About the EditorsHeide Schatten Department of Veterinary Pathobiology, University of Missouri-Columbia, Columbia, USAGheorghe M. Constantinescu Department of Biomedical Sciences, University of Missouri-Columbia, Columbia, USA

• List of Contributors xv1 Anatomy of the Reproductive System 1Gheorghe M. Constantinescu1.1 Male Genital Organs in Domestic Mammals 11.2 Female Genital Organs in Domestic Mammals 51.3 The Genital System in Domestic Mammals Species by Species 91.4 Genital Organs in Laboratory Mammals 35References 562 Anatomy of Mammalian (Endocrine) Glands Controlling the Reproduction 59Gheorghe M. Constantinescu2.1 The Hypothalamus Including the Hypophysis 592.2 The Cerebral Epiphysis 612.3 The Thyroid Gland 612.4 The Adrenal Glands 622.5 The Sexual Glands 632.6 The Liver 63References 633 Models for Investigating Placental Biology 65Laramie Pence and Bhanu P. Telugu3.1 Introduction 653.2 Classification of Placenta 663.3 Development of Human Placenta 693.4 Modeling Placental Development and Diseases of Placental Origin 733.5 Summary 82References 824 Early Developmental Programming of the Ovarian Reserve, Ovarian Function, and Fertility 91Francesca Mossa, Siobhàn W. Walsh, Alex C.O. Evans, Fermin Jimenez-Krassel, and James J. Ireland4.1 Introduction 914.2 Impact of Prenatal Environmental Challenges on Fetal Oogonia (Germ Cells) 924.3 Impact of Prenatal Environmental Challenges on Fetal Follicle/Oocyte Numbers (Healthy versus Atretic) and Oocyte Quality 944.4 Impact of Prenatal Environmental Challenges on the Ovarian Reserve (Total Number of Morphologically Healthy Follicles/Oocytes in Ovaries) in Offspring 954.5 Impact of Prenatal Environmental Challenges on Ovarian Function (e.g., Pituitary Gonadotropin Secretion, Ovarian Hormone/Growth Factor Production, Response to Gonadotropins, Follicle Development, Irregular Reproductive Cycles, and Ovulation Rate) in Offspring 984.6 Impact of Prenatal Environmental Challenges on Fertility (as Measured by Conception Rates, Fecundity, or Age at Puberty or Menopause) in Offspring 1004.7 Summary and Conclusion 101References 1025 Small Non-Coding RNAS in Gametogenesis 109Lukasz Smorag and D. V. Krishna Pantakani5.1 Small Non-Coding RNAs 1095.2 Function of sncRNAs in Gametogenesis 109Acknowledgment 119References 1196 The Ovarian Follicle of Cows as a Model for Human 127Marc-André Sirard6.1 Introduction 1276.2 A Similar Physiology of Folliculogenesis 1286.3 Assisted Reproduction 1316.4 Testing the Competence Hypothesis 1366.5 Conclusion 136References 1367 Production of Energy and Determination of Competence: Past Knowledge, Present Research, and Future Opportunities in Oocyte and Embryo Metabolism 145Jason R. Herrick, Elena Silva, and Rebecca L. Krisher7.1 Introduction 1457.2 Measuring Metabolism 1457.3 The Relationship Between Oocyte Metabolism and Quality 1487.4 Embryo Metabolism 1527.5 Metabolic Biomarkers 1577.6 Toward Personalized Culture Media: Formulating Media for Specific Maternal Conditions 1587.7 Summary 161References 1628 Signal Transduction Pathways in Oocyte Maturation 177François J. Richard, Nicolas Santiquet, Annick Bergeron, and Daulat Raheem Khan8.1 Introduction 1778.2 Phosphodiesterase 1818.3 Gap Junction Communications 1928.4 Metabolic Switch (AMPK) 1938.5 Conclusion 198References 1989 Pig Models of Reproduction 213B.R. Mordhorst and R.S. Prather9.1 Introduction 2139.2 Early Embryonic Development 2139.3 Oocyte Maturation 2159.4 Fertilization 2169.5 Tubouterine Contractility 2169.6 Development to the Blastocyst Stage 2169.7 Pregnancy and Developmental Programming 2179.8 Puberty 2229.9 Reproductive Disease 2239.10 Summary 223Acknowledgments 223References 22310 The Mare as an Animal Model for Reproductive Aging in the Woman 235Elaine M. Carnevale10.1 Introduction 23510.2 Ovarian Activity and Reproductive Cycles 23610.3 The Follicle 23810.4 Fertility 23910.5 The Oocyte 24010.6 Conclusions 242References 24211 Spotlight on Reproduction in Domestic Dogs as a Model for Human Reproduction 247Shirley J. Wright11.1 Introduction 24711.2 Dog Reproduction 25511.3 Dog-Assisted Reproductive Technology 32111.4 Dog Contraception 32811.5 The Dog as a Model for Human Reproduction 32811.6 Concluding Statements 332Acknowledgments 333References 33312 Animal Models of Inflammation During Pregnancy 359Karen E. Racicot and Keith E. Latham12.1 Introduction 35912.2 Local Inflammation of the Pregnant Female Reproductive Tract 36012.3 Systemic Inflammation During Pregnancy 36112.4 Genetic Models and Cellular Manipulation to Study Inflammation During Pregnancy 36512.5 Inflammation During Pregnancy and Offspring Disease 37012.6 Perspectives and Conclusions 372Acknowledgments 373References 37313 Practical Approaches, Achievements, and Perspectives in the Study on Signal Transduction in Oocyte Maturation and Fertilization: Focusing on the African Clawed Frog Xenopus laevisas an Animal Model 383Ken-ichi Sato13.1 Introduction to Reproductive Biology of Frog Oocytes and Eggs 38313.2 Practical Approaches 38313.3 Achievements and Perspectives 395Acknowledgments 396Appendix 396References 39914 Prezygotic Chromosomal Examination of Mouse Spermatozoa 401Hiroyuki Watanabe and Hiroyuki Tateno14.1 Introduction 40114.2 Procedure of Sperm Chromosome Screening 40214.3 Practical Use of SCS Before Fertilization 40414.4 Conclusion 406Acknowledgments 406Addendum 406References 40615 Molecular and Cellular Aspects of Mammalian Sperm Acrosomal Exocytosis 409Florenza A. La Spina, Cintia Stival, Dario Krapf, and Mariano G. Buffone15.1 Introduction 40915.2 Structure of the Acrosome 40915.3 Intermediate Stages of Exocytosis 41215.4 Sperm Capacitation Prepare the Sperm to Undergo Acrosomal Exocytosis 41215.5 Physiological Site for the Occurrence of Acrosomal Exocytosis 41415.6 SNARES and Other Proteins from the Fusion Machinery 41615.7 Hyperpolarization 41715.8 Actin Cytoskeleton 41715.9 Calcium 418References 41916 Sperm Chromatin Dynamics Associated with Male Fertility in Mammals 427Naseer A. Kutchy, Sule Dogan, Abdullah Kaya, Arlindo Moura, and Erdogan Memili16.1 Introduction 42716.2 Sperm Chromatin Structure Modulates Sperm Nuclear Shape and Function 42916.3 The Bull Is a Suitable Model for the Study of Male Fertility in Humans 43016.4 Conclusions and Prospects 430Acknowledgments 431References 43117 Epigenome Modification and Ubiquitin-Dependent Proteolysis During Pronuclear Development of the Mammalian Zygote: Animal Models to Study Pronuclear Development 435Jan Nevoral and Peter Sutovsky17.1 Introduction 43517.2 Milestones of Pronuclear Development 43617.3 Nuclear Envelope, Nuclear Pore Complexes, and Nuclear Lamina Changes During Pronuclear Development 43817.4 Molecular Mechanism of Paternal and Maternal Pronucleus Biogenesis 44017.5 Role of UPS in Pronuclear Biogenesis 44217.6 Posttranslational Modifications of Pronuclear Histones 44317.7 Sirtuin Family Histone Deacetylases in Gametogenesis and Development 44617.8 Clinical and Technological Considerations 44717.9 Conclusions 450Acknowledgments 450References 45018 Alterations of the Epigenome Induced by the Environment in Reproduction 467Zhao-Jia Ge, Shen Yin, and Heide Schatten18.1 Introduction 46718.2 Epigenetic Reprogramming 46718.3 Environment and Epigenetic Alterations 47018.4 Animal Models Used in Reproduction to Research Epigenetic Alterations Induced by the Environment 47218.5 Effects of Environment on Epigenetic Modifications in Humans 47518.6 Epigenetics and Assisted Reproductive Technology (ART) 47518.7 Priorities for the Future 476Acknowledgments 476References 47619 Toward Development of Pluripotent Porcine Stem Cells by Road Mapping Early Embryonic Development 485Stoyan Petkov, Kristine Freude, Kaveh Mashayekhi, Poul Hyttel, and Vanessa Hall19.1 Introduction 48519.2 Current Status on the Pluripotent State in the Pig Embryo 48919.3 Current Status of the Establishment of Porcine Embryonic Stem Cells (pESCs) 49119.4 Current Status in Establishment of Porcine-Induced Pluripotent Stem Cells 49419.5 Future Perspectives: Use of Global Profiling on Pluripotent Cells from Pig Embryo and Pluripotent Stem Cells 49919.6 Discussion and Conclusions 501Acknowledgments 502References 50220 Applications of Metabolomics in Reproductive Biology 509Ana Luiza Cazaux Velho, Rodrigo Oliveira, Thu Dinh, Arlindo Moura, Abdullah Kaya, and Erdogan Memili20.1 Introduction 50920.2 Metabolomics and Reproductive Biology 51020.3 Metabolomics Studies in Large Animals as Models for Humans 51320.4 Conclusions and Future Prospects 513Acknowledgments 514Conflict of Interest 514References 51421 Cryopreservation of Mammalian Oocytes 519Muhammad Anzar21.1 Principles of Cryopreservation 51921.2 Cryopreservation of Mammalian Oocytes 522Acknowledgments 542Abbreviations 543References 543Index 557

About the EditorsHeide Schatten Department of Veterinary Pathobiology, University of Missouri-Columbia, Columbia, USAGheorghe M. Constantinescu Department of Biomedical Sciences, University of Missouri-Columbia, Columbia, USA

• List of Contributors xv1 Anatomy of the Reproductive System 1Gheorghe M. Constantinescu1.1 Male Genital Organs in Domestic Mammals 11.2 Female Genital Organs in Domestic Mammals 51.3 The Genital System in Domestic Mammals Species by Species 91.4 Genital Organs in Laboratory Mammals 35References 562 Anatomy of Mammalian (Endocrine) Glands Controlling the Reproduction 59Gheorghe M. Constantinescu2.1 The Hypothalamus Including the Hypophysis 592.2 The Cerebral Epiphysis 612.3 The Thyroid Gland 612.4 The Adrenal Glands 622.5 The Sexual Glands 632.6 The Liver 63References 633 Models for Investigating Placental Biology 65Laramie Pence and Bhanu P. Telugu3.1 Introduction 653.2 Classification of Placenta 663.3 Development of Human Placenta 693.4 Modeling Placental Development and Diseases of Placental Origin 733.5 Summary 82References 824 Early Developmental Programming of the Ovarian Reserve, Ovarian Function, and Fertility 91Francesca Mossa, Siobhàn W. Walsh, Alex C.O. Evans, Fermin Jimenez-Krassel, and James J. Ireland4.1 Introduction 914.2 Impact of Prenatal Environmental Challenges on Fetal Oogonia (Germ Cells) 924.3 Impact of Prenatal Environmental Challenges on Fetal Follicle/Oocyte Numbers (Healthy versus Atretic) and Oocyte Quality 944.4 Impact of Prenatal Environmental Challenges on the Ovarian Reserve (Total Number of Morphologically Healthy Follicles/Oocytes in Ovaries) in Offspring 954.5 Impact of Prenatal Environmental Challenges on Ovarian Function (e.g., Pituitary Gonadotropin Secretion, Ovarian Hormone/Growth Factor Production, Response to Gonadotropins, Follicle Development, Irregular Reproductive Cycles, and Ovulation Rate) in Offspring 984.6 Impact of Prenatal Environmental Challenges on Fertility (as Measured by Conception Rates, Fecundity, or Age at Puberty or Menopause) in Offspring 1004.7 Summary and Conclusion 101References 1025 Small Non-Coding RNAS in Gametogenesis 109Lukasz Smorag and D. V. Krishna Pantakani5.1 Small Non-Coding RNAs 1095.2 Function of sncRNAs in Gametogenesis 109Acknowledgment 119References 1196 The Ovarian Follicle of Cows as a Model for Human 127Marc-André Sirard6.1 Introduction 1276.2 A Similar Physiology of Folliculogenesis 1286.3 Assisted Reproduction 1316.4 Testing the Competence Hypothesis 1366.5 Conclusion 136References 1367 Production of Energy and Determination of Competence: Past Knowledge, Present Research, and Future Opportunities in Oocyte and Embryo Metabolism 145Jason R. Herrick, Elena Silva, and Rebecca L. Krisher7.1 Introduction 1457.2 Measuring Metabolism 1457.3 The Relationship Between Oocyte Metabolism and Quality 1487.4 Embryo Metabolism 1527.5 Metabolic Biomarkers 1577.6 Toward Personalized Culture Media: Formulating Media for Specific Maternal Conditions 1587.7 Summary 161References 1628 Signal Transduction Pathways in Oocyte Maturation 177François J. Richard, Nicolas Santiquet, Annick Bergeron, and Daulat Raheem Khan8.1 Introduction 1778.2 Phosphodiesterase 1818.3 Gap Junction Communications 1928.4 Metabolic Switch (AMPK) 1938.5 Conclusion 198References 1989 Pig Models of Reproduction 213B.R. Mordhorst and R.S. Prather9.1 Introduction 2139.2 Early Embryonic Development 2139.3 Oocyte Maturation 2159.4 Fertilization 2169.5 Tubouterine Contractility 2169.6 Development to the Blastocyst Stage 2169.7 Pregnancy and Developmental Programming 2179.8 Puberty 2229.9 Reproductive Disease 2239.10 Summary 223Acknowledgments 223References 22310 The Mare as an Animal Model for Reproductive Aging in the Woman 235Elaine M. Carnevale10.1 Introduction 23510.2 Ovarian Activity and Reproductive Cycles 23610.3 The Follicle 23810.4 Fertility 23910.5 The Oocyte 24010.6 Conclusions 242References 24211 Spotlight on Reproduction in Domestic Dogs as a Model for Human Reproduction 247Shirley J. Wright11.1 Introduction 24711.2 Dog Reproduction 25511.3 Dog-Assisted Reproductive Technology 32111.4 Dog Contraception 32811.5 The Dog as a Model for Human Reproduction 32811.6 Concluding Statements 332Acknowledgments 333References 33312 Animal Models of Inflammation During Pregnancy 359Karen E. Racicot and Keith E. Latham12.1 Introduction 35912.2 Local Inflammation of the Pregnant Female Reproductive Tract 36012.3 Systemic Inflammation During Pregnancy 36112.4 Genetic Models and Cellular Manipulation to Study Inflammation During Pregnancy 36512.5 Inflammation During Pregnancy and Offspring Disease 37012.6 Perspectives and Conclusions 372Acknowledgments 373References 37313 Practical Approaches, Achievements, and Perspectives in the Study on Signal Transduction in Oocyte Maturation and Fertilization: Focusing on the African Clawed Frog Xenopus laevisas an Animal Model 383Ken-ichi Sato13.1 Introduction to Reproductive Biology of Frog Oocytes and Eggs 38313.2 Practical Approaches 38313.3 Achievements and Perspectives 395Acknowledgments 396Appendix 396References 39914 Prezygotic Chromosomal Examination of Mouse Spermatozoa 401Hiroyuki Watanabe and Hiroyuki Tateno14.1 Introduction 40114.2 Procedure of Sperm Chromosome Screening 40214.3 Practical Use of SCS Before Fertilization 40414.4 Conclusion 406Acknowledgments 406Addendum 406References 40615 Molecular and Cellular Aspects of Mammalian Sperm Acrosomal Exocytosis 409Florenza A. La Spina, Cintia Stival, Dario Krapf, and Mariano G. Buffone15.1 Introduction 40915.2 Structure of the Acrosome 40915.3 Intermediate Stages of Exocytosis 41215.4 Sperm Capacitation Prepare the Sperm to Undergo Acrosomal Exocytosis 41215.5 Physiological Site for the Occurrence of Acrosomal Exocytosis 41415.6 SNARES and Other Proteins from the Fusion Machinery 41615.7 Hyperpolarization 41715.8 Actin Cytoskeleton 41715.9 Calcium 418References 41916 Sperm Chromatin Dynamics Associated with Male Fertility in Mammals 427Naseer A. Kutchy, Sule Dogan, Abdullah Kaya, Arlindo Moura, and Erdogan Memili16.1 Introduction 42716.2 Sperm Chromatin Structure Modulates Sperm Nuclear Shape and Function 42916.3 The Bull Is a Suitable Model for the Study of Male Fertility in Humans 43016.4 Conclusions and Prospects 430Acknowledgments 431References 43117 Epigenome Modification and Ubiquitin-Dependent Proteolysis During Pronuclear Development of the Mammalian Zygote: Animal Models to Study Pronuclear Development 435Jan Nevoral and Peter Sutovsky17.1 Introduction 43517.2 Milestones of Pronuclear Development 43617.3 Nuclear Envelope, Nuclear Pore Complexes, and Nuclear Lamina Changes During Pronuclear Development 43817.4 Molecular Mechanism of Paternal and Maternal Pronucleus Biogenesis 44017.5 Role of UPS in Pronuclear Biogenesis 44217.6 Posttranslational Modifications of Pronuclear Histones 44317.7 Sirtuin Family Histone Deacetylases in Gametogenesis and Development 44617.8 Clinical and Technological Considerations 44717.9 Conclusions 450Acknowledgments 450References 45018 Alterations of the Epigenome Induced by the Environment in Reproduction 467Zhao-Jia Ge, Shen Yin, and Heide Schatten18.1 Introduction 46718.2 Epigenetic Reprogramming 46718.3 Environment and Epigenetic Alterations 47018.4 Animal Models Used in Reproduction to Research Epigenetic Alterations Induced by the Environment 47218.5 Effects of Environment on Epigenetic Modifications in Humans 47518.6 Epigenetics and Assisted Reproductive Technology (ART) 47518.7 Priorities for the Future 476Acknowledgments 476References 47619 Toward Development of Pluripotent Porcine Stem Cells by Road Mapping Early Embryonic Development 485Stoyan Petkov, Kristine Freude, Kaveh Mashayekhi, Poul Hyttel, and Vanessa Hall19.1 Introduction 48519.2 Current Status on the Pluripotent State in the Pig Embryo 48919.3 Current Status of the Establishment of Porcine Embryonic Stem Cells (pESCs) 49119.4 Current Status in Establishment of Porcine-Induced Pluripotent Stem Cells 49419.5 Future Perspectives: Use of Global Profiling on Pluripotent Cells from Pig Embryo and Pluripotent Stem Cells 49919.6 Discussion and Conclusions 501Acknowledgments 502References 50220 Applications of Metabolomics in Reproductive Biology 509Ana Luiza Cazaux Velho, Rodrigo Oliveira, Thu Dinh, Arlindo Moura, Abdullah Kaya, and Erdogan Memili20.1 Introduction 50920.2 Metabolomics and Reproductive Biology 51020.3 Metabolomics Studies in Large Animals as Models for Humans 51320.4 Conclusions and Future Prospects 513Acknowledgments 514Conflict of Interest 514References 51421 Cryopreservation of Mammalian Oocytes 519Muhammad Anzar21.1 Principles of Cryopreservation 51921.2 Cryopreservation of Mammalian Oocytes 522Acknowledgments 542Abbreviations 543References 543Index 557