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.

Chromosome Breakage in Human Preimplantation Embryos from Carriers of Structural Chromosomal Abnormalities in Relation to Fragile Sites, Maternal Age, and Poor Sperm Factors

“…Martin and Rademaker [1987] have reported an increased level of structural abnormalities in sperm in the form of chromosome breaks in the sperm of older males. More recently, Templado et al [2011] also reported an increase in unbalanced structural rearrangements (especially duplications) in the sperm of older men, with larger chromosomes displaying a higher rate of abnormalities, contributing to the evidence of an age effect on the level of damage seen in human spermatozoa, which could be associated with chromosome breakage seen in human preimplantation embryos. In this study, the overall paternal age was 38 years.…”

De novo deletions and duplications detected by array CGH: a study of parental origin in relation to mechanisms of formation and size of imbalance

“…21 Templado et al 22 found a higher rate of structural abnormalities in the sperm of older males (6.6%) compared with younger males (4.9%). We have previously shown that non-recurrent reciprocal translocations have a strong paternal bias and are associated with a significant increase in paternal age.…”

Molecular causes of aneuploidy in mammalian eggs

“…Wholechromosome losses or gains, which are the most relevant type of aneuploidy in oocytes, have been reported to occur at a rate of 4-5% in human sperm (Templado et al, 2011b;Lu et al, 2012). Interestingly, when chromosomal errors are seen with advanced paternal age, it is generally structural rearrangements rather than numerical changes that are observed -this has been suggested to be due to errors arising during spermatogonial stem cell division in the adult testis (Templado et al, 2011a). By contrast, aneuploidy rates in human eggs can be about 60% or higher (Fragouli et al, 2011;Kuliev et al, 2011) (Fig.…”