Advanced age increases chromosome structural abnormalities in human spermatozoa

Abstract

This study explores the relationship between sperm structural aberrations and age by using a multicolor multichromosome FISH strategy that provides information on the incidence of duplications and deletions on all the autosomes. ToTelvysion kit (Abbott Molecular, Abbott Park, IL, USA) with telomere-specific probes was used. We investigated the sperm of 10 male donors aged from 23 to 74 years old. The donors were divided into two groups according to age, a cohort of five individuals younger than 40 and a cohort of five individuals older than 60 years. The goal of this study was to determine (1) the relationship between donor age and frequency and type of chromosome structural abnormalities and (2) chromosomes more frequently involved in sperm structural aberrations. We found that the older patients had a higher rate of structural abnormalities (6.6%) compared with the younger cohort (4.9%). Although both duplications and deletions were seen more frequently in older men, our findings demonstrate the presence of an excess of duplications versus deletions in both groups at a ratio of 2 to 1. We demonstrate that the distribution of duplications and deletions was not linear along the chromosomes, although a trend toward a higher rate of abnormalities in larger chromosomes was observed. This work is the first study addressing the frequencies of sperm chromosome structural aberrations of all autosomes in a single assay thus making a contribution to the clarification of the amount and origin of damage present in human spermatozoa and in relation to age.

Figure 1

The 15 aliquots of the FISH probe panel used showing both the chromosome location and the color of the probes (spectrum orange, spectrum green and spectrum aqua) from each aliquot.

Figure 2

FISH in human decondensed sperm nuclei using one of the 15 mixtures of the FISH panel (mixture 12) showing structural aberrations for chromosome 12: deletions for subtelomere 12p and duplications for subtelomeres 12p and 12q.

Figure 3

(a) Percentage of chromosome structural abnormalities per chromosome in each group of age. (b) Percentage of duplications per chromosome.(c) Percentage of deletions per chromosome.