DAX1, testes development role 7, 8 DFFRY, spermatogenesis role 49 DMRT genes, male sex differentiation role 15

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1 Subject Index N-Acetylcysteine, sperm quality effects 71 Ambiguous genitalia, origins 1, 2 Anti-Müllerian hormone function 13 receptors 13 Sertoli cell secretion 10, 38 Apoptosis assays in testes 73, 74 caspase activation pathways caspase-independent pathways 61 definition 56 germ cells development 61 mitochondrial membrane potential dissipation and electron transport disruption 70, 71 mitochondrial permeability transition and release of apoptogenic factors 69 pathology 62 prevention with anti-inflammatory drugs 69 prospects for study 74 reactive oxygen species generation 71, 72 regulation Bcl-2 59, 60, 64, 72 cell-cell interactions 62, 63 estrogen 64, 65 Fas FLIPs 60 follicle-stimulating hormone 63, 64 heat shock proteins 60 IAPs 60 intracellular regulators 72, 73 luteinizing hormone 63 nuclear factor- B 68 p53 60, 72, 73 spermatogonia 45, 61, 62 testosterone 63 tumor necrosis factor- receptor phases 56, 57 AZF (azoospermia factor), spermatogenesis role 49 Bcl-2, apoptosis regulation in germ cells 59, 60, 64, 72 Blood supply blood-testis barrier 28, 29 testicular anatomy and function 25 Bone marrow transplantation, testicular damage 127 P-Cadherin, structural organization of testes 11, 12 Carcinoma in situ, features 111, 112 Caspases, activation pathways Cathepsins, structural organization of testes 12, 13 Chemotherapy fertility preservation, see Infertility germ cell loss 125 Leydig cell failure 127 protective agents

2 Collagen, structural organization of testes 12 CREMT (cyclic AMP-responsive element modulator T) spermatogenesis role 50 Cryopreservation female gonadal tissue 150 semen 130, 139 testicular tissue 130, 149 Cryptorchidism associated disorders 106, 107 diagnosis 104, 105 etiology 105, 106 gene mutations 105, 106 incidence 106 regulation of testicular descent 105 treatment 107, 108 Cytoskeleton, structural organization of testes 12 DAX1, testes development role 7, 8 DFFRY, spermatogenesis role 49 DMRT genes, male sex differentiation role 15 E2, spermatogenesis role 50 Emx2, indifferent gonad development role 5 Estrogen, apoptosis regulation in germ cells 64, 65 Fas apoptosis regulation in germ cells Fertility preservation, see Infertility Fgf9, male sex differentiation role 15 Follicle-stimulating hormone apoptosis regulation in germ cells 63, 64 inhibin B level correlation 32 inhibin regulation 30, 31 -subunit 92, 93 receptor distribution in testes 86, 87 genes 85, 86 mutations activating mutations 95, 96 inactivating mutations overview 93, 94, 98 signal transduction 86 splice variants 86 structure spermatogenesis role 47 GATA, male sex differentiation role 14 Germ cell transplantation, fertility preservation in childhood testicular cancer 131, Germ cell tumors carcinoma in situ 111, 112 gonadoblastoma 112, 113 management adolescent germ cell tumors 118 infantile germ cell tumors 118 overt tumors 110, 111 Gonadoblastoma, features 112, 113 Gonadotropin-releasing hormone cryptorchidism management 107, 108 gonadotropin regulation 88, 89 Growth, testes 24, 43 Heat shock proteins, apoptosis regulation in germ cells 60 Human chorionic gonadotrophin cryptorchidism management 107, 108 half-life 82 -subunit 92 Immunological properties, testes 32 Indifferent gonad cell types and development connective cells 9 germ cells 9, 10 steroidogenic cells 8, 9 Subject Index 157

3 Indifferent gonad (continued) cell types and development (continued) supporting cells 6 8 genes in formation 3 5 overview of development 3 Infertility fertility preservation in childhood testicular cancer chemotherapy protective agents 131 ethics 150, 151 germ cell maturation in vitro germ cell transplantation 131, overview 129, 130, 141, 142 prospects 131, 132 semen cryopreservation 130, 139 testicular tissue cryopreservation 130, 149 germ line preservation vs fertility preservation 140 intracytoplasmic sperm injection development of technique 144 efficacy 145 oocyte calcium oscillations 144, 145 principles prevalence 136 sperm count reduction trends 140, 141 sperm requirements for assisted reproduction technologies 139 time span of fertile period 136 Inhibins assay of inhibin B 31 clinical uses 31, 32 function 30 levels in development 31, 32 regulation 30, 31 structures 30 Insulin-like hormone 3, cryptorchidism mutations 105 Interleukin-1, spermatogenesis role 48 Intracytoplasmic sperm injection development of technique 144 efficacy 145 oocyte calcium oscillations 144, 145 principles Leydig cell developmental changes in number 26 failure chemotherapy 127 radiation therapy 127, 128 origins 8, 9 pubertal changes 43 testosterone secretion, see Testosterone tumors 114, 119 types 26 Lhx9, male sex differentiation role 15 Lim1, indifferent gonad development role 5 Luteinizing hormone apoptosis regulation in germ cells 63 -subunit receptor structure genes 85, 86 signal transduction 86 splice variants 86 distribution in testes 86, 87 mutations activating mutations 94 inactivating mutations 94, 95 overview 93, 94, 98 spermatogenesis role 47 testosterone response 30 M33, indifferent gonad development role 5 Macrophage, interstitial functions 26 Mast cell, interstitial cells 26 Neural cell adhesion molecule, structural organization of testes 11 Nuclear factor- B anti-inflammatory drug inhibition 69 germ cell apoptosis role 68 p53 apoptosis regulation in germ cells 60, 72, 73 Subject Index 158

4 Primordial germ cell adhesion molecules 11 differentiation 13, 14, 39, 40 migration and proliferation 9, 10, 39, 40 Radiation therapy fertility preservation, see Infertility germ cell loss Leydig cell failure 127, 128 Reactive oxygen species, generation in germ cell apoptosis 71, 72 Seminiferous tubules germ cells 27, 28 peritubular myoid cells 27 Sertoli cells 28 Sertoli cell anti-müllerian hormone secretion 10, 38 blood-testis barrier 28, 29 differentiation 11 function 28 prepubertal spermatogenesis role 42, 43 pubertal changes 43 supporting cell lineage 6, 24 tumors 114, 115, 119 SF-1, indifferent gonad development role 3, 4 SMC proteins, spermatogenesis role 50 SOX9 collagen gene activation 12 testes development role 7 Spermatogenesis DNA methylation and genomic imprinting 147 duration of process 45 fetal period 39, 40 germ cell maturation in vitro infancy and childhood overview 27, 28, 38, 138 prepubertal testes 42, 43 puberty and adulthood 43 45, 47 regulation autosomal genes 49, 50 growth and differentiation factors 48 hormones 47, 48 sex chromosome genes 48, 49 Spermatogonia apoptosis 45, 61, 62 types 43, 44 SRY mouse development studies 6 positional cloning 6 protein function 6 testes differentiation role 1, 16 Temperature, testes 29 Testicular cancer cryptorchidism association 106, 107, 117, 118 diagnosis and management in children adolescent germ cell tumors 118 biopsy 117, 118 infantile germ cell tumors 118 intersex syndrome 118 stromal testicular tumors 119 epidemiology 116, 117, 141, 142 fertility preservation in children, see Infertility germ cell tumors carcinoma in situ 111, 112 gonadoblastoma 112, 113 overt tumors 110, 111 pathogenesis 117 prognosis of childhood cancer 124 side effects of treatment in children fertility outcomes 128 germ cell loss chemotherapy 125 overview 124, 125 radiation therapy gonadotropin deficiency 128 Leydig cell failure chemotherapy 127 radiation therapy 127, 128 offspring effects 129 psychosexual development impairment 128 stromal testicular tumors in children Leydig cell tumors 114, 119 markers 113, 114 Sertoli cell tumors 114, 115, 119 Subject Index 159

5 Testicular descent, see Cryptorchidism Testosterone apoptosis regulation in germ cells 63 androgen substitution 137, 138 gonadotrophin control of secretion 30 spermatogenesis role 47, 48 Thyroid hormone, spermatogenesis role 48 Tumor necrosis factor- receptor apoptosis regulation in germ cells Vanin-1, male sex differentiation role 15 Vitamin A, spermatogenesis role 48 WNT4, testes development role 8 WT1 indifferent gonad development role 3 5 isoforms 5 XH2, male sex differentiation role 14 Subject Index 160