November/December 1995 in PDF format (1650K)
We have developed a powerful new tool using chromosome-specific DNA probes to study the causes of chromosomal abnormalities in sperm and their effects on embryonic development. The technique, fluorescence in situ hybridization (FISH), involves binding fluorescent labels to repetitive sequences of DNA in specific chromosomes. Its use in humans can provide valuable information on the sensitivity of sperm to environmental, occupational, and drug exposures as well as to other risk factors, including
age and genetic variation. Such factors can result in chromosomal abnormalities that may be passed on to the embryo and fetus. Our recent studies show that a small fraction of human sperm from healthy males contains genetic defects, specifically abnormal numbers of chromosomes (aneuploidies). The proportion of such defective sperm appears to increase with age and smoking. These findings are supported by preliminary results on the frequency of aneuploid sperm of mice, which appear to be good models for studying induced aneuploidy. Treatment of men with Hodgkin's disease using the chemotherapeutic drug NOVP induces a transient elevation in levels of aneuploid sperm.
We are developing animal models to better understand how defective sperm affect the survival and development of the early embryo. We are also beginning to study fathers of children born with chromosomal defects, such as Klinefelter syndrome, to ascertain whether these men produce more aneuploid sperm than do fathers of healthy children.
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