Front Cover

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

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

Copyright

Contents

Contributors

Foreword

Preface

Introduction

REFERENCES

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

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 ...

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

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

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

3.4 - 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

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

G

H

I

J

K

L

M

N

O

P

Q

R

S

T

U

V

W

X

Z