Male-Mediated Developmental Toxicity: (Reproductive Biology)

The cause of many of the adverse reproductive outcomes and developmental diseases among offspring is not well understood. Most of the epidemiologic and experimental animal research has focused on the relationship between maternal exposures including medications, tobacco smoke, alcohol, infections, and occupation and the occurrence of spontaneous abortion, low birth weight, and birth defects. The potential role of paternal exposures has not been investigated as extensively despite long-standing animal research that demonstrates the induction of mutations in the male germ cell after exposure to certain agents and subsequent reproductive failure or early pregnancy loss. Given this relative lack of interest, acquisition of epidemiologic data and the development of a definitive model or mechanism for potential male-mediated effects has been hindered. However, recent laboratory and epidemiologic investigations have suggested that paternal exposures may be more important than previously suspected. This topic has been termed by some as "male-mediated developmental toxicity. " This is meant to refer to the effects of exposures and other factors relating to the male parent that result in toxicity to the conceptus and abnormal development. The developmental endpoints of interest can include fetal loss, congenital abnormalities, growth retardation, cancer, and neurobehavioral effects. These effects may operate through a variety of mechanisms including gene mutation, chromosomal aberrations, seminal fluid transfer of toxicants and epigenetic events.

Table of Contents:
Concepts and Mechanisms.- 1. Methods and Concepts in Detecting Abnormal Reproductive Outcomes of Paternal Origin.- Laboratory Evidence.- 2. Specific-Locus Mutation Tests in Germ Cells of the Mouse: An Assessment of the Screening Procedures and the Mutational Events Detected.- 3. Effects of Spermatogenic Cell Type on Quality of Mutations.- 4. Dominant Mutations in Mice.- 5. Aneuploidy Tests: Cytogenetic Analyses of Mammalian Male Germ Cells.- 6. Strategies for the Use of a Multiple-Endpoint System for Mammalian Germ Cell Mutation Testing.- 7. Transgenic Mice in Developmental Toxicology.- 8. Male Mice Receiving Very Low Doses of Ionizing Radiation Transmit an Embryonic Cell Proliferation Disadvantage to Their Progeny Embryos.- 9. Post-Testicular Mechanisms of Male-Mediated Developmental Toxicity.- Laboratory Evidence for Congenital Anomalies, Cancer and Neurobehavioral Outcomes.- 10. The Male-Mediated Developmental Toxicity of Cyclophosphamide.- 11. M ale-Mediated Teratogenesis: Ionizing Radiation/Ethylnitrosourea Studies.- 12. Preconception Exposure of Males and Neoplasia in Their Progeny: Effects of Metals and Consideration of Mechanisms.- 13. Male-Mediated Reproductive Toxicity: Effects on the Nervous System of Offspring.- Epidemiologic Findings.- 14. Paternal Occupation and Birth Defects.- 15. Male-Mediated Developmental Toxicity: Paternal Exposures and Childhood Cancer.- 16. Paternal Exposures and Pregnancy Outcome: Miscarriage, Stillbirth, Low Birth Weight, Preterm Delivery.- 17. Paternal Exposures and Embryonic or Fetal Loss: The Toxicologic and Epidemiologic Evidence.- 18. Reproductive Outcomes among Men Treated for Cancer.- 19. Genetic Effects of Atomic Bomb Exposure.- 20. Biological Factors Related to Male Mediated Reproductive and Developmental Toxicity.- 21. Antioxidant Prevention of Birth Defects and Cancer.- Risk Assessment and Policy Issues.- 22. Quantitative Risk Assessment for Paternally-Mediated Developmental Toxicity.- 23. Paternally-Mediated Developmental Toxicity: Implications for Risk Assessment and Science Policy.- 24. Physician and Patient Education.- 25. Characteristics of Male-Mediated Teratogenesis.- Abstracts.- 26. Aneuploidy Studies in Sperm: Post Meiotic Selection against Aneuploid Sperm.- 27. Association of Paternal and Maternal Exposure with Low Birth Weight and Preterm Births among Women Textile Workers.- 28. Genotoxic Consequences of Testicular Localization of Indium-114m.- 29. Male-Mediated Developmental and Reproductive Toxicity of Symm-Triazine Pesticides.- 30. National Transplantation Pregnancy Registry: Outcomes of Pregnancies Fathered by Male Transplant Recipients.- 31. Occupations of Fathers before Conception and the Risk of Testicular Cancer in Their Sons.- 32. Two-Dimensional Electrophoresis of Proteins: Detection and Characterization of Male-Mediated Developmental Toxicity.- Breakout Groups.- 33. Workshop Report on Mechanisms.- 34. Biomarkers and Health Endpoints of Developmental Toxicology of Paternal Origin: Summary of Working Group Discussions.- 35. Epidemiological Approaches.- 36. Laboratory Research Methods in Male-Mediated Toxicity.- 37. Physician and Patient Education.- 38. Risk Assessment and Risk Management.- 39. Multidisciplinary Approaches: Workshop Report.- Author Index.