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.