages 205-210 "There are several types of damage that can be found in the male gamete. This book covers the genetic damage in spermatozoa that can originate during spermatogenesis, or during transit in both male and female genital tracts. Damage can also be due to ageing, environmental or iatrogenic conditions, as well as to the protocols to cryopreserve and to select spermatozoa in assisted reproduction techniques. The purpose of this book is to provide a comprehensive resource for all possible DNA damages in sperm, the relation to fertility and infertility, and possible transgenerational heritable effects." - Prové de l'editor