Paternal Age and Numerical Chromosome Abnormalities in Human Spermatozoa

Abstract

This study explores the relationship between numerical chromosome abnormalities in sperm and age in healthy men. We performed FISH in the spermatozoa of 10 donors from the general population: 5 men younger than 40 years of age and 5 fertile men older than 60 years of age. For each chromosome, 1,000 sperm nuclei were analyzed, with a total of 15,000 sperm nuclei for each donor. We used a single sperm sample per donor, thus minimizing intra-donor variability and optimizing consistent analysis. FISH with a TelVysion assay, which provides data on aneuploidy of 19 chromosomes, was used in order to gain a more genome-wide perspective of the level of aneuploidy. Aneuploidy and diploidy rates observed in the younger and older groups were compared. There were no significant differences in the incidence of autosomal disomy, sex chromosome disomy, total chromosome disomy, diploidy, nor total numerical abnormalities between younger and older men. This work confirms that aneuploidy of the sex chromosomes is more common than that of autosomes and that this does not change with age. Our results suggest that some probe combinations have a tendency to indicate higher levels of diploidy, thus potentially affecting FISH results and highlighting the limitations of FISH.

Meiotic nondisjunction and sperm aneuploidy in humans

“…To date, a handful of studies have examined whether advancing paternal age contributes to sperm aneuploidy. The majority of these provide little evidence to support a correlation between advancing paternal age and increased levels of sperm aneuploidy (Fonseka & Griffin 2011, Andreescu et al 2016, Donate et al 2016. There may be a very small effect for a handful of chromosomes in much later years, typically decades after what would traditionally be considered 'reproductive age' (Griffin et al 1995, Fonseka & Griffin 2011, Garcia- Ferreyra et al 2018).…”

Evaluation of the impact of sperm morphology on embryo aneuploidy rates in a donor oocyte program

“…Abnormal chromosomal segregation occurring during meiosis can lead to aneuploidy in both male and female gametes by deleting or including an extra copy of chromosomes (Hassold and Hunt 2001;Lamb et al 2005). Nevertheless, there is a difference in frequency of aneuploidy observed in spermatozoa (~4.5%) and oocytes (~20%) (Donate et al 2016). The difference in the incidence of aneuploidy among the male and female gametes can be attributed to the earlier completion of meiosis in the spermatozoa than its counterpart, and that it is equipped with more effective check-points before fertilization.…”

Paternal age and assisted reproductive technology: problem solver or trouble maker?

“…In a study evaluating numeric chromosomal abnormalities in sperm of semen donors, no differences were observed in older men (aged 60-74, mean age 66.4 years) when compared to younger counterparts (aged 23-37, mean age 27.8 years). 55 In other study comparing sperm aneuploidy rates between infertile men with oligoasthenoteratozoospermia (OAT) and fertile men, Andreescu et al did not find any differences in aneuploidy rates with increasing paternal age. 56 The authors showed, however, that sperm from OAT patients exhibited higher rates of aneuploidy than fertile men, with increased nullisomy or disomy of chromosomes 13, 18, 21, X, and Y.…”