Cover -- Half-title -- Title -- Copyright -- Contents -- Preface -- List of contributors -- 1 Mammalian spermatogenesis and sperm structure: anatomical and compartmental analysis -- 1.1 Introduction -- 1.2 Structure and function of mammalian spermatozoon -- 1.2.1 Sperm head -- 1.2.2 Sperm flagellum -- 1.3 Spermatogenesis -- 1.3.1 Germ cell migration and establishment of seminiferous epithelium -- 1.3.2 Architecture of the seminiferous epithelium and blood-testis barrier -- 1.3.3 Spermatogenic cycle of seminiferous epithelium -- 1.3.4 Spermatogenic wave of seminiferous epithelium -- 1.3.5 Proliferative and meiotic phase of spermatogenesis -- 1.3.6 Haploid phase of spermatogenesis: spermiogenesis and spermiation -- 1.3.7 Regulation of spermatogenesis -- 1.3.8 Role of the testis in the sustenance of epididymal function -- 1.4 Changes to sperm structure during fertilization -- 1.4.1 Complementation of organelle reduction in male and female gametes -- 1.4.2 Changes to sperm head structure during fertilization -- 1.4.3 Sperm incorporation in the ooplasm, oocyte activation and zygotic development -- 1.5 Conclusions -- Acknowledgments -- REFERENCES -- 2 Sperm chromatin stability and susceptibility to damage in relation to its structure -- 2.1 Introduction: the malleable sperm genome -- 2.2 Sperm chromatin structure and fertility -- 2.3 Sperm DNA damage assays and human fertility -- 2.4 Sperm apoptosis -- 2.5 Sperm nucleases -- 2.6 Conclusions -- REFERENCES -- 3 Genomic and proteomic approaches to defining sperm production and function -- 3.1 Introduction -- 3.2 How useful is a semen assessment for the diagnosis and prognosis of male infertility? -- 3.3 The sperm and testis transcriptome -- 3.3.1 Sperm mRNA -- 3.3.2 The transcriptome of the testis -- 3.3.3 The sperm proteome -- 3.4 Mouse models for male infertility: the role of knockout mice.

3.4.1 Akap4 -- 3.4.2 Vdac3 -- 3.5 Sperm transit in the female tract -- 3.5.1 Angiotensin-converting enzyme -- 3.5.2 Fertilin and calmegin -- 3.6 Capacitation and hyperactivation -- 3.6.1 Platelet activating factor -- 3.6.2 Acid sphingomyelinase -- 3.6.3 CatSper1/CatSper2 -- 3.6.4 PMCA4 -- 3.7 Sperm-zona pellucida interaction -- 3.7.1 Phospholipase… -- 3.8 Translating mouse models to the human: how do we go from knockout to diagnosis of male fertility -- 3.9 What's the future for the diagnosis of sperm dysfunction and male infertility? -- Acknowledgements -- REFERENCES -- 4 Sperm maturation in the human epididymis -- 4.1 Introduction -- 4.2 Sperm maturation in the human epididymis -- 4.2.1 Sperm transit -- 4.2.2 Morphology -- 4.2.2.1 Sperm heads -- 4.2.2.2 Cytoplasmic droplets -- 4.2.2.3 Sperm tails -- 4.2.3 Motility -- 4.2.4 Sperm-zona binding -- 4.2.5 Acrosome reaction -- 4.2.6 Acrosin content -- 4.2.7 Sperm oocyte binding and fusion -- 4.2.8 Chromatin condensation -- 4.2.9 Fertilising ability in vivo and in vitro -- 4.3 Sperm storage in the human epididymis -- 4.3.1 Sperm numbers -- 4.3.2 Sperm protection -- 4.4 Sperm volume regulation -- 4.4.1 Ejaculated spermatozoa -- 4.4.2 Epididymal spermatozoa -- 4.5 Epididymal fluid -- 4.6 Epididymal proteins involved in sperm maturation -- 4.6.1 Solely testicular proteins -- 4.6.2 Testicular and epididymal proteins -- 4.6.3 Solely epididymal proteins -- 4.6.4 Interaction of proteins with spermatozoa -- 4.7 Summary -- Acknowledgments -- REFERENCES -- 5 Controls of sperm motility -- 5.1 Introduction -- 5.2 Experimental approaches to study sperm movement -- 5.3 The flagellum -- 5.3.1 The axoneme -- 5.3.2 Outer dense fibers, fibrous sheath and mitochondrial sheath -- 5.3.3 Morphological abnormalities -- 5.4 Motility in marine species with external fertilization -- 5.4.1 Ionic factors.

5.4.2 Protein phosphorylation -- 5.4.3 Chemotaxis -- 5.5 Motility in mammalian species with external fertilization -- 5.5.1 Sources of ATP -- 5.5.2 Bicarbonate, cAMP and PKA -- 5.5.3 Other phosphorylation events associated with sperm motility -- 5.5.4 Other sperm enzymes or factors involved in motility -- 5.5.5 Seminal plasma factors that affect sperm motility -- 5.5.6 Sperm hyperactivation -- 5.5.7 Sperm chemotaxis -- 5.6 Conclusion -- Acknowledgment -- REFERENCES -- 5 6egulation of capacitation -- 6.1 Introduction -- 6.2 Heterogeneity in sperm populations and in sperm -- 6.3 Molecular basis of capacitation -- 6.3.1 HCO-3 and the cyclic adenosine monophosphate pathway in mammalian sperm -- 6.3.2 Changes that occur at the level of the plasma membrane (see Fig. 6.2) -- 6.3.2.1 Early events (see Fig. 6.3) -- 6.3.2.2 Late events (see Fig. 6.3) -- 6.3.3 Sperm plasma membrane potential -- 6.3.4 Phosphorylation events during capacitation -- 6.3.5 Ca and capacitation -- 6.4 Hyperactivated motility -- 6.5 Preparation for the acrosome reaction -- 6.6 Some precautions when working on sperm capacitation -- 6.7 Discussion and summary -- Acknowledgments -- REFERENCES -- 7 Reactive oxygen species: friend or foe -- 7.1 Introduction -- 7.2 What are ROS? -- 7.3 Detection of ROS in the male germ line -- 7.4 Impact of oxidative stress on spermatozoa -- 7.5 Origins of oxidative stress associated with defective sperm function -- 7.6 The physiological role of ROS -- 7.7 Conclusions -- REFERENCES -- 8 Testing sperm manufacturing quality: the sperm-zona binding assay -- 8.1 Introduction -- 8.2 Assessment of the subfertile patient: the andrological examination and the basic semen analysis -- 8.3 The extended semen evaluation -- 8.3.1 Sperm function tests -- 8.3.2 Sperm-ZP binding assays -- 8.3.3 Acrosome reaction assays.

8.4 Clinical use of sperm function tests: directing treatment to a defined therapy and predictive value for IVF and pregnancy outcome -- 8.5 Conclusions -- REFERENCES -- 9 Genetics: a basic science perspective -- 9.1 Introduction -- 9.1.1 Chromosome abnormalities in infertile men -- 9.1.2 Genomic AZF gene deletions in infertile men -- 9.1.3 Single gene defects in infertile men -- 9.1.3.1 The CFTR-gene in 7q31.2 -- 9.1.3.2 The Kallmann 1 (KAL-1) gene locus -- 9.1.3.3 The AR gene locus -- 9.1.3.4 Follicle-steroid hormone/luteinizing hormone receptor (FSHR/LHR) locus -- 9.1.3.5 INSL3 and LGR8-GREAT gene loci are functional for testis descent -- 9.1.3.6 DNA polymerase G (POLG) locus -- 9.1.3.7 Gene defects causing Kartagener syndrome and Globozoospermia -- 9.2 Male fertility marker genes -- 9.2.1.1 PHGPx expression in the male germ line -- 9.2.1.2 PRM-1/PRM-2 expression and sperm chromatin condensation -- Acknowledgements -- REFERENCES -- 10 Sex chromosome abnormalities and male infertility: a clinical perspective -- 10.1 Introduction -- 10.2 Y chromosome -- 10.2.1 Azoospermia factor -- 10.2.2 Mutations in Y chromosome genes that cause infertility -- 10.2.3 Limitations of Y chromosome testing -- 10.2.4 Prognosis for AZF deletions: ejaculated sperm -- 10.2.5 Prognosis for AZF deletions: testis histological findings -- 10.2.6 Prognosis for AZF deletions: testis sperm retrieval and intra-cytoplasmic sperm injection results -- 10.2.7 Prognosis for AZF deletions: offspring -- 10.3 X chromosome -- 10.3.1 Structural abnormalities of the X chromosome associated with male infertility -- 10.3.2 Studies on the mouse X chromosome -- 10.3.3 Clinical studies of human X-linked genes and infertility -- 10.3.4 Why does the X chromosome have a role in male fertility? -- 10.4 Syndromes involving the sex chromosomes -- 10.4.1 Klinefelter syndrome (incidence 1:500).

10.4.2 XYY syndrome (1:1000) -- 10.4.3 Kallman syndrome (1:30,000) -- 10.4.4 XX male syndrome (1:20,000) -- 10.4.5 Mixed gonadal dysgenesis (rare) -- 10.4.6 SRY Gene Defects (rare) -- 10.4.7 Androgen receptor gene mutations (1:60,000) -- 10.4.8 Kennedy disease (rare) -- 10.4.9 Persistent Mullerian duct syndrome (rare) -- 10.5 Conclusions -- REFERENCES -- 11 Epigenetic patterning in male germ cells: importance of DNA methylation to progeny outcome -- 11.1 Epigenetics and gene expression -- 11.2 Genomic methylation reprogramming in the germ line: dynamics and timing -- 11.2.1 Mouse studies -- 11.2.1.1 Erasure of methylation patterns in the germ line -- 11.2.1.2 Differential timing of methylation pattern acquisition between germ lines -- 11.2.1.2 Differential timing of methylation pattern acquisition between germ lines -- 11.2.1.3 DNA methylation and testis-specific gene expression -- 11.2.1.4 Maintenance of DNA methylation patterns in early embryos -- 11.2.2 Human studies -- 11.2.2.1 Erasure, establishment and maintenance of genomic methylation -- 11.3 The mammalian DNMTs -- 11.4 DNMT1 -- 11.4.1 Mouse studies -- 11.4.2 Expression of DNMT1 in the reproductive system of humans and other species -- 11.5 DNMT3a and DNMT3b -- 11.5.1 Mouse studies -- 11.5.2 DNMT3A and DNMT3B in the reproductive system of humans and other species -- 11.6 DNMT3L -- 11.6.1 Mouse studies -- 11.6.2 DNMT3L in the reproductive system of humans -- 11.7 Germ line epigenetic inheritance: regulation and dysregulation -- 11.7.1 Mechanisms of epigenetic inheritance in genomic imprinting -- 11.7.1.1 The H19 subdomain: a model for paternally inherited imprinting marks -- 11.7.2 Sex chromosome inactivation during spermatogenesis -- 11.7.3 Errors in erasure, acquisition or maintenance of DNA methylation patterns -- 11.7.3.1 Single-site loss of DNA methylation.

11.7.3.1.1 Imprinting disorders.