Superfund Research Program
Determinants for Chromosomally Defective Human Sperm
Project Leaders: Andrew J. Wyrobek (Lawrence Livermore National Laboratory), Brenda Eskenazi
Grant Number: P42ES004705
Funding Period: 2000 - 2006
- Project Summary
Project Summary (2000-2006)
Exposure of fathers to environmental toxicants is associated with adverse consequences to the fetus and offspring. This project is investigating the roles of specific paternal host factors and environmental risk factors for transmission of chromosomal defects via sperm. Two promising sperm FISH methods have been developed to detect human sperm carrying abnormal numbers of chromosomes (aneuploidy) or structurally defective chromosomes (partial chromosomal duplications, deletions, or breakage). Studies with these sperm methods indicate that chromosomally defective sperm are inducible after exposures to certain drugs, both in murine and human studies; however, the utility of the genetic biomarkers in sperm for the assessment of reproductive hazards in occupationally or environmentally exposed populations remains to be proven. In addition, the modifying effects of host factors are not known. In this study, the relationship of age and diet on sperm chromosomal defects in healthy non-smoking men is being investigated to determine if occupational exposure to benzene is associated with increases in the proportions of chromosomally defective sperm and with reduced semen quality. The sperm from approximately 100 healthy men age 20-80, will be characterized to determine age effects on chromosome structure in sperm, and to examine associations between diet and chromosomally abnormal sperm. Occupational exposure to benzene will be evaluated in a Chinese cohort. Research will focus on benzene because it is an important Superfund chemical and a proven human leukemogen, and occupational exposure induces chromosomal damage in lymphocytes.