Oxidants, Antioxidants, and Impact of the Oxidative Status in Male Reproduction

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Oxidants, Antioxidants, and Impact of the Oxidative Status in Male Reproduction
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Contributors
Foreword
Preface
Introduction
	REFERENCES
Part I: Basic Aspects
1.1. Life Under Aerobic Conditions
	INTRODUCTION
	THE GREAT OXYGENATION EVENT
	BIOLOGICAL LIFE AND ENVIRONMENTAL EVOLUTION
	AEROBIC RESPIRATION AND THE MITOCHONDRIA
	REDOX BIOLOGY AND THE PARADOXICAL NATURE OF AEROBIC LIFE
	ENDOGENOUS ANTIOXIDANTS AND OXIDATIVE STRESS
	MITOCHONDRIAL DYSFUNCTION
	CONCLUSION
	GLOSSARY
	LIST OF ACRONYMS AND ABBREVIATIONS
	REFERENCES
1.2. The Oxidant Paradox
	Introduction
	Reactive Oxygen Species and Fertility
		Capacitation
		Sperm Maturation
	Oxidative Stress
		Cancer
		Neurodegenerative Disease
		Reperfusion Injury in Cardiovascular Disease
	Diabetes
		Outline placeholder
			Definition of Antioxidant
			Antioxidant Paradox
			Theories
			Conclusions
	References
1.3. From Past to Present: An Historical Overview of the Concept of Spermatozoa, Reactive Oxygen Species, and Male-Factor Infert ...
	Definition of Reactive Oxygen Species
	The Foundation of the Theory of Reactive Oxygen Species in Human Sperm Ejaculates
		Spermatozoa and Their Susceptibility Toward Reactive Oxygen Species
		Sperm and Their High Amount of Polyunsaturated Fatty Acids
		Leukocytes and Their Contribution Toward Reactive Oxygen Species and Male-Factor Infertility
	What Kind of Oxidase Are We Dealing With?
		What About Other Sources of Reactive Oxygen Species in Sperm?
		The Potential for NOX5-Involvement in a NADPH-ROS Generating System
		The Involvement of Mitochondria in Reactive Oxygen Species and Spermatozoa
	Other Measurements of Reactive Oxygen Species: The Challenge in Moving the Field Forward and Why We Cannot Continue to Do a ...
		Luminol/Horseradish Peroxidase
		Dihydroethidium
		DNA Oxidation and Its Measurement of Reactive Oxygen Species
	Conclusion
	References
1.4. Basic Aspects of Oxidative Stress in Male Reproductive Health
	Introduction
	Pathological Effects of Oxidative Stress on Spermatozoa and Their Functional Capacity
		Lipid Peroxidation
		Apoptosis
		Sperm Motility
		Sperm DNA Damage
	Difference in Oxidative Stress Between Fertile and Infertile Men
	Role of Oxidative Stress Assays in Unexplained Male Infertility
	Selection of Non-DNA Damaged Sperm
	Reversal of Oxidative Stress
	Conclusion
	References
1.5. Leukocytes as a Cause of Oxidative Stress
	ORIGIN AND FUNCTION OF SEMINAL LEUKOCYTES
	SECRETIONS OF LEUKOCYTES
	NATURE AND FEATURES OF REACTIVE OXYGEN SPECIES
	OXIDATIVE STRESS
	EFFECT OF OXIDATIVE STRESS ON SPERM FUNCTIONS AND MALE FERTILITY
		Oxidative Damage to Membrane Lipids
		Oxidative Damage to DNA
	CONCLUSION
	REFERENCES
1.6. Human Spermatozoa and Interactions With Oxidative Stress
	INTRODUCTION
	WHAT ARE REACTIVE OXYGEN SPECIES?
	PHYSIOLOGICAL ROLES OF REACTIVE OXYGEN SPECIES IN SEMINAL PLASMA
	REACTIVE OXYGEN SPECIES GENERATION IN SPERMATOZOA
	MECHANISM OF REACTIVE OXYGEN SPECIES PRODUCTION BY SPERMATOZOA
	NADPH OXIDASES GENERATED REACTIVE OXYGEN SPECIES BY SPERMATOZOA: ROLE IN CAPACITATION
	NITRIC OXIDE SYNTHASE GENERATED REACTIVE NITROGEN SPECIES BY SPERMATOZOA DURING CAPACITATION
	REACTIVE OXYGEN SPECIES AND IMMATURE SPERMATOZOA
	APOPTOSIS AND THE ROLE OF REACTIVE OXYGEN SPECIES GENERATION
	ANTIOXIDANT EXPRESSION IN SPERMATOZOA
	CONCLUSION
	REFERENCES
1.7. Causes of Reductive Stress in Male Reproduction
	INTRODUCTION
	REACTIVE OXYGEN SPECIES AND THE MALE REPRODUCTIVE SYSTEM
	THE ANTIOXIDANT PARADOX
	REDUCING AGENTS IN MALE REPRODUCTION
		Reducing Agents in the Testicle and Epididymis
		Reducing Agents in Sperm Cells
		Reducing Agents in Seminal Plasma
	REDUCTIVE STRESS AND THE MALE REPRODUCTIVE SYSTEM
	CONCLUSION
	LIST OF ACRONYMS AND ABBREVIATIONS
	REFERENCES
1.8. Physiological Role of Reactive Oxygen Species in Male Reproduction
	INTRODUCTION
	REACTIVE OXYGEN SPECIES: ENDOGENOUS GENERATION AND SOURCES
	REACTIVE NITROGEN SPECIES: ENDOGENOUS GENERATION AND SOURCES
	PHYSIOLOGICAL LEVELS OF REACTIVE OXYGEN SPECIES AND SPERM FUNCTION
		Spermatogenesis and Sperm Maturation
		Capacitation, Hyperactivation, and Chemotaxis
		Acrosome Reaction
		Sperm-Oocyte Fusion
	CONCLUSION
	LIST OF ACRONYMS AND ABBREVIATIONS
	REFERENCES
Part II: Clinical Aspects
2.1. Epidemiology of Oxidative Stress in Male Fertility
	INTRODUCTION
	IDIOPATHIC
	IATROGENIC
		Centrifugation
		Cryopreservation
		Medications
	LIFESTYLE
		Advanced Paternal Age
		Dietary Antioxidant Intake
		Smoking
		Alcohol
		Obesity
		Psychological Stress
	ENVIRONMENTAL
		Air Pollution
		Pesticides
		Plasticizers
		Heavy Metals
		Non-ionizing Radiation
	INFECTION
		Genitourinary Tract
		Systemic
	AUTOIMMUNE
		Vasectomy Reversal
		Chronic Nonbacterial Prostatitis
	TESTICULAR
		Varicocele
		Testicular Torsion
		Cryptorchidism
	CHRONIC DISEASE
		Diabetes
		Chronic Kidney Disease
		β-thalassemia
		Thyroid Dysfunction
		Hyperhomocysteinemia
	CONCLUSION
	LIST OF ACRONYMS AND ABBREVIATIONS
	REFERENCES
2.2. Role of Oxidative Stress in the Etiology of Male Infertility and the Potential Therapeutic Value of Antioxidants
	INTRODUCTION
	SUMMARY OF CURRENT UNDERSTANDING IN RELATION TO HUMAN SPERMATOZOA
	OXIDATIVE STRESS AND ITS IMPACT ON SPERM CELL STRUCTURES AND FUNCTIONS
		Sperm-Zona Recognition
		Sperm-Oocyte Fusion
	SPERM NUCLEAR OXIDATIVE STRESS AND ITS DEVELOPMENTAL IMPACT
		Sperm Nuclear and DNA Damage
		Oxidative Alterations of the Sperm Nucleus and Epigenetic Information
	THERAPEUTIC VALUE OF ANTIOXIDANT TREATMENTS
		What Are Antioxidants?
		Why Antioxidants?
		Designing Antioxidant Therapeutics
	REFERENCES
2.3. Male Genital Tract Infections and Leukocytospermia
	DEFINITION
	ETIOLOGY AND PHYSIOPATHOLOGY
	CLINICAL AND LABORATORY FINDINGS
	TREATMENT
	CONCLUSIONS
	REFERENCES
	FURTHER READING
2.4. Varicocele
	INTRODUCTION
	ANATOMY
	DIAGNOSIS
		Ultrasound
		Other Diagnostic Modalities
	VARICOCELES AND MALE INFERTILITY
		Semen Characteristics
		Pathophysiology
	MECHANISMS OF REACTIVE OXYGEN SPECIES PRODUCTION
		Scrotal Hyperthermia
		Renal and Adrenal Metabolites
		Hypoperfusion and Hypoxia
	MOLECULAR MECHANISMS
		Nitric Oxide Production
		Reactive Oxygen Species Production by Mitochondria
		Heat Shock Proteins
		Heme Oxygenase
		Xanthine Oxidase
		Epididymal Damage
	TREATMENT OF VARICOCELE-RELATED OXIDATIVE STRESS
		Measurement of Oxidative Stress
		Varicocele Repair
		Semen Analysis and Pregnancy Outcomes
		Treatment With Antioxidants
	CONCLUSIONS
	REFERENCES
2.5. Malnutrition and Obesity
	INTRODUCTION
	KEY NUTRIENTS ASSOCIATED WITH MALE REPRODUCTION AND INFERTILITY
	HUMAN ADIPOSE TISSUE
	UNDERNUTRITION AND UNDERWEIGHT MALES
	OBESITY: CLINICAL DEFINITION, RISK FACTORS, AND EPIDEMIOLOGY
	CLINICAL ASSESSMENT OF ADIPOSITY AND FAT DISTRIBUTION
	PATHOPHYSIOLOGICAL DERANGEMENTS OF OBESITY: THE METABOLIC SYNDROME
	OBESITY, METABOLIC SYNDROME, AND MALE REPRODUCTION OUTCOMES
	OBESITY AND MICRONUTRIENT DEFICIENCIES
	OBESITY, OXIDATIVE STRESS, AND THE MALE REPRODUCTIVE SYSTEM
	NUTRITION, WEIGHT MANAGEMENT PROGRAMS, AND MALE REPRODUCTIVE OUTCOMES
	NUTRITIONAL SUPPLEMENTATION AND ANTIOXIDANTS
	CONCLUSION
	GLOSSARY
	LIST OF ACRONYMS AND ABBREVIATIONS
	REFERENCES
2.6. Role of Reactive Oxygen Species in Diabetes-Induced Male Reproductive Dysfunction
	INTRODUCTION
	CURRENT KNOWLEDGE ON THE EFFECTS OF DIABETES MELLITUS IN MALE FERTILITY
	DIABETES MELLITUS, OXIDATIVE STRESS, AND TESTICULAR METABOLISM
	IMPACT OF REACTIVE OXYGEN SPECIES ON MALE FERTILITY: FROM SPERMATOGENESIS TO SPERM MATURATION
	POSSIBLE ROLE OF ANTIOXIDANTS IN THE TREATMENT OF DIABETES-INDUCED MALE INFERTILITY
	CONCLUSION
	LIST OF ACRONYMS AND ABBREVIATIONS
	ACKNOWLEDGMENTS
	REFERENCES
2.7. Thyroid Dysfunction and Testicular Redox Status: An Intriguing Association
	INTRODUCTION
	THYROID HORMONE AND ITS MODE OF ACTION
	THYROID HORMONE AND TESTES
		Role of Thyroid Hormone in Testicular Development
		Impact of Altered Postnatal Thyroid Hormone Status on Adult Testes
		Thyroid Receptors in Testicular Cells
		Expression of Thyroid Hormone Transporter and Manifestation of Iodothyronine Deiodinase
	THYROID DYSFUNCTION AND OXIDATIVE STRESS IN TESTES
		Hypothyroidism
		Hyperthyroidism
	THYROID DYSFUNCTION AND ANTIOXIDANT DEFENSES IN TESTES
		Hypothyroidism
		Hyperthyroidism
	THYROID DYSFUNCTION, MALE INFERTILITY, ANTIOXIDANT TREATMENT, AND TESTICULAR FUNCTION
	THYROID DYSFUNCTION AND ASSISTED REPRODUCTIVE TECHNOLOGY OUTCOME
	CONCLUSION
	LIST OF ABBREVIATIONS
	REFERENCES
2.8. Aging
	INTRODUCTION
	MITOCHONDRIAL FREE RADICAL THEORY OF AGING
	SPERM DNA DAMAGE/FRAGMENTATION, REACTIVE OXYGEN SPECIES, AND AGING
		Effects of Reactive Oxygen Species and Advanced Paternal Age on Health of Offspring
	ANTIOXIDANTS
	APOPTOSIS
	REACTIVE OXYGEN SPECIES, AGING, AND TELOMERE LENGTH
	CONCLUSION
	GLOSSARY
	LIST OF ACRONYMS AND ABBREVIATIONS
	REFERENCES
Part III: Clinical Methods to Determine and Treat Oxidative Stress
3.1. Reactive Oxygen Species Methodology Using Chemiluminescence Assay
	INTRODUCTION
	METHODS FOR MEASURING REACTIVE OXYGEN SPECIES
	MEASUREMENT OF REACTIVE OXYGEN SPECIES BY CHEMILUMINESCENCE
		Principle
	TYPES OF LUMINOMETERS
		Single or Double Tube Luminometer
		Multitube Luminometer
		Microplate Luminometer
			Measurement of Reactive Oxygen Species in Semen by AutoLumat Luminometer
	INSTRUMENT AND CONSUMABLES
		Reagents
		Semen Analysis
		Sample Preparation for Reactive Oxygen Species
		Instrument Setup
		Measurement of Reactive Oxygen Species
		Calculation and Result Interpretation
		Reference Values of Reactive Oxygen Species
	ASSAY QUALITY CONTROL
	ADVANTAGES AND DISADVANTAGES OF MEASURING REACTIVE OXYGEN SPECIES BY CHEMILUMINESCENCE
		Advantages
		Disadvantages
	LIMITATIONS OF ASSAY
	FACTORS AFFECTING CHEMILUMINESCENT SIGNALS
	NEWER TECHNIQUE TO MEASURE OXIDATIVE STRESS
	CONCLUSION
	REFERENCES
3.2. NBT Test
	INTRODUCTION: FREE RADICALS: TWO-EDGED MOLECULES IN MALE REPRODUCTION
		Superoxide: The Backbone of Cellular Oxidative Balance
	CURRENT METHODS FOR SUPEROXIDE DETECTION IN SEMEN
	THE NITROBLUE TETRAZOLIUM TEST: A COLORIMETRIC MARKER OF SUPEROXIDE IN SEMEN
	CLINICAL AND EXPERIMENTAL DATA: PRINCIPLES AND INTERPRETATIONS
	EXISTING ISSUES
		Chemistry of the Nitroblue Tetrazolium Reduction
		Leukocytospermia
		Concentration of Spermatozoa
		Lack of Clinical Data
	CONCLUSION: CLINICAL IMPACT AND FUTURE STATUS OF THE NITROBLUE TETRAZOLIUM TEST
	ACKNOWLEDGMENTS
	REFERENCES
3.3. Total Antioxidant Capacity Measurement by Colorimetric Assay
	INTRODUCTION
	METHODS FOR MEASURING ANTIOXIDANTS
	TYPES OF ASSAYS FOR TOTAL ANTIOXIDANT MEASUREMENT
		Chemiluminescence Assays (ECL Assays)
		Spectrophotometric Assay: Ferric Reducing of Antioxidant Power Assay
		Assay-based on Formation of ABTS Radical: ELISA Assay
	MEASUREMENT OF ANTIOXIDANT CAPACITY BY COLORIMETRIC ASSAY
		Instrument and Consumables
		Assay Reagents
		Methodology
			Specimen Collection
		Instrument Setup
		Principle of the Assay
		Reagent Preparation for Total Antioxidant Capacity
			Sample Preparation for Total Antioxidant Capacity
		Calculating Assay Results
		Reference Values and Ranges
		Assay Quality Control
		Tips for Troubleshooting
	CONCLUSIONS
	REFERENCES
	3.3. . APPENDIX A
3.4. Oxidation-Reduction Potential Methodology Using the MiOXSYS System
	INTRODUCTION
	CLINICAL SIGNIFICANCE OF OXIDATION-REDUCTION POTENTIAL
	METHODS FOR MEASURING OXIDATIVE STRESS
	OXIDATION-REDUCTION POTENTIAL MEASUREMENT: REVIEW OF THE CURRENT TECHNOLOGY
	MEASUREMENT OF OXIDATION-REDUCTION POTENTIAL BY THE MIOXSYS SYSTEM
		Principle
	INSTRUMENTS AND CONSUMABLES
		Semen Collection and Preparation
		Instrument Setup
		Analyzing the Sample
		Calculation and Result Interpretation
		Reference Values of Oxidation-Reduction Potential
	ASSAY QUALITY CONTROL
	ADVANTAGES AND DISADVANTAGES OF OXIDATION-REDUCTION POTENTIAL MEASUREMENT BY MIOXSYS
	FACTORS AFFECTING MEASUREMENT
	MANAGEMENT OF ABNORMAL OXIDATION-REDUCTION POTENTIAL
	CONCLUSION
	REFERENCES
3.5. Treatment of Sperm Oxidative Stress: A Collaborative Approach Between Clinician and Embryologist
	INTRODUCTION
	CLINICAL CAUSES OF OXIDATIVE STRESS AND THEIR TREATMENT
		Toxins
		Ejaculatory Frequency
		Stress
		Temperature
		Infection/Inflammatory
		Cancer
		Unhealthy Lifestyle
		Anatomical
		Radiation
	ANTIOXIDANT SUPPLEMENTS TO AUGMENT SPERM QUALITY
	LABORATORY PROCEDURES TO MINIMIZE OXIDATIVE DAMAGE TO SPERM DURING ASSISTED REPRODUCTIVE TECHNIQUE TREATMENT
	CONCLUDING REMARKS
	LIST OF ACRONYMS AND ABBREVIATIONS
	REFERENCES
Part IV: Current Approaches: The OMICS
4.1. Genomics and Epigenetics
	INTRODUCTION
	EPIGENETICS
		Deoxyribonucleic Acid Methylation
		Histones
		Non-DNA Methylation
		Acetylation of Histones
		Phosphorylation
		Ubiquitylation and Sumoylation
	EPIGENETICS IN MALE REPRODUCTION
		Drugs
		Diet
		Environment
	OXIDATIVE STRESS
	REACTIVE OXIDATIVE SPECIES AND EPIGENETICS
		Protamine Transition
		DNA Fragmentation
		Other Mechanisms
	FINAL THOUGHTS
	REFERENCES
4.2. Transcriptomics and Oxidative Stress in Male Infertility
	INTRODUCTION
	METHODS USED IN TRANSCRIPTOMIC ANALYSES
		Microarray Technique
		RNA Sequencing
	TRANSCRIPTOMICS AND MALE INFERTILITY
	TRANSCRIPTOMIC STUDIES ON MALE INFERTILITY AND OXIDATIVE STRESS
	CONCLUSIONS
	GLOSSARY
	LIST OF ACRONYMS AND ABBREVIATIONS
	REFERENCES
	FURTHER READING
4.3. Oxidative Stress and Sperm Dysfunction: An Insight Into Dynamics of Semen Proteome
	INTRODUCTION
	PROTEOMICS: THE TOOLS
	REACTIVE OXYGEN SPECIES AND SEMEN PROTEOME
	SPERM PROTEOME IN PATHOPHYSIOLOGICAL CONDITION WITH OXIDATIVE PREDOMINANCE
		Varicocele
		Asthenozoospermia
		Oligozoospermia and Idiopathic Oligoasthenoteratozoospermia
		Leukocytospermia
		Unexplained Infertility
		Sperm Proteome and Assisted Reproductive Technique Outcome
	REACTIVE OXYGEN SPECIES-MEDIATED POSTTRANSLATIONAL PROTEIN MODIFICATIONS AND MALE REPRODUCTION
		Phosphorylation
		Thionylation
		S-Nitrosylation
		Carbonylation
	UBIQUITINATION AND PROTEOLYSIS
	CONCLUDING REMARKS
	REFERENCES
4.4. Metabolomics
	The Current Situation of Male Fertility
	Assisted Reproduction Techniques, Their Outcomes and Limitations
	The Relevance of Male Factor in Reproductive Results
	How to Estimate Male Fertility Potential, Its Limitations, and Potentially Useful Techniques to Be Applied
	Exploring Male Fertility Biomarkers Through the Omics
	Metabolomics in Male Fertility Studies
	Conclusions
	References
Index
	A
	B
	C
	D
	E
	F
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	H
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	N
	O
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	Q
	R
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	U
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	W
	X
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