Aneuploidy in Human Spermatozoa

Abstract

We reviewed the frequency and distribution of disomy in spermatozoa obtained by multicolor-FISH analysis on decondensed sperm nuclei in (a) healthy men, (b) fathers of aneuploid offspring of paternal origin and (c) individuals with Klinefelter syndrome and XYY males. In series of healthy men, disomy per autosome is approximately 0.1% but may range from 0.03 (chromosome 8) to 0.47 (chromosome 22). The great majority of authors find that chromosome 21 (0.18%) and the sex chromosomes (0.27%) have significantly elevated frequencies of disomy although these findings are not universal. The total disomy in FISH studies is 2.26% and the estimated aneuploidy (2× disomy) is 4.5%, more than double that seen in sperm karyotypes (1.8%). Increased disomy levels of low orders of magnitude have been reported in spermatozoa of some normal men (stable variants) and in men who have fathered children with Down, Turner and Klinefelter syndromes. These findings suggest that men with a moderately elevated aneuploidy rate may be at a higher risk of fathering paternally derived aneuploid pregnancies. Among lifestyle factors, smoking, alcohol and caffeine have been studied extensively but the compounding effects of the 3 are difficult to separate because they are common lifestyle behaviors. Increases in sex chromosome abnormalities, some autosomal disomies, and in the number of diploid spermatozoa are general features in 47,XXY and 47,XYY males. Aneuploidy of the sex chromosomes is more frequent than aneuploidy of any of the autosomes not only in normal control individuals, but also in patients with sex chromosome abnormalities and fathers of paternally derived Klinefelter, Turner and Down syndromes.

Reduction in sperm aneuploidy levels in severe oligoasthenoteratospermic patients after medical therapy: a preliminary report

“…spermatozoa per patient). As expected (see the 'Materials and methods' section), some patients (22) exhibited a significant reduction in sperm aneuploidy levels coincident with drug administration, and some patients (11) exhibited levels of sperm aneuploidy that did not change during the drug course.…”

“…Other authors maintain that sperm aneuploidy levels are likely to be inversely related to sperm morphology, sperm motility or sperm concentration. 12,22 However, the computerized cell scanning system has demonstrated the relationship between chromosomal aberrations and sperm morphology in the same spermatozoon. 23 Furthermore, the studies supporting a relationship between sperm aneuploidy levels and sperm motility or sperm concentration contain methodological biases; namely, only a small number of patients were tested and/or few (one to three) autosomes1XY chromosomes were assessed and/or the statistical analyses used were based on thresholds, whereas sperm concentration, motility and morphology, and the percentage of aneuploid spermatozoa are continuous variables.…”

Case report: elevated sperm aneuploidy levels in an infertile Robertsonian translocation t(21;21) carrier with possible interchromosomal effect

“…An average diploidy rate of 0.2% and a mean disomy frequency of 0.18% were described for healthy individuals. However, chromosome-specific differences are evident [12], for example when comparing chromosome 200.08% and chromosome 2200.42%) (Fig. 1).…”

Recurrent Miscarriage: A Review

“…Approximately 70% of fetal trisomies are of maternal origin and caused by a mal-segregation event in the first meiotic division. In contrast, sex chromosomal aneuploidies can more frequently be traced back to the father (50% of 47, XXY, 100% of 47, XYY and 70%-80% of 45, X) [3,8,25].…”

“…During the last two decades, numerous Fluorescence In Situ Hybridization (FISH) studies to interphase nuclei of human spermatozoa ("sperm-FISH") have elucidated nondisjunction mechanisms and frequencies in male germ cells [25]. However, few data were available regarding aneuploidy in spermatozoa from men in couples with RM or the associated risk of spontaneous miscarriage, because only a small number men affected of RM had been analyzed; most of these analyses had been limited to chromosomes 13, 18, 21, X and Y.…”