Immune Infertility (eBook)

The Impact of Immune Reactions on Human Infertility

Walter K.H. Krause, Rajesh K. Naz (Herausgeber)

eBook Download: PDF

2009 | 2009
XI, 236 Seiten
Springer Berlin (Verlag)
978-3-642-01379-9 (ISBN)

Infos

Infertility is defned as the inability to conceive after having unprotected intercourse for a year. Infertility is increasing worldwide and has various causes both in the male and the female partner. Immune reactions to sperm can contribute up to 2-30% of infertility. The sperm has both autoantigenic as well as isoantigenic potential, and is thus capable of p- ducing antisperm antibodies (ASAs) and sperm-reactive T cells in both infertile men and women. Also, over 75% vasectomized men produce autoantibodies to sperm that can cause a problem in regaining fertility even after successful re-anastomosis in vasovasostomy. Early claims regarding the incidence and involvement of ASAs in involuntary human infertility were probably overemphasized because of unreliable techniques and naivety concerning the complexity of the immune response and antigenic nature of the sperm cell. These factors, the lack of well-designed and controlled experimental studies, and the dearth of effective therapeutic modalities resulted in the confusion of the occurrence and importance of ASAs in human infertility. Consequently, evaluation of infertile couples for ASAs and their possible role in infertility was not considered a signifcant proposition. The development of more accurate assays and the discovery of mucosal immunity capable of responses independent of systemic immunity have caused inclusion of sperm cells and genital tract secretions in the analysis of ASAs.

Inhalt

Preface 5
Contents 7
Contributors 9
Sperm Antigens 12
Proteomics of Human Spermatozoa 13
1.1.1 Introduction 13
1.1.2Technologies Used for the Study of the Sperm Proteome 14
1.1.2.1Two Dimensional Polyacrylamide Gel Electrophoresis 14
1.1.2.2 Difference in Gel Electrophoresis 16
1.1.2.3 Chromatographic Separation Methods 17
1.1.3 Conclusions 19
Methods of Analysis of Sperm Antigens Related to Fertility 23
1.2.1Introduction 23
1.2.2Two-Dimensional Gel Electrophoresis 24
1.2.2.1 Vectorial Labeling of Surface Proteins 25
1.2.2.2Identification of Fertility Related Sperm Antigens by Naturally Occurring Antisperm Antibodies 26
1.2.2.3 Differential Extraction 28
1.2.2.4Subcellular Fractionation of the Sperm 30
1.2.2.5Use of Polyclonal and Monoclonal Antibodies 31
1.2.2.6 Identification of GPI Anchored Proteins 31
1.2.2.7Two-Dimensional Differential in-Gel Electrophoresis (2D-DIGE) 32
1.2.2.8Identification of Phosphoproteins and Glycoproteins 32
1.2.2.9Identification and Mining of Low Abundant Proteins 32
1.2.2.10Coring of Protein Spots for Microsequencing and Cloning of Novel Genes 33
1.2.3cDNA Library Screening 34
1.2.4Summary 35
Sperm Surface Proteomics 42
1.3.1Introduction 42
1.3.1.1The Sperm Surface 42
1.3.1.2Function of Sperm Membrane Domains at Fertilization 43
1.3.1.3Sperm Surface Dynamics Before Fertilization 43
1.3.2Isolation of Sperm Surface Proteins 45
1.3.3Detection of Sperm Surface Proteins 47
1.3.3.1Tagging of Sperm Proteins and Peptides 47
1.3.3.2Surface Specific Considerations for Sperm Proteomics 48
1.3.4Comparison of Surface Proteomics of Human Sperm with Those of Mouse and Porcine or Bovine Sperms 49
1.3.4.1Human Sperm Proteomics 50
1.3.4.2Mouse Sperm Proteomics 51
1.3.4.3Porcine and Bovine Sperm Proteomics 51
1.3.5Conclusions 53
Sperm Functions Influenced by Immune Reactions 58
1.4.1Sperm Agglutination 58
1.4.2Sperm Apoptosis 60
1.4.3Sperm Motility 60
1.4.4Cervix Mucus Penetration 61
1.4.5Acrosome Reaction 62
1.4.6Zona Binding 64
1.4.7Oolemma Binding and Sperm–Egg Fusion 66
1.4.8Pronucleus Formation 68
1.4.9Conclusions 68
Antisperm Antibodies (ASA) 75
The Immune Privilege of the Testis 76
2.1.1Introduction 76
2.1.2 Blood Testis Barrier 77
2.1.3 Endocrine Regulation of Testicular Function and Immune Privilege 79
2.1.4 Mechanism of Maintenance and Disturbance of Testicular Immune Privilege 79
2.1.4.1 Macrophages 79
2.1.4.2 Dendritic Cells (DC) 80
2.1.5 Conclusions 81
Immune Chemistry of ASA 85
2.2.1Introduction 85
2.2.2Natural Autoantibodies 86
2.2.3ASA Antibodies Developed Prepuberty 87
2.2.4ASA Antibodies in Females 89
2.2.5ASA Antibodies in Males 90
2.2.6Carbohydrate-Mediated ASA Antibodies 92
2.2.7Conclusions 94
Sperm-Specific T Lymphocytes 97
2.3.1 General Characteristics of T Lymphocytes (from Janeway’s Immunobiology, 2007) 97
2.3.2 What is Known About Antigen-Specific T Cells in Immune Infertility? 98
2.3.3 T Cells in Semen 99
Site and Risk Factors of Antisperm Antibodies Production in the Male Population 103
2.4.2Risk Factors and Site of ASA Formation 104
2.4.2.1Chronic Obstruction of the MRT 104
2.4.2.2Infection and/or Inflammation of the MRT as Cause of ASA Formation 106
2.4.2.3Varicocele as Cause of ASA Formation 108
2.4.2.4Cryptorchidism as a Cause of ASA Formation 109
2.4.2.5Testicular Trauma, Surgery, and Torsion as Cause of ASA Formation 109
2.4.2.6Testicular Tumors as Cause of ASA Formation 110
2.4.2.7Homosexuality as Cause of ASA Formation 110
2.4.3Conclusions 111
Biologic Substrates Containing ASA 116
2.5.1ASA Are Immunoglobulins 116
2.5.2ASA in Serum 120
2.5.3ASA in Seminal Fluid 120
2.5.4ASA in Cervix Mucus 121
2.5.5ASA in Follicular Fluid 122
ASA in the Female 126
2.6.1 Introduction 126
2.6.2 Historical Background 126
2.6.3 More Recent Studies on ASA in Females 127
2.6.4 Clinical Evaluation of ASA 128
2.6.5 Postfertilization Effects of ASA on Fertility 128
2.6.6 Origins of ASA in Females 130
2.6.7 Conclusions 133
Sperm–Immobilizing Antibody and Its Target Antigen (CD52) 136
2.7.1Introduction 136
2.7.2Characterization of Sperm-Immobilizing Monoclonal Antibodies 136
2.7.3Hypothetical Structure of CD52 139
2.7.4Biological Function of CD52 141
2.7.5Animal Studies on CD52 142
The Clinical Impact ofSperm Antibodies 147
Male Autoimmune Infertility 148
3.1.1Introduction: Does Antisperm-Antibodies-Related Infertility Really Exist? 148
3.1.2Prevalence of Antisperm Antibodies 149
3.1.3Prognostic Studies 149
3.1.4Mechanisms of Fertility Impairment by Antisperm Antibodies: Clinical Relevance 150
3.1.4.1Effect on Semen Quality 150
3.1.4.2Interference with Cervical Mucus Penetration 151
3.1.4.3Complement-Mediated Cytotoxicity Through the Female Genital Tract 151
3.1.4.4Interference with Sperm/Egg Interaction 152
3.1.5Clinical Implications 152
Tests for Sperm Antibodies 157
3.2.1 Introduction 157
3.2.2 Detection of Sperm Antibody Classes 158
3.2.3 Testing Methods 158
3.2.3.1 Macro/Microagglutination and Immobilization 158
3.2.3.2 Enzyme-Linked Immunosorbent Assay and Immunofluorescence 159
3.2.3.3 Mixed Antiglobulin Reaction Test 159
3.2.3.4 Immunobead Test 161
3.2.3.5 Tests for Cervical Mucus 162
3.2.4 Comparison of ASA Tests 162
3.2.5 Interpretation and Significance of ASA Tests 163
3.2.6 Conclusions 164
Impact on Fertility Outcome 167
3.3.1Introduction 167
3.3.2Influences of ASA on Infertility Prognosis 168
3.3.3Steroid Treatment of ASA 169
3.3.4ASA Influences on Pregnancy Rate 171
3.3.5Conclusion 173
Sperm Antibodies and Assisted Reproduction 176
3.4.1Potential Mechanism of How Antisperm Antibodies (ASA) Impair Infertility 176
3.4.2Strategies for Treating Infertility Related to Antisperm Antibodies 176
3.4.3The Use of In Vitro Fertilization and Intracytoplasmic Sperm Injection for Antisperm Antibodies Counting Sperm 178
3.4.4The Use of In Vitro Fertilization and Intracytoplasmic Sperm Injection for Antisperm Antibodies in the Female Partner 179
3.4.5The Future 180
Treatment of Immune Infertility 186
3.5.1Discussion 186
3.5.2Treatment of Immune Infertility 186
3.5.2.1Immunosuppressive Therapies 187
3.5.2.2Assisted Reproductive Technologies (ART) 187
3.5.2.2.1IUI Procedure 187
3.5.2.2.2GIFT Procedure 188
3.5.2.2.3IVF Procedure 189
3.5.2.2.4 ICSI Procedure 189
3.5.2.3Laboratory Techniques 190
3.5.2.4Novel Recent Perspectives Using Defined Sperm Antigens 191
3.5.2.4.1Immunoelution of Antibodies with FA-1 Antigen 191
3.5.3Conclusion 192
Immune Contraception 196
Immunization with Sperm Antigens to Induce Contraception 197
4.1.1Introduction 197
4.1.2Discussion 198
4.1.2.1Rationale for Sperm Vaccine Development 198
4.1.2.2Sperm Antigens 199
4.1.2.3Passive Immunization and scFv Antibodies 201
4.1.3Conclusions 203
Immunocontraception in Wildlife Animals 208
4.2.1Immunocontraception in Wildlife Species 208
4.2.1.1Captive Population 208
4.2.1.2Wildlife Population 209
4.2.1.2.1Pest Species 209
4.2.1.2.2 Alien Species 209
4.2.1.3 Over-Abundant Wildlife 210
4.2.1.4 Transmitters of Zoonoses 210
4.2.2Development of Immunocontraceptive Vaccines for Wildlife Species 210
4.2.2.1 Porcine Zona Pellucida (PZP) 210
4.2.2.2 Gonadotropin-Releasing Hormone (GnRH) Vaccine 211
4.2.2.3 Other Antigens for Immuncontraception 211
4.2.3Delivery Methods 212
4.2.3.1Parenteral Immunisation 212
4.2.3.2 Oral Delivery via Baits 213
4.2.3.3 Plant Based Contraceptives 213
4.2.3.4 Virally-Vectored Immunocontraception (VVIC) 213
4.2.4Problems Connected with IC 214
4.2.4.1Animal Welfare and Health Issues 214
4.2.4.2 Behavioural Changes 215
4.2.4.3 Population Level Effects of Fertility Control 215
4.2.5Conclusion 216
Experience from Clinical Trials with Fertility Control Vaccines 221
4.3.1Introduction and Prologue 221
4.3.2Counter hCG Vaccine 222
4.3.2.1Diversity of hCG Vaccines 222
4.3.2.2 Necessity of Employing a Carrier 223
4.3.2.3 Phase II Efficacy Trials on HSD-hCG Vaccine 223
4.3.2.4 What Was the Shortcoming of the HSD Vaccine? 224
4.3.2.5 Revival of the hCG Vaccine 224
4.3.2.6 Additional Benefits of the hCG Vaccine 225
4.3.3LHRH Vaccine 225
4.3.3.1Recombinant LHRH Vaccine 226
Index 230

Produkt-Details

• Erscheint lt. Verlag: 17.8.2009
• Zusatzinfo: XI, 236 p.
• Verlagsort: Berlin
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Allgemeinmedizin
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Dermatologie
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Gynäkologie / Geburtshilfe
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Urologie
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie
• Themenwelt: Studium ► Querschnittsbereiche ► Infektiologie / Immunologie
• Schlagworte: Antigen • antisperm antibodies (ASA) • assisted reproduction • autoimmune infertility • clinical trial • Contraception • fertility • immune chemistry • immune contraception • immune contraceptives • Infertility • Lymphocytes • Medicine • Reproduction • sperm antibodies • sperm antigens • Spermatozoa • Testis • Treatment • Vaccine
• ISBN-10: 3-642-01379-1 / 3642013791
• ISBN-13: 978-3-642-01379-9 / 9783642013799