Potential Future Applications

Because FISH analysis is simple and provides data on large sample sizes of sperm cells, it has been suggested as a technique for assessing the effects of potential mutagens on human sperm. We and others have studied cancer patients treated by chemotherapeutic agents and determined that these agents can cause a significant increase in the frequency of sperm chromosome abnormalities, particularly during chemotherapy and up to 2 years following treatment.[27-29]

The effects of pesticides have also been studied, as there is increasing concern about potential adverse consequences to reproduction and fertility. Two studies have not shown any association between pesticide use and sperm aneuploidy.[24,30] A third study did find an increased frequency of YY aneuploidy in pesticide factory workers exposed to higher pesticide concentrations.1-31-1

A number of infertility clinics have advocated the use of FISH analysis in clinical sperm samples from infertile patients. As mentioned above, infertile men certainly have an increased frequency of chromosome abnormalities in their sperm cells. Furthermore, studies have shown that specific men with an increased frequency of sperm chromosome abnormalities have fathered chromosomally abnormal pregnancies, for example, a man with a frequency of XY disomy 14 times higher than controls fathered a fetus with 47,XXY Klinefelter syndrome,[32] and men with an elevated frequency of disomy 21 sperm fathered children with Down syndrome (trisomy 21), shown to be paternally derived.[14] In addition, a number of studies have demonstrated that men with macrocephalic sperm have a very high frequency of sperm aneuploidy and diploidy.[33,34] Thus the addition of FISH analysis of sperm cells might be a useful investigation in male factor infertility, especially in cases known to have a high risk of abnormalities, such as men heterozygous for translocations or men with macrocephalic sperm cells.

Geographical and Ethnic Factors

Two laboratories have studied the frequency of sperm aneuploidy in geographically and ethnically diverse populations using the same experimental conditions, DNA probes, and scoring criteria. We found no difference in disomy frequencies for autosomes or sex chromosomes in nonsmoking, nonalcohol drinking Chinese men compared to Canadian men.[12] However, Rubes et al.[23] detected a significant increase in the frequency of sperm disomy in nonsmoking Czech men compared to Califor-nian men. Thus, further studies on different populations are required to determine if sperm aneuploidy frequencies differ in various groups.

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