Note: Cover -- Half Title -- Title Page -- Copyright Page -- Dedication -- Contents -- Foreword -- Preface -- Editor -- Contributors -- 1. Primordial germ cells: Origin, migration and testicular development -- 1.1 Introduction -- 1.2 Origin of primordial germ cells -- 1.2.1 Molecular mechanisms during the origin of PGCs -- 1.3 Migration of PGCs -- 1.3.1 Molecular mechanisms during PGC migration -- 1.3.2 Migration stoppage of PGCs -- 1.4 Gonad and testicular development -- 1.4.1 Sertoli cell specification and expansion -- 1.4.2 Testis cord formation and compartmentalization -- 1.4.3 Formation of seminiferous tubules from testis cord by elongation -- 1.5 Conclusion and future directions -- Acknowledgments -- References -- 2. DNA methylation, imprinting and gene regulation in germ cells -- 2.1 Introduction -- 2.2 Dynamics of DNA methylation during PGC development -- 2.3 Mechanism and factors of DNA methylation erasure -- 2.4 Mechanism and factors of DNA methylation establishment -- 2.5 DNA methylation and histone modifications -- 2.6 Conclusion and future directions -- Acknowledgments -- References -- 3. Testicular stem cells, spermatogenesis and infertility -- 3.1 Introduction -- 3.2 Development of male germline cells -- 3.3 Testicular stem cells -- 3.3.1 As model for spermatogonial multiplication and stem cell renewal -- 3.3.2 Fragmentation model -- 3.3.3 Hierarchical model -- 3.4 Our views -- 3.4.1 Pluripotent very small embryonic-like stem cells (VSELs) are the most primitive stem cells in adult mammalian testis -- 3.4.2 Protocols to detect VSELs in testicular tissue -- 3.4.3 Pluripotent VSELs in adult testes undergo asymmetrical cell divisions -- 3.4.4 Pluripotent VSELs provide an alternate premise to explain testicular germ cell tumors -- 3.5 Discussion and future directions -- Acknowledgments -- References. , 4. Testicular germ cell apoptosis and spermatogenesis -- 4.1 Introduction -- 4.1.1 Proliferative phase of spermatogonia -- 4.1.2 Entry of spermatogenic cells into meiosis -- 4.1.3 Spermiogenesis and attainment of the motility appendage -- 4.1.4 Spermatogenic wave -- 4.2 Germ cell apoptosis -- 4.2.1 Pathways of apoptosis in testis -- 4.2.2 Fas/FasL system: Central regulator of testicular germ cell population -- 4.2.3 Activation of caspase-9 via the intrinsic pathway -- 4.2.4 P53 and spermatogenic cell apoptosis -- 4.3 Executioner caspases -- 4.4 Apoptosis of germ cells caused by hormonal, temperature and chemical insult -- 4.4.1 Hormonal variations -- 4.4.2 Heat stress -- 4.5 Testicular toxicants and germ cell apoptosis -- 4.6 Conclusion -- References -- 5. Hormonal regulation of spermatogenesis -- 5.1 Introduction -- 5.2 Spermatogenesis: An overview -- 5.3 Germ cell regeneration and death -- 5.4 Hypothalamic-pituitary-gonadal axis -- 5.5 Endocrine regulation of spermatogenesis -- 5.5.1 Follicle-stimulating hormone -- 5.5.2 Luteinizing hormone -- 5.5.3 Prolactin -- 5.5.4 Inhibin, activin and follistatin -- 5.5.5 Sex steroids -- 5.5.6 Metabolic hormones and growth factors -- 5.5.7 Other hormones -- 5.6 Sertoli cell interaction with Leydig and peritubular myoid cells -- 5.7 Role of hormones in spermiogenesis and spermiation -- 5.8 Conclusion -- References -- 6. GH-IGF1 axis in spermatogenesis and male fertility -- 6.1 Introduction -- 6.2 Growth hormone and male reproductive system -- 6.2.1 Effects on development -- 6.2.2 Effects on steroidogenesis -- 6.2.3 Effects on spermatogenesis -- 6.2.4 Other functions and mechanisms of regulation -- 6.3 Effects of altered growth hormone secretion on male fertility -- 6.4 Therapeutic use of growth hormone for male infertility -- 6.5 Conclusions -- References. , 7. Retinoic acid signaling in spermatogenesis and male (in)fertility -- 7.1 Introduction -- 7.2 Vitamin A and retinoids -- 7.2.1 Retinoid metabolism -- 7.2.2 Tissue targeting and retinoic acid signaling -- 7.3 Effects of RA on spermatogenesis -- 7.3.1 Evidence of retinoid acid effects in spermatogenesis -- 7.3.2 Expression of retinoids and retinoid receptors in the mammalian testis -- 7.3.3 RA signaling pathways in male germ cells and spermatogenesis -- 7.3.4 Influence of RA on sperm metabolism and oxidative stress -- 7.4 Abnormal RA signaling and human male infertility -- 7.5 Concluding remarks -- References -- 8. Testosterone signaling in spermatogenesis, male fertility and infertility -- 8.1 Introduction -- 8.2 Testosterone production and regulation of the steroidogenic pathway -- 8.3 Classical and nonclassical testosterone signaling -- 8.3.1 Classical testosterone signaling -- 8.3.2 Nonclassical testosterone signaling -- 8.4 Estrogen signaling and testosterone -- 8.5 Regulation of testosterone signaling by melatonin -- 8.6 Melatonin and human fertility -- 8.7 Aberrant testosterone signaling and male infertility -- 8.8 Testosterone therapy for azoospermic men -- 8.9 Conclusion and future directions -- References -- 9. Wnt signaling in spermatogenesis and male infertility -- 9.1 Introduction -- 9.2 Canonical Wnt signaling pathway -- 9.2.1 Wnt/Receptor interactions -- 9.2.2 Signal relay in the cytoplasm -- 9.2.3 Nuclear activity of ß-catenin -- 9.3 Wnt signaling in testis determination and development -- 9.4 Wnt signaling in male germ cell proliferation and maturation -- 9.5 Role of Wnt signaling in development and maintenance of Sertoli cells -- 9.6 Deregulated Wnt signaling and testicular tumor -- 9.7 Wnt signaling in male fertility -- 9.8 Conclusion and future directions -- References -- 10. MAPK signaling in spermatogenesis and male infertility. , 10.1 Introduction -- 10.2 Mitogen-activated protein kinases: An overview -- 10.3 Junction dynamics in spermatogenesis and its regulation -- 10.3.1 MAPK-ERK1/2 signaling in junction dynamics -- 10.3.2 MAPK-p38 in junction dynamics -- 10.3.3 JNK in junction dynamics -- 10.4 MAPK role in germ cell apoptosis -- 10.5 MAPKs in male infertility -- 10.6 Conclusion and future directions -- References -- 11. TGF-ß signaling in testicular development, spermatogenesis, and infertility -- 11.1 Introduction -- 11.2 Components of TGF-ß signaling cascade -- 11.2.1 Ligands -- 11.2.2 Receptors -- 11.2.3 SMAD proteins -- 11.3 Knockout mouse studies -- 11.4 TGF-ß superfamily action in testis -- 11.4.1 TGF-ß signaling -- 11.4.2 Activin signaling -- 11.4.3 Glial cell-derived neurotrophic factor signaling -- 11.4.4 Müllerian inhibiting substance signaling -- 11.4.5 Bone morphogenetic protein signaling -- 11.5 Reproductive disorders associated with aberrant TGF-ß signaling -- 11.5.1 Testicular cancer -- 11.5.2 Disrupted spermatogenesis -- 11.5.3 Leydig cell hyperplasia -- 11.5.4 Sertoli cell-only syndrome (germ cell aplasia) -- 11.5.5 Persistent Müllerian duct syndrome -- 11.6 TGF-ß cross talk with other pathways -- 11.7 Conclusion and future directions -- Acknowledgments -- References -- 12. Notch signaling in spermatogenesis and male (in)fertility -- 12.1 Introduction -- 12.2 Notch signaling: General concepts -- 12.3 How crucial is Notch signaling for spermatogenetic events? -- 12.4 Spermatogenesis in Caenorhabditis elegans and Notch signaling -- 12.5 Cross talk between Notch and other pathways in regulating spermatogenesis in C. elegans -- 12.6 Spermatogenesis in Drosophila melanogaster -- 12.7 Cross talk between Notch and other pathways in D. melanogaster -- 12.8 Spermatogenesis in Mus musculus -- 12.9 Cross talk between Notch and other pathways. , 12.10 Male infertility due to dysregulation of Notch signaling -- 12.11 Concluding remarks and future perspective -- Acknowledgments -- References -- 13. Hedgehog signaling in spermatogenesis and male fertility -- 13.1 Introduction -- 13.2 Hedgehog molecules -- 13.3 Hedgehog signaling in mammals -- 13.4 Hedgehog signaling in spermatogonial stem cell proliferation and differentiation -- 13.5 Indirect hedgehog signaling in SSCs -- 13.6 Direct hedgehog signaling in SSCs -- 13.7 Hedgehog signaling in spermatogenesis -- 13.7.1 Desert hedgehog -- 13.7.2 Sonic hedgehog (Shh) -- 13.7.3 Indian hedgehog -- 13.8 Conclusion -- References -- 14. mTOR signaling in spermatogenesis and male infertility -- 14.1 Introduction -- 14.2 mTOR-signaling pathway and mTOR complexes -- 14.3 Role of mTOR signaling in spermatogenesis -- 14.3.1 mTOR signaling in spermatogonial proliferation and Sertoli cell polarity -- 14.3.2 Role of mTOR signaling in blood-testes barrier -- 14.4 Clinical evidence of the role of mTOR in male fertility -- 14.5 Conclusion -- References -- 15. JAK-STAT pathway: Testicular development, spermatogenesis and fertility -- 15.1 Introduction -- 15.2 Model organisms for studying the JAK-STAT pathway -- 15.3 Components of the JAK-STAT pathway -- 15.3.1 Ligand molecules -- 15.3.2 Receptors -- 15.3.3 Janus kinases -- 15.3.4 Signal transducer for activation of transcription -- 15.3.5 Regulators of the JAK-STAT pathway -- 15.4 JAK-STAT signaling in gonad development -- 15.4.1 Germline sexual development in Drosophila melanogaster -- 15.5 JAK-STAT pathway and spermatogenesis -- 15.5.1 Drosophila testis stem cell niche -- 15.5.2 Intercellular communications -- 15.5.3 Role of JAK-STAT in maintenance of stem cell niche -- 15.5.4 Integration of signaling pathways for stem cell maintenance -- 15.6 JAK-STAT pathway in human sperm capacitation. , 15.7 JAK-STAT pathway in sperm motility.

Note: Intro -- Preface -- About the Editors -- Contents -- Contributors -- Abbreviations -- Part I: Understanding Spermatogenesis and Male Fertility -- 1: Overview of the Male Reproductive System -- 1.1 Origin of the Reproductive Organs -- 1.2 Anatomy and Physiology of the Male Reproductive System -- 1.2.1 Scrotum -- 1.2.2 Testes -- 1.2.2.1 Leydig Cells -- 1.2.2.2 Sertoli Cells -- 1.2.2.3 Blood-Testis Barrier -- 1.2.2.4 Germ Cells -- 1.2.2.5 Spermatogenesis -- 1.3 Testosterone -- 1.4 Sperm Transport -- 1.4.1 Epididymis -- 1.4.2 Duct System -- 1.5 Seminal Vesicle -- 1.6 Prostate Gland -- 1.7 Bulbourethral Gland -- 1.8 Urethra -- 1.9 Penis -- 1.10 Structure of Human Mature Sperm -- References -- 2: Embryonic Development of the Testis -- 2.1 Introduction -- 2.2 Overview of the Development of the Testes -- 2.3 Formation of the Primitive Gonads -- 2.4 Cell Lineages -- 2.4.1 Primordial Germ Cells -- 2.4.2 Somatic Cell Lineages in the Male Testis -- 2.4.2.1 Sertoli Cells -- 2.4.2.2 Leydig Cells -- 2.4.2.3 Peritubular Cells -- 2.5 Testicular Descent -- 2.6 Perinatal Events in Testicular Maturation -- 2.7 Cryptorchidism: The Failure of Testicular Descent -- 2.8 Testicular Descent: Associated Disorders -- References -- 3: HPG Axis: The Central Regulator of Spermatogenesis and Male Fertility -- 3.1 Introduction -- 3.2 The Hypothalamic-Pituitary-Gonadal Axis -- 3.3 GnRH Neurons: Origin and Development -- 3.4 Role of FSH and LH in Spermatogenesis -- 3.5 FSH and LH in Human Male Infertility -- 3.6 Endocrine Disruptors: Modulators of the HPG Axis -- 3.7 Melatonin and HPG Axis in Reproductive Health -- References -- 4: Sperm Maturation in Epididymis -- 4.1 Introduction -- 4.2 Epididymal Morphology -- 4.3 Epididymis: The Site of Sperm Maturation -- 4.4 Epididymal Transcriptome and Proteome -- 4.5 Epididymal Secretome. , 4.6 Maturational Changes in Sperm During Epididymal Transit -- 4.7 Development of Motility Potential in Sperm During Epididymal Transit -- References -- 5: Sperm Capacitation: The Obligate Requirement for Male Fertility -- 5.1 Introduction -- 5.2 What Is Sperm Capacitation? -- 5.3 Hallmarks of Capacitation -- 5.3.1 Hyperactivation -- 5.3.2 Acrosome Reaction -- 5.3.3 Protein Tyrosine Phosphorylation -- 5.4 Diagnosis and Prognosis of Male Infertility/Fertility: Importance of Capacitation-Based Sperm Function Tests -- 5.4.1 Monitoring Hyperactivation (HA) -- 5.4.2 Monitoring Acrosome Reaction (AR) -- 5.4.3 Monitoring Tyrosine Phosphorylation (pY) -- 5.5 From Bench to Clinics: Male Fertility Biomarkers and ARTs -- References -- 6: Genomic Landscape of Human Y Chromosome and Male Infertility -- 6.1 Introduction -- 6.2 Y Chromosome and the Azoospermia Factor Region (AZF) -- 6.2.1 AZFa -- 6.2.2 AZFb -- 6.2.3 AZFc -- 6.3 Sex-Determining Region Y (SRY) -- 6.4 Y Chromosome Has Significance Beyond Sex Determination and Spermatogenesis -- 6.5 Oncogenic Role of Y Chromosome -- 6.6 Gene Conversions -- 6.7 Y Chromosome: Evolution and Degeneration -- 6.8 Y Chromosome: Regulation of Autosomal Gene Expression -- 6.9 Future Prospects -- References -- 7: Seminal Decline in Semen Quality in Humans Over the Last 80 years -- 7.1 Introduction -- 7.2 Hallmark Studies Describing a Decline Over the Past 80 years -- 7.3 Factors Alleged for Deteriorating Semen Quality -- 7.4 Discussion and Future Directions -- References -- Part II: Causes of Male Infertility -- 8: Syndromic Forms of Male Infertility -- 8.1 Introduction -- 8.2 Syndromes with Chromosomal Aneuploidy -- 8.2.1 Klinefelter's Syndrome (47,XXY) -- 8.2.2 Jacob's Syndrome (47,XYY) -- 8.3 Syndromes with Gene Mutations -- 8.3.1 Kallmann Syndrome. , 8.3.2 Androgen Insensitivity Syndrome (AIS) -- 8.3.3 Noonan Syndrome -- 8.3.4 Cystic Fibrosis -- 8.4 Rare Syndromes of Male Infertility -- 8.4.1 Myotonic Dystrophy 1 -- 8.4.2 Primary Ciliary Dyskinesia -- 8.4.3 Kearns-Sayre Syndrome -- 8.4.4 Aarskog-Scott Syndrome -- 8.4.5 Persistent Müllerian Duct Syndrome -- 8.4.6 Prader-Willi Syndrome -- 8.4.7 Deafness Infertility Syndrome -- References -- 9: Cystic Fibrosis, CFTR Gene, and Male Infertility -- 9.1 Introduction -- 9.2 Pathogenesis -- 9.3 Epidemiology -- 9.4 Diagnosis -- 9.5 Fertility in Men Having CF -- 9.6 CFTR-Related Disorders Associated with Male Infertility -- 9.6.1 Congenital Bilateral Absence of the Vas Deferens (CBAVD) -- 9.6.2 CBAVD Having Renal Anomalies (CBAVD-URA) -- 9.6.3 Congenital Unilateral Absence of the Vas Deferens (CUAVD) -- 9.6.4 Ejaculatory Duct Obstruction -- 9.7 Infertility Management in CBAVD -- 9.7.1 Assisted Reproduction -- 9.7.2 Genetic Counseling -- 9.7.3 Sperm Collection Techniques -- 9.7.3.1 Percutaneous Epididymal Sperm Aspiration (PESA) -- 9.7.3.2 Microsurgical Epididymal Sperm Aspiration (MESA) -- 9.8 Our Experience -- 9.8.1 CFTR Gene Variants in Isolated CBAVD in Indian Population -- 9.8.2 CBAVD-URA -- 9.9 Future Perspectives -- References -- 10: Oxidative Stress and Male Infertility -- 10.1 Introduction -- 10.2 Significance of ROS in Sperm Function -- 10.3 Sources of ROS in Semen -- 10.4 Oxidative Stress: Potential Origins -- 10.5 Oxidative Stress: A Major Contributor to the Disease Pathology -- 10.6 Oxidative Stress and Declining Semen Quality -- 10.7 Oxidative Stress Correlates with Erectile Dysfunction -- 10.8 Oxidative Stress: Clinical Perspectives and Laboratory Assessment -- 10.9 Management of Oxidative Stress-Induced Male Infertility -- 10.9.1 Antioxidants -- 10.9.2 Other Therapies -- References. , 11: Obesity, Spermatogenesis, and Male Infertility -- 11.1 Introduction -- 11.2 Obesity and Reproduction -- 11.3 Obesity Compromises Testosterone Production -- 11.4 Obesity Disturbs Testosterone: Estrogen Ratio -- 11.5 Obesity Disturbs Scrotal Thermal Regulation -- 11.6 Obesity Increases DNA Damage -- 11.7 Obesity Leads to Transgenerational Epigenetic Effects -- 11.8 microRNAs (miRNAs), Obesity, and Male Infertility -- 11.9 Obesity Correlates with Erectile Dysfunction -- 11.10 Obesity, Adipokines, and Male Infertility -- 11.11 Impact of Childhood Obesity on Puberty -- 11.12 Effect of Maternal Obesity on Fetal Health -- 11.13 Obesity and Quality of Sexual Life -- 11.14 Animal Studies on Obesity and Fertility -- 11.15 Management of Obesity-Related Infertility -- References -- 12: Sexually Transmitted Infections and Male Infertility: Old Enigma, New Insights -- 12.1 Introduction -- 12.2 STD Pathogens: Locus of Infection and Resultant Pathology in the Male Urogenital Tract -- 12.2.1 Urethritis -- 12.2.2 Epididymitis and Orchitis -- 12.2.3 Prostatitis -- 12.2.4 Vesiculitis -- 12.3 Bacterial Infections and Male Infertility -- 12.3.1 Neisseria gonorrhoeae -- 12.3.2 Chlamydia trachomatis -- 12.3.3 Treponema pallidum -- 12.3.4 Mycoplasma Species -- 12.3.5 Ureaplasma Species -- 12.4 Viral Infections and Associated Male Infertility -- 12.4.1 Human Papillomavirus -- 12.4.2 Human Cytomegalovirus -- 12.4.3 Human Immunodeficiency Virus -- 12.4.4 Herpes Simplex Virus -- 12.4.5 Hepatitis B Virus (HBV) -- 12.4.6 Hepatitis C Virus or HCV -- 12.5 Protozoan Infections and Male Infertility -- 12.5.1 Trichomonas vaginalis -- References -- 13: Cytogenetic Factors in Male Infertility -- 13.1 Introduction -- 13.2 SRY Gene Translocation on X Chromosome or Autosomes -- 13.3 Somatic Chromosome Aneuploidies -- 13.3.1 47,XXY. , 13.3.2 47,XYY -- 13.4 Meiotic Abnormalities and Sperm Aneuploidies -- 13.5 Chromosomal Translocations and Inversions -- 13.6 The Interchromosomal Effects -- 13.7 Sperm Aneuploidies and Adverse Reproductive Outcomes -- 13.8 Advances in Human Molecular Cytogenetics: From Chromosomes to SNPs -- 13.8.1 Multiplex-Fluorescence In Situ Hybridization (M-FISH) and Spectral Karyotyping (SKY) -- 13.8.2 Combining Binary and Ratio Labelling (COBRA-FISH) -- 13.8.3 Array-Based CGH -- 13.8.4 Single-Nucleotide Polymorphism Array (SNP Array) -- 13.8.5 Next-Generation Sequencing (NGS) -- References -- 14: Autosomal Genes in Male Infertility -- 14.1 Introduction -- 14.2 Genes in Gonadal Development and Fertility: Establishing Fertility -- 14.3 Autosomal Pathways in Spermatogenesis -- 14.3.1 Infertility and Apoptosis: Eliminating the Unfit -- 14.3.1.1 Intrinsic Pathway -- 14.3.1.2 Extrinsic Pathway -- 14.3.2 DNA Damage, Replication and Repair Pathways: Keeping It Correct -- 14.3.3 Hormonal/Endocrine Pathways -- 14.4 Standalone Drivers from the Autosomal Store -- References -- 15: Sex Chromosomal Genes in Male Infertility -- 15.1 Introduction -- 15.2 Y Deletions Are Common in Infertility -- 15.3 Screening of Y deletions -- 15.4 Classical Deletions/Microdeletions -- 15.5 Partial Deletions -- 15.5.1 gr/gr Is a Risk Factor for Male Infertility -- 15.5.2 b2/b3 May Increase Risk in Some Ethnic Groups -- 15.6 Y Haplotypes -- 15.6.1 Terminology and Nomenclature of Y Haplotypes -- 15.6.2 Y Haplotypes and Male Infertility -- 15.7 Genes on the X Chromosome -- 15.8 X-Linked Testis-Specific or Testis-Enriched Genes -- 15.9 Mutation Analysis of Human X-Linked and Testis-­Enriched Genes -- 15.9.1 A-Kinase Anchor Protein 4 (AKAP4) -- 15.9.2 Fetal and Adult Expressed 1 (FATE1) -- 15.9.3 TATA Box Binding Protein-Associated Factor 7 Like (TAF7L). , 15.9.4 Ubiquitin-Specific Peptidase 26 (USP26).