The Genetic Basis of Male Infertility

Clinical Aspects of Male Infertility.- 1 Introduction.- 2 The Elements of Standard Medical Workup.- 3 Aetiology of Male Infertility.- 4 Infertility Due to Genetic Disorders.- 5 Monogenic Diseases.- 6 Clinical Considerations of Genetic Abnormalities.- 7 Treatment of the Infertile Male.- References.- The Cell Biology and Molecular Genetics of Testis Determination.- 1 Introduction.- 2 Human Sex Determination is Chromosomally Based.- 3 Gonadal Sex Differentiation.- 4 The Testis-Determining Factor (TDF).- 5 The SOX9 Gene and Testis Determination.- 6 Orphan Nuclear Receptors and Sex Determination.- 7 Summary: A Genetic Cascade for Testis Determination.- References.- The Sertoli Cell-Germ Cell Interactions and the Seminiferous Tubule Interleukin-1 and Interleukin-6 System.- 1 Organisation of the Testis.- 2 Endocrine Regulation of Testicular Function.- 3 Paracrine Regulation of Testicular Function.- 4 Conclusion.- References.- Leydig Cell Function and Its Regulation.- 1 Introduction.- 2 Leydig Cell Morphology and Endocrine Function.- 3 Leydig Cell Development.- 4 Molecular Regulation of the Leydig Cell.- 5 Extrinsic Regulation of the Leydig Cell by Factors Other than LH.- 6 Leydig Cell Function and Infertility.- References.- Post-Transcriptional Control and Male Infertility.- 1 Introduction.- 2 The Need for Translational Control.- 3 Regulatory Elements in Untranslated Sequences.- 4 The Protamine mRNA Is Stored in a Ribonucleoprotein Particle.- 5 Sequence-Specific RNA Binding Proteins.- 6 Premature Translation of Prm1 mRNA.- 7 Activation of Translationally Repressed mRNAs.- 8 Orphan RNA Binding Proteins.- 9 Perspectives.- References.- An Integration of Old and New Perspectives of Mammalian Meiotic Sterility.- 1 Introduction.- 2 Sterility from a "Process-Oriented"Perspective.- 3 Sterility from the Perspective of Cell Cycle Checkpoint Control.- 4 Summary and Conclusions.- References.- Mutations of the Cystic Fibrosis Gene and Congenital Absence of the Vas Deferens.- 1 Introduction.- 2 CF and CBAVD: A Common Genetic Background.- 3 Pathogenesis of CBAVD.- 4 Spermatogenesis and Epididymal Length.- 5 Remaining Questions.- 6 Conclusions.- References.- Mitochondrial Function and Male Infertility.- 1 Introduction.- 2 Mitochondrial Diseases.- 3 Mitochondrial Function and Aging.- 4 Mitochondrial Biogenesis During Spermatogenesis.- 5 Mitochondrial Organization in the Spermatozoon.- 6 Regulation of Oxidative Phosphorylation in Mitochondria.- 7 Abnormal Mitochondria and Infertility.- 8 Mitochondrial Respiratory Chain, mtDNA and Infertility.- 9 Reactive Oxygen Species Generation and Human Spermatozoa.- 10 ATP Concentration, Creatine Kinase Activity and Infertility.- 11 Mitochondrial Inheritance.- 12 Conclusion.- References.- The Human Y Chromosome and Male Infertility.- 1 Structure of the Human Y Chromosome.- 2 Functions Associated with the Non-Recombining Region of the Human Y chromosome.- 3 Yq-Specific Genes and Gene Families.- 4 Function of Y-Specific Genes in Spermatogenesis.- 5 Which Genes Underlie the AZF Phenotypes?.- 6 Frequency of Yq Micro deletions.- 7 Microdeletions and Genotype/Phenotype Relationships.- 8 Mechanism of Y Chromosome Microdeletions.- 9 Y Chromosome Susceptibility Haplotypes.- 10 Perspectives.- References.- Spermatogenesis and the Mouse Y Chromosome: Specialisation Out of Decay.- 1 The Unique Y Chromosome.- 2 The Functions of the Mouse Y Chromosome.- 3 The Molecular Genetics of the Mouse Y Chromosome.- 4 Comparison of the Mouse and Human Y Chromosome Maps.- 5 Evolution of the Y Chromosome.- 6 General Conclusions.- 7The Future.- References.- The Comparative Genetics of Human Spermatogenesis: Clues from Flies and Other Model Organisms.- 1 Introduction.- 2 Model Organisms for Studying the Genetic Causes of Subfertility in Man.- 3 The Comparative Genetics of Male Germ Cell Differentiation in Flies and Man.- 4 Population Studies and Mutations Affecting Male Fertility in Flies and Man.- 5 Concluding Remarks.- References.