55 Acrosome Membrane 34 Adenomyosis 115, 127 Adipocytes

Cambridge University Press 978-1-107-03447-1 - Stem Cells in Reproductive Medicine: Basic Science and Therapeutic Potential: Third Edition Edited by Carlos Simón, Antonio Pellicer and Renee Reijo Pera Index More information

Index

Locators in italic refer to figures and tables

a6 integrin (CD49f) 55 animal studies B-cells 81, 142 acrosome membrane 34 amniotic-fluid-derived stem cells Beckwith–Wiedemann syndrome 109, 110 37 adenomyosis 115, 127 bone-marrow-derived stem cells 125 adipocytes 105, 105–106 endometrial stem cells 121–122 beta-catenin 6,9 fetal surgery 134, 134–135, 136 beta1 integrin (CD29) 55 adult stem cells. See induced gamete generation 94 pluripotent stem cells See also mouse models bFGF growth factor 128 Advanced Cell Technology, Inc. 84 annexin-V-positive cells 38 bipolar disease 37 AFSC. See amniotic fluid-derived stem antigen-specific tolerance, in utero 133 blastocysts 84, 152 cells anti-Mullerian¨ hormone (AMH) 18 blastomeres age, maternal biopsy technique 84–85, linkage analysis 68–69 antimycin 167 86–88 non-disjunction 72 anti-oxidants 168, 169 cell autonomy 80, 81 AICAR (5-aminoimidazole gene expression 78 artificial insemination from viability diagnosis 79–80 carboxamide riboside) 173–174 anonymous donors (AID) 32, AID. See artificial insemination from 31–32, 32, 33,33 BLIMP1 gene expression 3, 16 anonymous donors Ascl1 (achaete-scute homolog 1) blood metastases 59 alkaline phosphatase (AP) 104 transcription factors 157 blood regeneration 110–111 allogeneic bone-marrow transfer 99 ascorbic acid 168 bone-marrow-derived stem cells alpha-MEM culture media 48 As model of stem-cell self-renewal 53, 124–125 54 Alzheimer’s disease 158 bone-marrow stroma 140, 143–144. assisted reproductive techniques See also mesenchymal stem ¨ AMH (anti-Mullerian hormone) 18 (ART) 15 cells amino acids 168, 172 ethics 95 bone morphogenetic protein 2 2, amniocentesis 103 sperm donation 32, 33 2–3 amniotic fluid-derived stem cells asthenozoospermia 35 bone morphogenetic protein 4 1, 2, 16, (AFSC) 102, 111–112 ATP metabolism 164–165, 172 52 characterization 104, 103–104, 105 authentic infertility, ethics 97 bone morphogenetic protein 7 clinical applications 108, 107–108, 105 108, 110, 111, 111 autism 37 bone morphogenetic protein 8B 1, 2, multipotency 105, 104–105, autoimmune disease 146 107 16, 52 See also gestational stem cells autologous reimplantation 103 bone regeneration 107, 108 amniotic sac 102 autosomal recessive osteoporosis, fetal brain tissue. See neuronal cells surgery 134–136 AMP-activated protein-kinase breast cancer resistance protein (AMPK) 173–174 azoospermia 34 (BCRP) 119 anemia, fetal surgery 134–136 BAF chromatin-remodeling complex bromodeoxyuridine (BrdU) label 115, Angelman syndrome 37 158 116, 117–118 animal cloning experiments Baf60c 158 Bub (Budding uninhibited by benzimidazole) proteins 23 152 bare lymphocyte syndrome 134

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© in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-1-107-03447-1 - Stem Cells in Reproductive Medicine: Basic Science and Therapeutic Potential: Third Edition Edited by Carlos Simón, Antonio Pellicer and Renee Reijo Pera Index More information

Index

cancer, epigenetics 37 clinical trials, hESCs 84 diakinesis/MI meiocytes 66 cancer patients colitis 146 differentiation, pluripotent cells blood metastases 59 collagen-induced arthritis 146 167–169 cryopreservation of testis 49–50 diplotene meiotic stage 23 fertility restoration 58, 57–58, 59 colony-forming units (CFUs) 117, spermatogonial stem cells 36 118–119, 126–127 direct lineage conversion. See transdifferentiation cancer stem cells (CSCs) 125–126 competitive advantage of fetal surgery 135 DNA integrity, spermatozoa 37–38 CAR cells (CXCL12-rich cells) 143, 144 COX gene expression 172 DNA methylation 37. See also cardiac cells 105, 159 crossover-associated proteins 67, 68,68 epigenetics cardiac transcription factors 158 cryopreservation of spermatogonial DNA polymorphisms 65–66 CD29 55 stem cells/testis 36, 49–50, 57, dogs, fetal surgery 135 CD30 172 58 Dolly the sheep 152 CD31 106 CTNNB1 (beta-catenin) 6,9 donor-recipient HLA matching 103 + CD45 bone-marrow cells 125 culture environments 170–173 donor-specific tolerance 133–134 CD49f (a6 integrin) 55 CXCL12 (chemokine (C-X-C motif) fetal surgery 136 CD133 55, 126 ligand 12) 4–5, 6, 143, 144 graft rejection 99 CD146 115, 122–124, 143 CXCR4 (chemokine (C-X-C motif) dopamine 143 receptor 4) 4–5, 6, 143, 144 CDH1. See E-cadherin dopaminergic neuron conversions 157 CYP26B1 (cytochrome P450 enzyme) double-strand breaks (DSBs) 64, 64–65 cell autonomy, blastomeres 80, 81 6,8 DPPA3. See STELLA cell cloning studies, endometrial stem cytochrome P450 18, 110 cells 117, 118–119 Drosophila cytokines 141 cell cycle controls 78 Hox gene 156 cytological analysis 66, 68, 67–68, stem-cell niches 54, 55–56 cell fusion, reprogramming 154 70–71 cell potency changes 153–154, 155 cytoplasmic endonucelase 24 E-cadherin 4–5,6 cell-based gene therapy 111 ectoderm cells 157, 164 DAX1 (nuclear receptor subfamily 0, ectopic tissue grafting 58–59 cell-of-origin memory 160–161 group B, member 1) 9–10 EGF growth factor 128 Centre d’Etude du Polymorphisme DAZ gene function 18, 22, 26 Humain (CEPH) 68 egg donation 15 DAZL (deleted in azoospermia-like) 5 centromere mapping 66,67 electron transport chain (ETC) 165 DDX4 (DEAD (Asp-Glu-Ala-Asp) box Chediak–Higashi syndrome 136 polypeptide 4) 5 embryo development and reprogramming 76 chemokines 141. See also CXCL12; DEAD-box gene family 26 CXCR4 imaging data 78–80, 81 dedifferentiation 154–156 and induced pluripotency 76–77 chiasmata, cytological analysis 66, definitions 154 novel analytic tools 81 67–68 default developmental path 8 oocyte-to-embryo transition 77–78 chimerism 124, 134 definitions embryo, moral status 95. See also ethics chondrocytes 106 azoospermia 34 embryo viability chromatin-modifying drugs 161 germ cells 1 and blastomere biopsy 86 chromatin remodeling 16, 17, 37 lineage conversion 154 prediction/diagnosis 79–80 niches 55 embryoid bodies (EBs) 20 chromatin-remodeling complex 157, pluripotency 164 158 transdifferentiation 154 embryonic stage-specific patterns (ESSPs) 80, 81 chromosome content, STCs 37 dendritic cells 141 chromosome number errors 63 embryonic stem cells (ESCs) 15, 36 desmosome-gap junction complexes 55 blastomere biopsy technique 84–85, chromosome 17, linkage analysis 69 developmental pluripotency-associated 86–88 chronic granulomatous disease 136 3. See STELLA cell cycle controls 78 diabetes mellitus 37 culture environment 170–173 c-kit membrane receptor 4, 6, 103, 124 developmental potency 152

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embryonic stem cells (ESCs) (cont.) factor VIII (FVIII) 106 genetic mapping techniques 66, 65–66, differentiation 21,22 female germline formation, PGCs 8, 68 energy metabolism 170 18. See also germline genetic status, SSCs 37 ethics 93, 94–97, 98, 99 development metabolic frameworks 166–174 genetically enhanced children 97 parthenote 85 fertility restoration, testicular SSCs 58, genome-wide analysis 120 57–58, 59 endoderm cells 157, 159, 164 genomics, massive analysis of sperm fetal bovine serum (FBS) 48 endometrial cancer 115, 125–126 39–40 fetal development, testicular SSCs GEO (Gene Expression Omnibus) endometrial regenerative capacity 52–53 115–116 database 120 fetal stem cells, remnant 124 endometrial stem/progenitor cells 115, germ-cell licensing 23 117–118, 127–128 fetal surgery 133–134, 136 germ-cell nuclear antigen 1 (GCNA1) characterization 116–117 animal studies 134–135, 136 5 clinical applications 125–127 clinical applications 134, 136 in vivo reconstitution 121–122 graft rejection 135–136 germ cells, definitions 1 markers 122–124 FGF9 (fibroblast growth factor 9) 6, germline development 15, 17, 26 menstrual blood 124 7–8 current challenges 22–26 mesenchymal stromal/stem cells in vitro generation 21, 20–21, 22 118–119, 120 fluorescence in situ hybridization mammals 16, 17, 16–17, 19 (FISH) 67 progenitor cell hypothesis 116, Geron, clinical trials 84 117–118 fluorescence-activated cell sorting side population cells 120, 121, (FACS) 46, 103 gestational stem cells 102–103, 111–112. See also amniotic 119–121, 123 FOLLISTATIN gene 8 sources 124–125 fluid-derived stem cells forkhead box L2 (FOXL2) 6,9 endometriosis 115, 126–127 GFAP+integrin ␤8+ 144 FRAGILIS gene 2,3,4,17 endothelial cells 105, 106 GFP (green fluorescent protein) 20, 54, FRIZZLED gene 8 125 energy metabolism, reprogramming 169–170 FST gene 6 GFP transgenes 47–48 epigenetic landscape model 154, GFP-negative ES cells 86 155, 156, 160–161 G1 and G2 cell cycle checkpoints 103, 104, 105 GFR␣1spermatogonialmarkers55 epigenetic memory 160–161 GABAergic transdifferentiation global decline in semen quality epigenetics 157 33–34 germline development 17, 17–19, gamete donation, ethics of 93. See 26 also ethics globozoospermia 35,35 spermatogenic cells 30 gamete generation glutamatergic transdifferentiation STCs 37 embryonic stem cells 94–97 157 erythroid cells 110–111 epigenetics 37 glutamine 165, 171 ESCs. See embryonic stem cells iPS cells 93–94 glycolytic metabolism estrogen 115–116, 117, 128 Gata4 158 culture environment role 171, 172 gay/lesbian reproduction 96, 97 differentiation of pluripotent ethics 93, 97–98, 99–100 cells 168 adult stem cells/iPS cells GCNA1 (germ-cell nuclear antigen 1) embryonic stem cells 165 93–94 5 hypoxia-inducible factors 173 efficiency of pregnancy GDNF 46–47 iPSCs 165, 169 establishment 99 pluripotency maintenance 164–165 embryo destruction 98 gene expression ESCs 94–97 embryonic stage-specific patterns gonadal niche 22, 26 ESCs derived from blastomeres 9, 80, 81 gonocytes 17, 52 93, 98 oocyte-to-embryo transition 77–78 PGCs 1, 2 graft rejection 111 gamete donation 93 fetal surgery 135–136 experimental autoimmune gene regulators, neural development immune system 99 158 encephalomyelitis (EAE) 146 graft vs. host disease (GvHD) 133, 141, extra cellular acidification rate (ECAR) gene therapy 145–146 168 cell-based 111 transgenerational 59 grandparents, genetic 96

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granulocyte-colony stimulating factor ICM (inner cell mass) 84 infertility 15, 37 (G-CSF) 109 ICSI. See intracytoplasmatic sperm inflammatory diseases 111 green fluorescent protein (GFP) 20, 54, injection 125 informed consent 96 ID4 spermatogonial markers 55 GSH/GSSG ratio 168 inner cell mass (ICM) 84 idiopathic infertility 37 insurance for the newborn 98 H2BWT (H2B histone family member IFITM3 (FRAGILIS) 2,3,4,17 W testis-specific) 40 interferon-induced trans-membrane IL1␤ immunoregulation 141 (IFTM) family proteins 2, 4, 17. hairpin loops 24 immortality 164 See also FRAGILIS heart disease 107, 108 immune system intracytoplasmic sperm injection heat shock protein2A (Hsp2A) 39 fetal surgery 134, 135–136 (ICSI) 20, 30–31, 35 azoospermia 34 hematopoietic niches 135 graft rejection 99 regeneration 110–111 sperm defects 35 hematopoietic stem cells (HSCs) 46, sperm donation indications 32, 102, 104, 140, 145–146. See also immune tolerance, twins 133 31–32, 32, 33,33 bone-marrow stroma; fetal immunofluorescence technology 66, iPSCs. See induced pluripotent stem surgery 67 cells hematopoietic system 110–111 immunoregulatory properties IVF (in vitro fertilization) 31 hemophilia 136, 136 amniotic fluid-derived stem cells 111 DNA fragmentation 38 mesenchymal stem cells 141–142 hepatic disease 106, 159 multiple births 76 imprinting, SSCs 37 sperm donation indications 32, hepatocytes 106 31–32, 32, 33,33 in utero hematopoietic cell hESC. See embryonic stem cells transplantation (IUHCTx) 133. KDM5D 19 HIFs (hypoxia-inducible factors) 173, See also fetal surgery Ki-67 117 174 in vitro fertilization. See IVF kidney disease 107–109 high mobility group (HMG)-box in vitro germline development 21, family 7 20–21, 22 kinase insert domain receptor (KDR) 106 hiN (human induced-neuronal) cells in vitro models, dedifferentiation 156 158 KITL (Steel Factor) 4,6 in vitro spermatogenesis 46, 50 histone methylation 17–19, 37, 70. See cryopreservation 49–50 KnockoutTM Serum Replacement 48, also epigenetics organ culture method 47–48 172 Hodgkin’s disease 58, 57–58, 59 SSCs multiplication 46–47 label-retaining cells (LRCs) 118, Hoechst dye exclusion method in vitro spermatogonial 117–118, 119, 120 119–121 transplantation 46 lactate 168, 170 Homeobox (Hox) gene expression 3 in vitro survival/proliferation, laminin 87 homeostasis maintenance 164 testicular SSCs 56 lentiviruses 85 homosexual reproduction 96, 97 in vitro transdifferentiation 157 leptotene meiotic stage 23 hot spots of recombination 19 in vitro transplantation and culture method (IVTC method) 48–49 lesbian/gay reproduction 96, 97 Hox gene, Drosophila 156 in vivo reconstitution, endometrial leukemia 58, 57–58, 59 HSCs. See hematopoietic stem cells stem cells 121–122 leukocyte adhesion deficiency human embryo, moral status 95. See inbreeding 97 134–136 also ethics induced pluripotent stem cells (iPSCs) lineage conversion, definition 154. See human embryonic stem cells. See 15, 85, 152 also transdifferentiation embryonic stem cells amniotic fluid-derived 111 linkage analysis 66, 65–66, 69, 68–69, Human Genome Project 68 cell cycle controls 78 comparison with embryo 70 human induced-neuronal (hiN) cells development/reprogramming linkage disequilibrium (LD) mapping 158 76–77 66, 66–67 human-specific endothelial cell surface energy metabolism 169–170 lipids composition, spermatozoa marker (P1H12) 106 ethics 93–94 40 safety 85, 86 hypoxia-inducible factors (HIFs) 173, liver disease 106, 159 174 transdifferentiation 85–86 183

Index

lung disease 109–110, 111 clinical applications 144–146 bone regeneration 107, 108 lymphocytes 165 endometrial stem/progenitor cells cell pluripotency 160 118–119, 120 female germline formation 8 lymphoid cells 110–111 immunoregulatory properties germ-cell development in vivo 15 lymphoma, mouse model 156 141–142 germline development 20 markers 122–124, 126–128, 141 lymphoma 156 lysine demethylase (KDM5D) 19 properties 140–141 mitotic arrest 5–7 See also bone-marrow stroma PGC sex determination 5 macrophage migration inhibitory PGC specification 1 factor (MIF) 110 mesenchymal-to-epithelial transitions (MET) 156 regeneration of body parts, neonatal Mad (mitotic arrest deficient) proteins 153 23 mesoderm cells, transdifferentiation SOX9 7 157, 158–159, 164 male gamete. See spermatozoa SSCs 36 metabolic disorders, fetal surgery 136 transdifferentiation 159 male germline formation, PGCs 5–8, 18 metabolism, PSCs 164, 166–174, MSCs. See mesenchymal stem cells 175–176 malignant cells, removal 59 MSCI (meiotic sex chromosome culture environment 170–173 inactivation) 19 mammals differentiation 167–169 cellular regeneration 153, 154 energy metabolism 169–170 MSUC (meiotic silencing of unpaired germline development 16, 17, 16–17, molecular regulation 173–175 chromatin) 19 19 pluripotency maintenance 164–167 mTOR (rapamycin) 173–174, 175 markers mice. See mouse models mucin 39 AFSC 103–104 microarray technology 39 multidrug resistance protein (MDR1) endometrial cancer 126 119 ESC 122–124 microchimerism, maternal 134 MSC 122–124, 126–128, 141 microenvironments, testicular 47 multilineage differentiation, MSCs 119 testicular SSCs 55 Microrespiration System 39 multiple births, IVF 76 massive analysis, spermatozoa 39–40 micro-RNA (miRNA) 25, 23–25, 26, multiple sclerosis 146 maternal immune system, role in fetal 157 multipotency 152, 153 surgery 135–136 micro-seminoprotein beta 40 AFSC 105, 104–105, 107 maternal microchimerism 134 MiDReG (mining developmentally multipotent hematopoietic stem cells Mef2c 158 regulated genes) 81 102, 124, 145–146 meiosis, human oocytes 63, 68–70, 72 migration, PGCs 4, 3–5, 6, 16–18 multipotent MSCs. See mesenchymal crossover-associated proteins 68 stem cells cytological studies 68, 70–71 miRNA-induced silencing complex (miRISC) 24 Musashi-1 RNA-binding protein non-disjunction 71, 71, 72 123–124 recombination, measuring 66, mitochondria 65–66, 68, 68–70 differentiation of pluripotent cells muscular dystrophy 136, 136 recombination/crossovers 64, 64–65 168–169 Mvh (mouse VASA homologous) 20 as sexually dimorphic process 63–64 embryonic stem cells 165–167 myeloablation 133 iPS cells/ES cell comparison 170 meiosis induction myeloid cells 110–111 current challenges 22–23 metabolism. See oxidative germline development 19, 18–19 metabolism myoblast determination factor 156 meiosis, SSCs multiplication in vitro 47 mitochondrial membrane potential myocardial infarction (MI) 107, 108 (MMP) 165–167 meiotic sex chromosome inactivation myocytes 105, 105 mitotic arrest 5–7 (MSCI) 19 myometrium 120–121 meiotic silencing 18, 19 MLH1 crossover-associated proteins 67, 68, 69, 70–71 Myt1L transcription factors 157 memory, cell-of-origin 160–161 molecular regulation, PSMs 173–175 NADPH 165 menopause 116 moral status, human embryo 95. See NANOG 17, 159, 164, 173, 174–175 menstrual blood progenitor cells 124 also ethics NANOS2 (nanos homolog 2 mesenchymal stem cells (MSCs) 102, morula 102 (Drosophila)) expression 6,8 140, 145, 146 in bone-marrow stroma 143–144 mouse models National Survey on Family Growth 15 blastomere biopsy technique 86

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NCBI Gene Expression Omnibus osteogenesis imperfecta 134–136 piwi-interacting RNAs (piRNAs) 25, (GEO) database 120 oxidative metabolism 24–25 nestin 144 and culture environment 172, 173 placental membranes. See gestational neuronal cells pluripotency maintenance 164–165 stem cells AFSC 107, 109, 110 PSCs 166–169, 174 plasminogen activator inhibitor-1 gene regulators 158 oxidative phosphorylation (OXPHOS) (PAI-1) 110 transdifferentiation 157, 157–158, 165 plasticity, cellular 154 159 culture environment role 172 platelet-activating factor (PAF) 39 Neurospora crassa 67 differentiation of pluripotent cells 168 pluripotency 152 newts, regeneration of body parts 153 hypoxia-inducible factors 173 blastocysts 152 N-glycolylneuramine (Neu5Gc) 172 somatic cells 165 definitions 164 niches oxidative stress, and sperm defects 38. maintenance 164–167 hematopoietic 135 See also reactive oxygen species mouse cells 160 testicular SSCs 54, 55–56 testicular SSCs 56–57 oxygen concentration, culture See also germline development; non-disjunction, meiotic 71, 71, 72 environment 171, 173, 174 metabolism, PSCs non-inherited maternal antigens oxygen uptake, spermatozoa 39 post-menopausal women 97 (NIMAs) 133 endometrial cancer 126 P1H12 (human-specific endothelial giving birth, 97 non-medical applications, ethics 96–97 cell surface marker) 106 post-transcriptional gene regulation non-obstructive azoospermia (NOA) pachytene meiotic stage 23 34 23–26 PAI-1 (plasminogen activator Notch-1 123–124 POU class 5 homeobox 1 (POU5F1). inhibitor-1) 110 See Oct 4 NR0B1 (nuclear receptor subfamily 0, ␤ pancreatic insulin-producing -cells Prader–Willi syndrome 37 group B, member 1) 6,9–10 154, 159 PRDM1 2,3 NR5A1 (steroidogenic factor 1) 7 parenthood, determination of 95–96 PRDM9 70 nuclear reprogramming 154. See also parenthood, genetic 30 reprogramming ethicals 94 PRDM14 2,3 obstructive azoospermia (OA) 34 parthenote ESCs 85 pre-implantation diagnostics (PGD) 31, 86, 98 Oct 4 (POU5F1) 16, 17, 122–123, passive developmental path 8 primordial germ cells (PGCs) 1, 2, 158–159, 164 paternity, biological. See parenthood gene expression 54, 86 10 hypoxia-inducible factors 173 PDGF growth factor 128 ethics 93 spermatogonial markers 55 PDGF Receptor-␤ (PDGF-R␤) 115, female germline formation 8, 18 122–124 fetal development 52–53 ODFP2 (outer dense fiber protein 2) 40 male germline formation 5–8, oncogenes, safety 85 pelvic-floor prolapse 127 18 pentose phosphate pathway (PPP) 169 migration 3, 4–5, 6, 16–18 oocyte-like cells (OLCs) 20 sex determination 5, 5, 18–19 oocyte-to-embryo transition, gene peritubular myoid cells 55 specification 1, 2, 3, 16–18 expression 77–78. See also permissive chromatin mark 70 production line model of maternal age embryo development and PGCs. See primordial germ cells 68 reprogramming PGD (pre-implantation diagnostics) progenitor cell hypothesis 116, oocytes 31, 86, 98 117–118. See also endometrial atresia selection process 19 stem/progenitor cells parthenogenesis 85 phosphoglycerate kinase (PGK) 165 See also meiosis, human oocytes phosphoglyceromutase (PGM) 165 progesterone 128 oral contraceptive pills (OCP) 116 phosphorylated histone H3 (PH3) prophase cells, cytological analysis 67, 68,68 organ culture method, 117 spermatogenesis 47–48 physiology. See metabolism, PSCs prostaglandin D synthase (PTGDS) 6 ornithine decarboxylase antizyme 3 pigs, fetal surgery 135 prostaglandin D2 (PGD2) 6,7 (OAZ3) 40 ping-pong mechanism, piRNAs 25, proteomics, massive analysis of sperm osteocytes 104–105 24–25, 26 39–40

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proton gradients, mitochondrial SCF (stem cell factor) 103 SPATA7 (spermatogenesis-associated membrane potential 165 schizophrenia 37 gene 7) 40 PTGDS (prostaglandin D synthase) 6 Schwann cells 153 SPAT9 (spermatogenesis-associated protein 9) 40 public hESC banks 99 SCNT reprogramming 154, 160, 161 specification, PGCs 2, 1–2, 3, 16–18 pulmonary disease 109–110, 111 SDF1 (chemokine (C-X-C motif) ligand 12) 4–5, 6, 143, 144 sperm-associated antigen 5 (SPAG5) racial differences, linkage analysis 68 40 semen quality, global decline 33–34 rapamycin (mTOR) 173–174, 175 sperm chromatin structure assay Sertoli cells 47 (SCSA) 38 reactive oxygen species (ROS) 38, 173 differentiation 7, 18 recombination hot spots 70. See also fetal development 52–53 sperm counts 33–34. See also meiosis organ culture method 48 spermatozoa redox status 166–168, 174 sperm defects 34 spermatids 7 stem-cell niches 55 regenerative medicine 153 spermatocytes 7 AFSC 107–111 serum 172 spermatogenesis 19, 36 clinical applications 59, 84 severe combined immunodeficiency spermatogenesis-associated gene 7 safety 86 (SCID) 134, 136 (SPATA7) 40 See also ethics sex determination, PGCs 5, 5, 18–19 spermatogenesis-associated protein remnant fetal stem cells 124 sex determining region Y (SRY) 5, (SPAT9) 40 renal disease 107–109 7 spermatogonia 5 reproductive failure, sperm defects 30 sexual dimorphism, meiosis 63–64 spermatogonial stem cells (SSCs) reprogramming 152–153, 161 SF1 (steroidogenic factor 1) 7 35–36, 59 changing cell potency 153–154, 155 SGT (spermatogonial transplantation) chromosomal content 37 dedifferentiation 154–156 46, 57–58 clinical applications 59 energy metabolism 169–170 cryopreservation of SSCs/testis epigenetic memory 160–161 sheep, fetal surgery 135 49–50 iPSCs 85–86 sickle cell disease 134–136 epigenetics 37 transdifferentiation 157, 156–157, fertility restoration 58, 57–58, 160 side population (SP) cells 121, 59 120–121, 123 fetal development 52–53 retinoic acid (RA) 6, 7–8, 10, 18, 168, endometrial cancer 126 169 identity/characterization 53–55 endometrial stem cells 119–121 in vitro 46–47, 56. See also in vitro retro viruses 85 single nucleotide polymorphisms spermatogenesis ribosomal protein (RPS3A) 40 (SNPs) 65–66 markers 55 siRNAs 24 niches 54, 55–56 ring finger protein (RNF212) 69 pluripotency 56–57 RNA degradation, as active process 80 sirtuin-1 (SIRT1) pathway 173–175 self-renewal/differentiation balance RNA-binding proteins 25, 23–25, 26. SKD (suppressor of potassium 53, 54 See also micro-RNA transport defect) 40 spermatogonial transplantation (SGT) ROS (reactive oxygen species) 38, 173 SLE (systemic lupus erythematosus) 46, 57–58 146 R-sponsin 1 (RSPO1) 6,9 spermatozoa 7, 30, 35 small non-coding RNAs 25, 23–25, absent/failing 30–33 SAC (spindle assembly checkpoint) 23 26 characteristics from infertile men 33–35 Saccharomyces cerevisiae 23, 64 SMCY 19 defects 30, 33, 34–35, 46 S-adenosyl methionine (SAM) 170 somatic cell nuclear transfer (SCNT) DNA integrity 37–38 154, 160, 161 donation 32, 30–32, 32, 33,33 safety somatic cells massive analysis 39–40 gamete generation 94 membrane lipids 40 iPSCs 85, 86 electron transport chain 165 metabolism 166–174 molecular features of functional SALL4 gene expression 54 oxidative phosphorylation 165 36–40 same-sex reproduction 96, 97 TCA cycle 165 washing 31 savior siblings 98–99 SOX. See SRY box gene family spermiogenesis 19 SC. See synaptonemal complex SP. See side population cells spermiograms, WHO criteria 36

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spinal cord testicular SSCs. See spermatogonial uncoupling protein 2 (UCP2) 175 injury, clinical trials 84 stem cells unipotency 152 transdifferentiation 157 testicular tissue grafting 58–59 urodeles, regeneration of body parts spindle assembly checkpoint (SAC) 23 TGF␣ growth factor 128 153, 155–156 SRY (sex-determining region Y) 6,7,8 TH17 cells 142 urogynaecology 115 SRY-box gene family 2 (SOX2) 164, 173 thalassemia 134–136 VASA RNA-binding protein 26 SRY-box gene family 9 (SOX9) 6,7,18 THY1 markers 55 SSCs. See spermatogonial stem cells vascular cell adhesion molecule tissue banks 136 (VCAM) 106 SSEA4 spermatogonial marker 55 tissue engineering 115, 127 vascular diseases 106 Steinberger, A. and E. 47 tissue grafting 58–59 viability. See embryo viability STELLA gene expression 2,3,4,17 TLR stimulation of MSCs 142 viral vectors 85, 111 stem-cell factor (SCF) 103 TNF␣ immunoregulation 141 von Willebrand factor (vWF) steroidogenic factor 1 (SF1) 7 toposiomerase 23 106 STRA8 6, 55 totipotency 152 W5C5 marker 115, 122–124 Streptolysin-O 85 transcription factors 164 + Wake Forest Institute for Regenerative Stro-1 stromal cells 143. See also Ascl1 157 Medicine (WFIRM) 103 bone-marrow stroma Brn2 157 website, www.geron.com 84 stromal stem cells 118–119 Myt1L 157 nuclear reprogramming 154 WHO (World Health Organization) suppressor of potassium transport guidelines 34, 36 defect (SKD) 40 transcription profiling, oocytes 77–78 WNT (wingless-related MMTV synapsis 18 transdifferentiation 156–160 definitions 154 integration site) 6,8–9 synaptonemal complex (SC) 18, 23, 64, in vitro 157 Wnt7a gene expression 116 65, 67 iPSCs 85–86 wound repair 111 systemic lupus erythematosus (SLE) transforming growth factor-␤ (TGF-␤) 146 1 xeno-free systems 172 Tbx5 158 transgenerational gene therapy 59 xeno-transplantation experiments 46 TCA cycle 165, 169 transplantation tolerance, fetal 136. See also graft rejection; graft vs. T cells, immunoregulation 142 host disease Y chromosome microdeletions 37 t-complex-associated-testis- tricarboxylic acid (TCA) cycle 165, 169 expressed-1 40 Yamanaka cocktail 159 trisomies, human 71, 71, 72 telomerase activity 103, 104 yeast cells 23, 64 TSPY1 spermatogonial markers 55 endometrial stem cells 123–124 yuck factor 96 menstrual blood 124 tumor cells, metabolism 165 teratozoospermia 34 tumorigenesis 153 Zgene8 TESCO (testis-specific enhancer of twins, immune tolerance 133 zebrafish, regeneration of body parts Sox9 core) 7 twitcher mouse model of neurological 153, 155 testes disease 109, 110 zinc finger protein PRDM9 70 cryopreservation 49–50 zygote totipotency 152 tissue grafting 58–59 ubiquitin 39 zygotene meiotic stage 23 testicular sperm extraction (TESE) 34 umbilical-cord-blood banking 98

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