Bernard Robaire

Advances in Male Mediated Developmental Toxicity

Preface. Sponsors. List of Participants. Gender-Specificity of Gamete Susceptibilities to Exposures. 1. Female-Specific Reproductive Toxicities Following Preconception Exposure to Xenobiotics J.B. Bishop. 2. Overview of Male Mediated Developmental Toxicity D. Anderson. Exposures and Effects: Occupational and Environmental. 3. Epidemiologic Evidence on Biological and Environmental Male Factors in Embryonic Loss J.P. Bonde, et al. 4. Mechanisms of Male Mediated Developmental Toxicity Induced by Lead E.K. Silbergeld, et al. 5. Paternal Exposure to Known Mutagens and Health of the Offspring: Ionizing Radiation and Tobacco Smoke D.A. Savitz. 6. FISH (Fluorescence In Situ Hybridization) to Detect Effects of Smoking, Caffeine, and Alcohol on Human Sperm Chromosomes W.A. Robbins. Markers of Sperm Damage and Germ Line Genotoxicity. 7. Sperm Nuclear DNA Damage in the Human D. Sakkas, et al. 8. The Human Spermtozoon: Not Waving but Drowning J.R. Aitken, D. Sawyer. 9. Model Systems for Studying Germ Cell Mutagens: From Flies to Mammals E.W. Vogel, M.J.M. Nivard. 10. Germline Mutation Induction at Mouse and Human Tandem Repeat DNA Loci Y.E. Dubrova. 11. PAINT/DAPI Analysis of Mouse Zygotes to Detect Paternally Transmitted Chromosomal Aberrations F. Marchetti, A.J. Wyrobek. Exposures and Effects: Causes of Cancer Consequences of Treatment. 12. Paternal Occupation and Childhood Cancer A.F. Olshan, E. van Wijngaarten. 13. Radiation and Malformations in a Murine Model W.-U. Muller. 14. Mechanisms of Action of Cyclophosphamide asa Male-Mediated Developmental Toxicant B. Robaire, B.F. Hales. 15. Chromosome Abnormalities in Human Sperm R.H. Martin. Pregnancy Outcome. 16. Distinguishing Between Fertilization Failure and Early Pregnancy Loss When Identifying Male-Mediated Adverse Pregnancy Outcomes S.D. Perrault. 17. ICSI, Male Pronuclear Remodeling and Cell Cycle Checkpoints L. Hewitson, et al. 18. Increased Incidence of Malformations in the Offspring of Male Mice Prenatally Exposed to Synthetic Estrogens T. Nagao, et al. Strategies for Prevention. 19. Implications of Research in Male-Mediated Developmental Toxicity to Clinical Councellors, Regulators, and Occupational Safety Officers J.M. Friedman. 20. Restoration of Spermatogenesis after Exposure to Toxicants: Genetic Implications M.L. Meistrich, et al. Future Directions. 21. Epigenetics: Role of Germ Cell Imprinting M.S. Bartolomei. 22. Efficiency and Safety of Animal Cloning R. Yanagimachi. Workshop Reports. 23. Integrating New Tests of Sperm Genetic Integrity into Semen Analysis: Breakout Group Discussion S.D. Perreault, et al. 24. Risk Assessment A.F. Olshan, et al. 25. Study Designs for the Assessment of Male Mediated Developmental Toxicity B.F. Hales, D.C. Cyr. 26. Translational Research in Male Mediated Developmental Toxicity J.M. Trasler. Author Index. Subject Index.

Impact of the Chemotherapy Cocktail Used to Treat Testicular Cancer on the Gene Expression Profile of Germ Cells from Male Brown-Norway Rats

Abstract Advances in treatment for testicular cancer that include the coadministration of bleomycin, etoposide, and cisplatin (BEP) have brought the cure rate to higher than 90%%. The goal of this study was to elucidate the impact of BEP treatment on gene expression in male germ cells. Brown-Norway rats were treated for 9 wk with vehicle (0×) or BEP at doses equivalent to 0.3× and 0.6× the human dose. At the end of treatment, spermatogenesis was affected, showing altered histology and a decreased sperm count; spermatozoa had a higher number of DNA breaks. After 9 wk of treatment, round spermatids were isolated, and RNA was extracted and probed on Rat230–2.0 Affymetrix arrays. Of the 31u200a099 probe sets present on the array, 59%% were expressed in control round spermatids. BEP treatment significantly altered the expression of 221 probe sets, with at least a 1.5-fold change compared with controls; 80%% were upregulated. We observed a dose-dependent increase in the expression of oxidative stress response genes and no change in the expression of genes involved in DNA repair. BEP upregulated genes were implicated in pathways related to Jun and Junb protooncogenes. Increased mRNA levels of Jun and Junb were confirmed by quantitative RT-PCR; furthermore, JUN protein was increased in elongating spermatids. Thus, BEP exposure triggers an oxidative stress response in round spermatids and induces many pathways that may lead to the survival of damaged cells and production of abnormal sperm.

Chapter 11:Molecular Changes in Sperm and Early Embryos after Paternal Exposure to a Chemotherapeutic Agent

The consequences of exposure to drugs, radiation, and environmental toxicants on reproduction and development are a growing concern. The extent to which paternal exposures contribute to human infertility and pregnancy loss is unknown. Cyclophosphamide (CPA), a commonly used anticancer drug, remains ...

Targets of Chemotherapeutic Drug Action in Testis and Epididymis

Paternal occupational exposures to mercury, anaesthetic gases, lead, some solvents, and pesticides are associated with an increase in spontaneous abortions (1). Paternal occupations that include painters, auto mechanics, and firemen and involve exposure to metals, solvents, and pesticides are associated with birth defects (2). Adverse effects may not be apparent at birth; increased incidences of childhood cancer are found after a number of the same exposures as for birth defects (3).