Around 10% of sperm from a healthy human male carry visible chromosomal abnormalities. Despite the relevance of this striking statistic to the fertility of males in one generation, and the health of their progeny in the next, we know surprisingly little about the origins and causes of these sperm abnormalities. Sloter et al. have developed a fluorescence in situ hybridization (FISH) assay to detect specific chromosomal abnormalities in sperm — an assay that will provide new insight into the poor quality of human sperm.

Much of the previous analysis of chromosomal abnormalities in sperm has relied on the hamster-egg method. In this method, sperm are allowed to fuse with hamster oocytes, and when the sperm chromosomes enter metaphase, they are visualized by traditional cytogenetic staining methods. High frequencies of sperm chromosomal abnormalities have been detected in this assay, but it was always possible that the abnormalities seen at metaphase were induced after fusion.

Multicolour FISH methods for the direct analysis of human sperm have been developed over recent years and, in the latest work, Sloter et al. have devised an assay that can detect chromosomal breaks and aneuploidy on chromosome 1. Three separate probes are used that hybridize to different satellite DNA loci — two near the centromere (1cen, labelled red and 1q12, blue) and one at the tip of the short arm of the chromosome (1p36, green).

The authors have catalogued a range of chromosomal defects in the mature sperm of four healthy males. In the image (courtesy of A. J. Wyrobek), evidence for a break within the 1q12 chromosomal region is shown. The current assay focuses on one region of the genome, but extrapolation to the whole genome yields an estimate for the number of chromosomal abnormalities in sperm that agrees with previous hamster-egg studies — around 8%. Structural abnormalities, such as chromosomal breaks, tend to occur more frequently than aneuploidy. The position of the breaks could also be assessed, and evidence for chromosomal hotspots (which varied from one individual to the next) was detected. This and other FISH-based assays now set the scene for more detailed analyses of the genetic and environmental factors that influence the occurrence of sperm chromosomal abnormalities.