Segregation of sex chromosomes into sperm nuclei in a man with 47,XXY Klinefelter's karyotype: a FISH analysis

Abstract

Meiotic segregation of the sex chromosomes was analysed in sperm nuclei from a man with Klinefelter's karyotype by three-colour FISH. The X- and Y-specific DNA probes were co-hybridized with a probe specific for chromosome 1, thus allowing diploid and hyperhaploid spermatozoa to be distinguished. A total of 2206 sperm nuclei was examined; 958 cells contained an X chromosome, 1077 a Y chromosome. The ratio of X:Y bearing sperm differed significantly from the expected 1:1 ratio (chi2 = 6.96; 0.001 < P < 0.01). Sex-chromosomal hyperhaploidy was detected in 2.67% of the cells (1.22% XX, 1.36% XY, 0.09% YY) and a diploid constitution in 0.23%. Although the frequency of 24,YY sperm was similar to that detected in fertile males, the frequencies of 24,XX, 24,XY and diploid cells were significantly increased. A sex-chromosomal signal was missing in 4.26% of the spermatozoa. This percentage appeared to be too high to be attributed merely to nullisomy for the sex chromosomes and was considered, at least partially, to be the result of superposition of sex-chromosomal hybridization signals by autosomal signals in a number of sperm nuclei. The results contribute additional evidence that 47,XXY cells are able to complete meiosis and produce mature sperm nuclei.

Chromosome studies in 1792 males prior to intra-cytoplasmic sperm injection: the Dutch experience

“…Preliminary data of FISH analysis on sperm of males with three sex chromosomes shows a small but significant increased frequency of hyperploid sperm as compared to the normal sperm (see for review Gutenbach and others). [17][18][19][20] In this study there were six cases of a structural Y-chromosome aberration (Table 2), an extremely rare occurrence in the normal newborn male population. In four cases we were unable to study the inheritance pattern of the aberration.…”

Ploidy of spermatogenic cells of men with non-mosaic Klinefelter’s syndrome as measured by a computerized cell scanning system

“…However, it is widely reported that men with KS have higher rates of sex and autosomal aneuploidy [5][6][7][8][9][10][11]. Two approaches on the ability of 47,XXY testes to yield postmeiotic cells exist.…”

“…They were reinforced by Egozcue et al [35] who identified the absence of 46,XY spermatogonia in patients negative for spermatids and spermatozoa, and by Mroz et al [36] who showed a clear absence of meiotic competence of 47,XXY cells in mice. Small quantities of studied germ cells such as 20-100 spermatogonia and primary spermatocytes in very few biopsies [1][2][3][4][5]8], as well as technical shortcomings, preclude a definite conclusion [1,4,17,19,20,23] (the study by Yamamoto et al [23] (2002) included 12 biopsies, but lacked information regarding the number of meiotic cells). The CCSS technique, which is based on corresponding size and morphology of the cells and their FISH images, enabled an extended study at three levels:…”

“…Theoretically, the expected rate of aneuploidy in the setting of 47,XXY meiosis is up to 50 % [46,47]. However, the percentages of aneuploidy values in the testes of KS men reported by others reached 10-20 % [5,8,9]. We found an elevation in the percentage of euploid cells after the first meiotic division along the final stages of spermatogenesis (from 8.4 % for spermatogonia, and 14.7 % in primary spermatocytes to 44.4 % post-meiotic round cells for positive cases).…”

“…In the other 50 %, no germ cells at all or different stages including post-meiotic cells with no mature figures might be present (KS negative). Although higher rates of sex and autosomal aneuploidy have been reported in positive KS patients [5][6][7][8][9][10][11], most offspring had a normal karyotype [12,13]. To date, only one fetus with the 47,XXY karyotype has been conceived and reduced in the 14th gestational week (from a triplet pregnancy) [14], and two other fetuses have been diagnosed as mosaic 46,XY/47,XXY karyotype by preimplantation genetic diagnosis (PGD) [15].…”