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-Specific Links

Final Progress Reports

Year:   2005 

The long-term objectives of this research are to understand the mechanisms of male-mediated developmental toxicity and to evaluate the impact of common host factors on the rates of physiological, genetic, and chromosomal defects in human sperm. Drs. Eskenazi and Wyrobek’s practical goal was to develop a validated panel of sperm biomarkers for use in epidemiological studies to measure the effect of exposure to Superfund agents as predictors of male infertility and heritable genetic diseases affecting the health of their offspring.

During the past year, project investigators conducted a study on the effects of benzene exposure on human sperm in collaboration with the Chinese Center for Disease Control and Prevention in Beijing, and the Tianjin Occupational Disease Hospital in Tianjin. A detailed interview, physical exam, and semen, blood, urine, and air badge samples were collected from 34 benzene-exposed male factory workers and 44 controls. Laboratory analyses using the investigator’s panel of sperm biomarkers are in progress. They also plan to compare the chromosome damaging effects of benzene in blood and sperm from the same individuals.

To establish a foundation for epidemiological investigations of male exposure to Superfund agents, it was important to understand the effects of age, diet and other common host factors on sperm quality and the incidence of genomic damage in sperm. The investigators demonstrated that male age was associated with decreased semen quality (sperm numbers and motility), and increases in various types of sperm genomic damage including DNA fragmentation, alkali-labile DNA sites, structural chromosome aberrations, and base-pair mutations in achondroplasia and Apert genes. However, age was not associated with sperm aneuploidy or with double-strand DNA breaks in sperm. These results indicate that men also have “biological clocks” that may increase the risks of older men for transmitting genomic defects that would be harmful to the health of their offspring.

Project investigators have also found that intake of common antioxidants and micronutrients can modify semen quality and the incidence of genomic damage in sperm. Using food intake measured by a Food Frequency Questionnaire (FFQ), they found that (a) antioxidant intake was associated with increased sperm motility, but not sperm DNA fragmentation; (b) high folate intake was associated with lower levels of certain aneuploidies; and (c) high vitamin C intake was related to decreased alkali labile DNA sites. By measuring the levels of zinc, folate, alpha and gamma tocopherol in seminal plasma and levels of zinc and other elements in sperm, they found that seminal zinc was inversely associated with single and double strand DNA breaks in sperm and that the sperm of older men have significantly higher levels of zinc, copper, and calcium compared to younger men. Ongoing studies will relate the levels of micronutrients in seminal plasma and sperm with these and other measures of physiologic and genomic damage in sperm, controlling for age.

Project investigators’ age and micronutrient findings indicate the importance of controlling for male age and dietary intake in the design of epidemiological studies of human male exposures to agents that may be potential germ-cell mutagens.