Biologic Markers in Reproductive Toxicology -- Copyright -- Preface -- Contents -- Executive Summary -- ORGANIZATION OF THIS REPORT -- CONCEPTS AND DEFINITIONS -- Markers of Exposure -- Markers of Effect -- Markers of Susceptibility -- EXTRAPOLATION FROM ANIMALS TO HUMANS -- QUALITY AND QUANTITY OF DATA -- BIOLOGIC MARKERS ASSOCIATED WITH REPRODUCTIVE AND NEURODEVELOPMENTAL TOXICOLOGY -- BIOLOGIC MARKERS ASSOCIATED WITH MALE REPRODUCTION -- Markers of Physiologic Damage -- Markers of Genetic Damage and Heritable Mutations -- BIOLOGIC MARKERS ASSOCIATED WITH FEMALE REPRODUCTION -- Germ Cell Damage -- Development and Aging -- Cyclic Ovarian Function -- Fertilization, Implantation, and Early Loss -- BIOLOGIC MARKERS ASSOCIATED WITH PREGNANCY -- BIOLOGIC MARKERS ASSOCIATED WITH NEURODEVELOPMENT -- GENERAL RECOMMENDATIONS AND CONCLUSIONS -- 1 Report of the Oversight Committee -- CONCEPTS AND DEFINITIONS -- Biologic Markers of Exposure -- Biologic Markers of Effect -- Biologic Markers of Susceptibility -- PRINCIPLES OF SELECTION OF MARKERS -- Biologic Considerations -- Practical Limitations -- Batteries of Biologic Markers -- Ethical Issues -- VALIDATION OF BIOLOGIC MARKERS -- Sensitivity and Specificity -- Uses -- Animal Models -- Quality Assurance -- Sensitivity of Measurements -- Markers of Specific Exposures -- ECOLOGIC MARKERS -- USE OF BIOLOGIC MARKERS IN RISK ASSESSMENT -- EXTRAPOLATION FROM ANIMALS TO HUMANS -- QUALITY AND QUANTITY OF DATA -- IMPLEMENTATION OF BIOLOGIC MARKERS IN POPULATION STUDIES -- LONG-TERM TISSUE AND CELL STORAGE FOR RETROSPECTIVE ANALYSIS -- USE OF BIOLOGIC MARKERS IN REPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY -- Studies of Male Reproductive Toxicants -- Studies of Female Reproductive Toxicants -- Studies of Pregnancy Toxicants -- Studies of Neurodevelopmental Toxicants -- SUMMARY.

I Biologic Markers in Male Reproductive and Gametic Genetic Toxicology -- 2 Introduction -- BIOLOGIC MARKERS OF MALE PHYSIOLOGIC DAMAGE -- BIOLOGIC MARKERS OF GENETIC DAMAGE AND HERITABLE MUTATIONS IN HUMAN GERM CELLS -- IMPORTANCE OF ANIMAL STUDIES IN MARKER DEVELOPMENT -- ORGANIZATION OF MALE REPRODUCTION SECTION -- 3 Clinical Evaluation of Male Infertility -- MEDICAL HISTORY -- PHYSICAL EXAMINATION -- SEMEN CHARACTERISTICS -- 4 Biologic Markers of Testicular Function -- PHYSICAL AND CHEMICAL MARKERS OF TESTICULAR FUNCTION -- Markers in Use -- Markers Requiring Research and Development -- LEYDIG CELLS -- Markers in Use -- Markers Requiring Research and Development -- SEMINIFEROUS TUBULES -- Sertoli Cells -- Markers in Use -- Markers Requiring Research and Development -- Germ Cells -- Markers in Use -- Markers Requiring Research and Development -- 5 Biologic Markers of Epididymal Structure and Function -- MARKERS OF EPIDIDYMAL TISSUE -- CHANGES IN MATURING SPERMATOZOA -- Structural Changes -- Biochemical Changes -- Functional Changes -- Content of Epididymal Spermatozoa -- Transport of Spermatozoa -- Acquisition of Fertilizing Ability -- Storage of Spermatozoa -- EPIDIDYMAL LUMINAL FLUID -- EPIDIDYMAL EPITHELIAL FUNCTION -- Histology -- Presence and Relative Distribution of Various Cell Types -- Blood-Epididymis Barrier -- Spermiophagy -- Biochemical Markers -- Hormone Receptors and Regulation of Epididymal Function -- Steroid Biosynthesis and Metabolism -- Intermediary Metabolism -- EPIDIDYMALLY MEDIATED TOXIC DRUG EFFECTS -- 6 Biologic Markers of Accessory Sex Organ Structure and Function -- PHYSICAL MARKERS -- STRUCTURAL MARKERS -- FUNCTIONAL MARKERS -- 7 Biologic Markers of Human Male Reproductive Health and Physiologic Damage -- NEEDS FOR BIOLOGIC MARKERS OF HUMAN MALE REPRODUCTIVE HEALTH.

EPIDEMIOLOGIC STUDIES OF HUMAN SPERM PRODUCTION AND FERTILITY -- Epidemiologic Surveys of Fertility Status -- Markers of Early Pregnancy -- Cohort Studies with Semen and Blood Samples -- HUMAN SPERMATOGENESIS AND DEVELOPMENT OF SEMEN-BASED MARKERS OF MALE REPRODUCTIVE HEALTH -- PHYSICAL CHARACTERISTICS OF THE HUMAN EJACULATE -- PRESENCE OF NONSPERM CELLS IN SEMEN -- SPERM NUMBER -- As Marker of Sperm Production -- As Marker of Fertility Status -- As Indicator of Exposure to Toxic Agents -- Other Factors That Affect Sperm Number -- SPERM STRUCTURE -- As Marker of the Quality of Sperm Production -- As Marker of Fertility Status -- As Indicator of Exposure to Toxic Agents -- Other Factors That Affect Sperm Structure -- SPERM MOTILITY -- As Marker of Sperm Function -- As Marker of Fertility Status -- As Indicator of Exposure to Toxic Agents -- Other Factors That Affect Sperm Motility -- SPERM VIABILITY -- SPERM FUNCTION -- Cervical-Mucus Penetration -- Sperm-Oocyte Interaction -- OTHER SPERM MEASUREMENTS -- Sperm Agglutination -- Nuclear Chromatin -- Double F Bodies -- CHEMICAL COMPOSITION OF SEMINAL FLUID -- PROMISING RESEARCH CONCEPTS -- Automated Sperm Measurements -- Machine-Based Sperm-Motility Measurements -- Quantitative Sperm Structure -- General Considerations Regarding Automated Methods -- Markers of Sperm Function -- Immunologic Reagents for Studies of Semen and Spermatogenesis -- Sperm Surface Domains -- Components in the Sperm -- Use of Antibodies for Studying Gene Expression -- Antibodies for Characterizing Semen -- SEMEN MARKERS OF SERTOLI CELL AND LEYDIG CELL FUNCTION -- RECOMBINANT-DNA METHODS FOR STUDY OF HUMAN SPERMATOGENESIS AND SEMEN -- 8 Assessing Transmitted Mutations in Mice -- ASSESSING MARKERS IN LABORATORY ANIMALS -- MARKERS OF EXPOSURE -- Cytotoxicity -- Cytogenetic Effects -- Biochemical Responses -- Molecular Binding.

Cellular Morphologic Responses -- TESTS IN MICE TO DETERMINE TRANSMITTED GENETIC EFFECTS -- Specific-Locus Test with Visible Markers -- Specific-Locus Test with Biochemical Markers -- Specific-Locus Test with Immunologic Markers (H Test) -- Recessive Lethal Test -- Dominant Lethal Test -- Heritable-Translocation Test -- Inversions -- Sex-Chromosome Loss -- Nondisjunction Test -- Cytogenetic Analysis of Zygotes -- Tests for Dominant Mutations -- NEEDED RESEARCH ON GENETIC DAMAGE IN LABORATORY ANIMALS -- Relationship Between Molecular Target Sites and Production of Various Types of Mutations -- Molecular Nature and Expression of Mutations -- Mutagen-Caused Induction of Integration of Endogenous Transposable Elements in New Sites -- Mouse Mutants as Models of Human Genetic Diseases -- Nondisjunction -- DNA Methods -- 9 Markers for Measuring Germinal Genetic Toxicity and Heritable Mutations in People -- CURRENT METHODS FOR MEASURING HUMAN HERITABLE MUTATIONS -- Sentinel Phenotypes -- Chromosomal Abnormalities -- Prevalence of Chromosomal Abnormalities at Birth -- Mutant Proteins -- RESULTS OF EPIDEMIOLOGIC STUDIES OF HUMAN HERITABLE MUTATIONS IN EXPOSED POPULATIONS -- Atomic Bomb Survivors -- Survivors of Cancer Chemotherapy -- Other Exposure Groups -- HUMAN SOMATIC MUTATION METHODS -- Detection of Somatic Mutations in White Blood Cells -- Detection of Somatic Mutations in Red Blood Cells -- NEW MOLECULAR APPROACHES FOR DETECTING HUMAN HERITABLE MUTATIONS -- DNA Sequencing -- Restriction-Fragment-Length Polymorphism (RFLP) -- Ribonuclease Cleavage -- Subtractive Hybridization -- Pulse-Field Gel Electrophoresis -- One-Dimensional Denaturing Gel Electrophoresis -- Two-Dimensional Denaturing Gradient Gel Electrophoresis -- TESTICULAR MARKERS OF HUMAN GERMINAL CYTOGENETIC DAMAGE -- SEMEN MARKERS OF HUMAN GERMINAL MUTATIONS AND GENETIC TOXICITY.

Cytogenetics of Human Sperm -- Sperm-DNA Alkaline Elution -- Specific-Locus Mutations in Sperm -- DNA Adduction in Sperm -- Aneuploidy Detection in Sperm -- Cytogenetic Analysis of Meiotic Cells in Semen -- Micronuclei in Seminal Spermatids -- SUMMARY -- 10 Conclusions and Recommendations -- IDENTIFICATION OF MARKERS OF ABNORMAL PHYSIOLOGIC FUNCTION -- Testes -- Epididymis -- Accessory Sex Organs -- SEMEN MARKERS OF ABNORMAL PHYSIOLOGIC FUNCTION -- NEED FOR IMPROVED MEASURES OF FERTILITY STATUS AND EXPOSURE -- IDENTIFICATION OF MARKERS OF GERMINAL GENETIC TOXICITY AND HERITABLE MUTATIONS -- CRITERIA FOR DEVELOPMENT AND VALIDATION OF MARKERS OF MALE REPRODUCTION -- STRATEGY FOR TESTING EFFECT OF TOXIC CHEMICALS ON MARKERS OF MALE REPRODUCTION -- II Biologic Markers in Female Reproductive Toxicology -- 11 Introduction -- OOGENESIS -- DEVELOPMENT OF THE FEMALE REPRODUCTIVE TRACT -- MATURATION -- Hormonal Changes -- Menarche -- Adrenarche -- Thelarche -- CYCLIC OVARIAN FUNCTION -- FERTILIZATION -- REPRODUCTIVE SENESCENCE -- 12 Biologic Markers of Genetic Damage in Females -- MARKERS OF EXPOSURE -- MARKERS OF OOCYTE TOXICITY -- MARKERS OF GENOTOXIC DAMAGE OR REPAIR -- DNA Adducts -- Unscheduled DNA Synthesis -- Sister-Chromatid Exchange -- MARKERS OF MUTATIONAL EVENTS -- Laboratory Animals -- Human Oocytes -- Human Somatic Cells -- Chromosomal Aberrations -- Micronuclei -- Specific-Locus Mutations -- 13 Biologic Markers of Reproductive Development and Aging -- MARKERS OF MATURATION -- Adrenarche -- Ovary and Uterus -- Menarche -- Thelarche and Pubic Hair -- MENSTRUATION -- LOSS OF FERTILITY AND FECUNDITY -- PRECOCIOUS MENOPAUSE -- OVARIAN OOCYTE DEPLETION -- HORMONES -- Gonadotropins -- Steroids -- NERVOUS SYSTEM -- Behavior -- Cell Populations -- OBSERVATIONS ON THE USE OF THESE MARKERS -- Need for Multiple Biologic Markers.

Differential Susceptibility of Individuals and Populations.