MOLECULAR MECHANISMS IN SPERMATOGENESIS

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Preface Contents About the Editors The Seminiferous Epithelial Cycle of Spermatogenesis: Role of Non-receptor Tyrosine Kinases Introduction Junctional and Cytoskeletal Dynamics in the Testis NRTKs: Membrane Targeting and Dynamic Localization NRTKs and Endocytosis During Spermatogenesis Concluding Remarks References The Good, the Bad and the Ugly of Testicular Immune Regulation: A Delicate Balance Between Immune Function and Immune Privilege Introduction The Good: Testis Immune Privilege Mechanism(s) of Immune Privilege The Bad and the Ugly: The Testis as a Sanctuary Site for Pathogens and Cancer Viruses Bacteria Cancer Activation of Innate and Adaptive Immunity Summary References Immunologic Environment of the Testis Introduction Immune Privilege in the Testis Features of Immune Privilege in the Testis Testicular Immunosuppressive Milieu Negative Immunoregulatory System Role of Leukocytes in Immune Privilege Peripheral Immune Tolerance to Male Germ Cell Antigens Innate Defense Against Microbial Infections in the Testis Interferons and Antiviral Protein Antimicrobial Defensins Pattern Recognition Receptors (PRRs) TLRs in Sertoli Cells PRRs in Leydig Cells PRRs in Male Germ Cells TLR-Initiated Immune Responses in Testicular Macrophages (TMs) Orchitis Infectious Orchitis Autoimmune Orchitis Conclusions References Unraveling the Regulation of Cancer/Testis Antigens in Tumorigenesis Through an Analysis of Normal Germ Cell Development in Rodents Introduction Approaches Used for Analysis A Subset of CT Antigens Belongs to the Core Fitness Gene Family Multiple CT Antigens Are Under the Control of Super-Enhancers (SEs) DNA Methyltransferase DNMT1 Is Involved in the Regulation of CT Antigen Expression The Expression of CT Antigen TAF7L Is Regulated by DNA Methylation in Cancers TAF7L Regulates the Expression of Other CT Antigens Discussion and Concluding Remarks Summary References Coxsackievirus and Adenovirus Receptor (CXADR): Recent Findings and Its Role and Regulation in Spermatogenesis Introduction CXADR Isoforms and Their Molecular Structure Phenotypes of CXADR Knockout Mice Functions and Regulation of CXADR CXADR as a Virus Receptor CXADR as a Cell Junction Component CXADR as a Signalling Platform Role of CXADR in Spermatogenesis Regulation of CXADR in Testicular Cells Conditional CXADR Knockouts Unfold the Physiological Significance of CXADR Omics Analyses of SC-CXADR−/− Testes Future Perspectives and Concluding Remarks References Leydig Cell and Spermatogenesis Introduction The Development of Leydig Cells The Fetal Leydig Cell The Neonatal Leydig Cell The Adult Leydig Cell Steroidogenesis in Leydig Cells The Sources of Cholesterol in Leydig Cells Cholesterol Transportation Within Leydig Cells Androgen Synthetic Pathways CYP11A1 Catalysis HSD3B Catalysis CYP17A1 Catalysis HSD17B3 Catalysis SRD5A1 Catalysis AKR1C14 Catalysis Testosterone Secretion Regulation of Leydig Cell Development and Function Onset and Maintenance of Spermatogenesis by Testosterone Pharmacological Treatment of Androgens Androgen Action on Sertoli Cells Conclusion References Motor Proteins and Spermatogenesis Introduction Sertoli Cell Cytoskeletons in the Testis Actin-Based Cytoskeleton MT-Based Cytoskeleton Motor Proteins MT-Based Motor Proteins: Dynein and Kinesin Dynein Kinesin F-actin-Based Motor Proteins: Myosins Myosins Concluding Remarks and Future Perspectives References Male Infertility in Humans: An Update on Non-obstructive Azoospermia (NOA) and Obstructive Azoospermia (OA) Introduction Genetic Mutation(s) DNA Methylation Chromosomal Aberrations and Y chromosome (Yq) Microdeletions Concluding Remarks and Future Perspectives References Androgen Actions in the Testis and the Regulation of Spermatogenesis Testosterone Production and Levels in the Testis A Concise Review of Spermatogenesis and the Processes that Require Testosterone Testosterone Signaling Pathways The Absence of Testosterone Signaling Blocks Testis Descent Causing Azoospermia Cell- and Temporal-Specific Expression of AR in the Testis Androgen-Mediated Autocrine and Paracrine Signaling Between Somatic Cells in the Testis Testosterone Is Required to Maintain the Blood-Testis Barrier Over-Expression of AR in Sertoli Cells Results in Fewer Sertoli and Germ Cells Does Testosterone Regulate the Number of Gonocytes and Spermatogonia? Evidence against Expression of Functional AR in Germ Cells after Birth Expansion of Spermatogonia Is Associated with Testosterone Signaling Androgen and AR Are Required to Complete Meiosis Androgen Is Required for the Attachment and Release of Elongated Spermatids Identification of Androgen-Regulated Genes Using Mouse Models Synergism and Antagonism of Androgen and FSH Signaling Summary and Future Directions References Use of Molecular Modeling to Study Spermatogenesis: An Overview Using Proteins in Sertoli Cells Spermatogenesis Sertoli Cell Proteins: An Overview Homology Modelling, Molecular Docking Analysis of Proteins in Understanding Sertoli Cell Function and Spermatogenesis References Destruction or Reconstruction: A Subtle Liaison between the Proteolytic and Signaling Role of Protein Ubiquitination in Spermatogenesis Background Proteolytic Functions of the Ub System along Spermatogenesis Spermatogonial Development Meiosis Meiotic Entry Meiotic Progression Spermiogenesis Chromatin Condensation Acrosome Biogenesis and Axoneme Development Mitochondria Reorganization Non-proteolytic Functions of the Ub System along Spermatogenesis NP-Ub System and Meiotic DNA NP-Ub System and Spermiogenesis NP-Ub System and Activation of Silenced Genes NP-Ub System and Acrosome Biogenesis Passing of the Baton Between Non-Proteolytic Functions and Proteolytic Functions of the Ub System in Sperm Biology Concluding Remark References Spermiation: Insights from Studies on the Adjudin Model Introduction Adjudin Targets both Actin- and Microtubule (MT)-Based Cytoskeletons Rats Treated with Adjudin as a Model for Studying Sperm Release Rats Treated with Adjudin as a Model for Studying Elimination of the Spermatid Cytoplasm Rats Treated with Adjudin as a Model for Studying Spermatid Orientation Concluding Remarks References Regulation of Human Spermatogenesis Introduction Leydig Cells Sertoli Cells Peritubular Cells Immune Cells and Inflammatory Regulation Germ Cells Spermatogonia Spermatocytes Spermatids Genes and Non-Coding RNA Conclusion References Testicular Torsion and Spermatogenesis Introduction Patient Presentation Patient Evaluation Mechanisms of Testicular Torsion Clinical Management Effect on Fertility and Spermatogenesis Abnormal Semen Parameters Clinical Pregnancy Rates Mechanisms of Torsion-Induced Deficits to Spermatogenesis Ischemia, Ischemia-Reperfusion (I/R) Injury and Oxidative Stress Treating Ischemia-Reperfusion Injury & Oxidative Stress Pharmacologic Agents Natural Extracts Endogenous Hormones & Analogues Physical Therapies Other Mechanisms Auto-Antibodies Congenital Abnormalities & Intermittent Torsion Conclusion References Testis Toxicants: Lesson from Traditional Chinese Medicine (TCM) Introduction α-Solanine Inhibits Cell Proliferation in Mouse Testes Concluding Remarks and Future Perspectives References