Animal Models and Human Reproduction

Our knowledge of reproductive biology has increased enormously in recent years on cellular, molecular, and genetic levels, leading to significant breakthroughs that have directly benefitted in vitro fertilization (IVF) and other assisted reproductive technologies (ART) in humans and animal systems.

Animal Models and Human Reproduction presents a comprehensive reference that reflects the latest scientific research being done in human reproductive biology utilizing domestic animal models. Chapters on canine, equine, cow, pig, frog, and mouse models of reproduction reflect frontier research in placental biology, ovarian function and fertility, non-coding RNAs in gametogenesis, oocyte and embryo metabolism, fertilization, cryopreservation, signal transduction pathways, chromatin dynamics, epigenetics, reproductive aging, and inflammation. Chapters on non-human primate models also highlight recent advancements into such issues as human in vitro fertilization (IVF) and assisted reproductive technologies (ART).

This book offers animal scientists, reproductive biology scientists, clinicians and practitioners, invaluable insights into a wide range of issues at the forefront of human reproductive health.

List of Contributors xv

1 Anatomy of the Reproductive System 1
Gheorghe M. Constantinescu

1.1 Male Genital Organs in Domestic Mammals 1

1.2 Female Genital Organs in Domestic Mammals 5

1.3 The Genital System in Domestic Mammals Species by Species 9

1.4 Genital Organs in Laboratory Mammals 35

References 56

2 Anatomy of Mammalian (Endocrine) Glands Controlling the Reproduction 59
Gheorghe M. Constantinescu

2.1 The Hypothalamus Including the Hypophysis 59

2.2 The Cerebral Epiphysis 61

2.3 The Thyroid Gland 61

2.4 The Adrenal Glands 62

2.5 The Sexual Glands 63

2.6 The Liver 63

References 63

3 Models for Investigating Placental Biology 65
Laramie Pence and Bhanu P. Telugu

3.1 Introduction 65

3.2 Classification of Placenta 66

3.3 Development of Human Placenta 69

3.4 Modeling Placental Development and Diseases of Placental Origin 73

3.5 Summary 82

References 82

4 Early Developmental Programming of the Ovarian Reserve, Ovarian Function, and Fertility 91
Francesca Mossa, Siobhàn W. Walsh, Alex C.O. Evans, Fermin Jimenez-Krassel, and James J. Ireland

4.1 Introduction 91

4.2 Impact of Prenatal Environmental Challenges on Fetal Oogonia (Germ Cells) 92

4.3 Impact of Prenatal Environmental Challenges on Fetal Follicle/Oocyte Numbers (Healthy versus Atretic) and Oocyte Quality 94

4.4 Impact of Prenatal Environmental Challenges on the Ovarian Reserve (Total Number of Morphologically Healthy Follicles/Oocytes in Ovaries) in Offspring 95

4.5 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 98

4.6 Impact of Prenatal Environmental Challenges on Fertility (as Measured by Conception Rates, Fecundity, or Age at Puberty or Menopause) in Offspring 100

4.7 Summary and Conclusion 101

References 102

5 Small Non-Coding RNAS in Gametogenesis 109
Lukasz Smorag and D. V. Krishna Pantakani

5.1 Small Non-Coding RNAs 109

5.2 Function of sncRNAs in Gametogenesis 109

Acknowledgment 119

References 119

6 The Ovarian Follicle of Cows as a Model for Human 127
Marc-André Sirard

6.1 Introduction 127

6.2 A Similar Physiology of Folliculogenesis 128

6.3 Assisted Reproduction 131

6.4 Testing the Competence Hypothesis 136

6.5 Conclusion 136

References 136

7 Production of Energy and Determination of Competence: Past Knowledge, Present Research, and Future Opportunities in Oocyte and Embryo Metabolism 145
Jason R. Herrick, Elena Silva, and Rebecca L. Krisher

7.1 Introduction 145

7.2 Measuring Metabolism 145

7.3 The Relationship Between Oocyte Metabolism and Quality 148

7.4 Embryo Metabolism 152

7.5 Metabolic Biomarkers 157

7.6 Toward Personalized Culture Media: Formulating Media for Specific Maternal Conditions 158

7.7 Summary 161

References 162

8 Signal Transduction Pathways in Oocyte Maturation 177
François J. Richard, Nicolas Santiquet, Annick Bergeron, and Daulat Raheem Khan

8.1 Introduction 177

8.2 Phosphodiesterase 181

8.3 Gap Junction Communications 192

8.4 Metabolic Switch (AMPK) 193

8.5 Conclusion 198

References 198

9 Pig Models of Reproduction 213
B.R. Mordhorst and R.S. Prather

9.1 Introduction 213

9.2 Early Embryonic Development 213

9.3 Oocyte Maturation 215

9.4 Fertilization 216

9.5 Tubouterine Contractility 216

9.6 Development to the Blastocyst Stage 216

9.7 Pregnancy and Developmental Programming 217

9.8 Puberty 222

9.9 Reproductive Disease 223

9.10 Summary 223

Acknowledgments 223

References 223

10 The Mare as an Animal Model for Reproductive Aging in the Woman 235
Elaine M. Carnevale

10.1 Introduction 235

10.2 Ovarian Activity and Reproductive Cycles 236

10.3 The Follicle 238

10.4 Fertility 239

10.5 The Oocyte 240

10.6 Conclusions 242

References 242

11 Spotlight on Reproduction in Domestic Dogs as a Model for Human Reproduction 247
Shirley J. Wright

11.1 Introduction 247

11.2 Dog Reproduction 255

11.3 Dog-Assisted Reproductive Technology 321

11.4 Dog Contraception 328

11.5 The Dog as a Model for Human Reproduction 328

11.6 Concluding Statements 332

Acknowledgments 333

References 333

12 Animal Models of Inflammation During Pregnancy 359
Karen E. Racicot and Keith E. Latham

12.1 Introduction 359

12.2 Local Inflammation of the Pregnant Female Reproductive Tract 360

12.3 Systemic Inflammation During Pregnancy 361

12.4 Genetic Models and Cellular Manipulation to Study Inflammation During Pregnancy 365

12.5 Inflammation During Pregnancy and Offspring Disease 370

12.6 Perspectives and Conclusions 372

Acknowledgments 373

References 373

13 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 383
Ken-ichi Sato

13.1 Introduction to Reproductive Biology of Frog Oocytes and Eggs 383

13.2 Practical Approaches 383

13.3 Achievements and Perspectives 395

Acknowledgments 396

Appendix 396

References 399

14 Prezygotic Chromosomal Examination of Mouse Spermatozoa 401
Hiroyuki Watanabe and Hiroyuki Tateno

14.1 Introduction 401

14.2 Procedure of Sperm Chromosome Screening 402

14.3 Practical Use of SCS Before Fertilization 404

14.4 Conclusion 406

Acknowledgments 406

Addendum 406

References 406

15 Molecular and Cellular Aspects of Mammalian Sperm Acrosomal Exocytosis 409
Florenza A. La Spina, Cintia Stival, Dario Krapf, and Mariano G. Buffone

15.1 Introduction 409

15.2 Structure of the Acrosome 409

15.3 Intermediate Stages of Exocytosis 412

15.4 Sperm Capacitation Prepare the Sperm to Undergo Acrosomal Exocytosis 412

15.5 Physiological Site for the Occurrence of Acrosomal Exocytosis 414

15.6 SNARES and Other Proteins from the Fusion Machinery 416

15.7 Hyperpolarization 417

15.8 Actin Cytoskeleton 417

15.9 Calcium 418

References 419

16 Sperm Chromatin Dynamics Associated with Male Fertility in Mammals 427
Naseer A. Kutchy, Sule Dogan, Abdullah Kaya, Arlindo Moura, and Erdogan Memili

16.1 Introduction 427

16.2 Sperm Chromatin Structure Modulates Sperm Nuclear Shape and Function 429

16.3 The Bull Is a Suitable Model for the Study of Male Fertility in Humans 430

16.4 Conclusions and Prospects 430

Acknowledgments 431

References 431

17 Epigenome Modification and Ubiquitin-Dependent Proteolysis During Pronuclear Development of the Mammalian Zygote: Animal Models to Study Pronuclear Development 435
Jan Nevoral and Peter Sutovsky

17.1 Introduction 435

17.2 Milestones of Pronuclear Development 436

17.3 Nuclear Envelope, Nuclear Pore Complexes, and Nuclear Lamina Changes During Pronuclear Development 438

17.4 Molecular Mechanism of Paternal and Maternal Pronucleus Biogenesis 440

17.5 Role of UPS in Pronuclear Biogenesis 442

17.6 Posttranslational Modifications of Pronuclear Histones 443

17.7 Sirtuin Family Histone Deacetylases in Gametogenesis and Development 446

17.8 Clinical and Technological Considerations 447

17.9 Conclusions 450

Acknowledgments 450

References 450

18 Alterations of the Epigenome Induced by the Environment in Reproduction 467
Zhao-Jia Ge, Shen Yin, and Heide Schatten

18.1 Introduction 467

18.2 Epigenetic Reprogramming 467

18.3 Environment and Epigenetic Alterations 470

18.4 Animal Models Used in Reproduction to Research Epigenetic Alterations Induced by the Environment 472

18.5 Effects of Environment on Epigenetic Modifications in Humans 475

18.6 Epigenetics and Assisted Reproductive Technology (ART) 475

18.7 Priorities for the Future 476

Acknowledgments 476

References 476

19 Toward Development of Pluripotent Porcine Stem Cells by Road Mapping Early Embryonic Development 485
Stoyan Petkov, Kristine Freude, Kaveh Mashayekhi, Poul Hyttel, and Vanessa Hall

19.1 Introduction 485

19.2 Current Status on the Pluripotent State in the Pig Embryo 489

19.3 Current Status of the Establishment of Porcine Embryonic Stem Cells (pESCs) 491

19.4 Current Status in Establishment of Porcine-Induced Pluripotent Stem Cells 494

19.5 Future Perspectives: Use of Global Profiling on Pluripotent Cells from Pig Embryo and Pluripotent Stem Cells 499

19.6 Discussion and Conclusions 501

Acknowledgments 502

References 502

20 Applications of Metabolomics in Reproductive Biology 509
Ana Luiza Cazaux Velho, Rodrigo Oliveira, Thu Dinh, Arlindo Moura, Abdullah Kaya, and Erdogan Memili

20.1 Introduction 509

20.2 Metabolomics and Reproductive Biology 510

20.3 Metabolomics Studies in Large Animals as Models for Humans 513

20.4 Conclusions and Future Prospects 513

Acknowledgments 514

Conflict of Interest 514

References 514

21 Cryopreservation of Mammalian Oocytes 519
Muhammad Anzar

21.1 Principles of Cryopreservation 519

21.2 Cryopreservation of Mammalian Oocytes 522

Acknowledgments 542

Abbreviations 543

References 543

Index 557

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