Every year there are new and exciting developments in assisted human reproduction, but how much do we really know about the underlying causes of infertility? This volume explores recent progress in the understanding of the genetics of spermatogenesis and male infertility. Topics include fundamental advances and current problems in the development and function of the testis, an outline of clinical findings in male infertility and an overview of the role of the Y chromosome in male fertility. Comprehensive critiques of posttranscriptional control during spermatogenesis, mammalian meiotic…mehr
Every year there are new and exciting developments in assisted human reproduction, but how much do we really know about the underlying causes of infertility? This volume explores recent progress in the understanding of the genetics of spermatogenesis and male infertility. Topics include fundamental advances and current problems in the development and function of the testis, an outline of clinical findings in male infertility and an overview of the role of the Y chromosome in male fertility. Comprehensive critiques of posttranscriptional control during spermatogenesis, mammalian meiotic sterility, and comparative genetics of human spermatogenesis from the perspective of yeast, Drosophila and mice provide a global overview of the field.
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.
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.
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