Assessment of sex chromosome aneuploidy in sperm nuclei from 47,XXY and 46,XY/47,XXY males: comparison with fertile and infertile males with normal karyotype

Abstract

Sex chromosome aneuploidy was assessed in spermatozoa from a 47,XXY male and a 46,XY/47,XXY male using three colour fluorescence in-situ hybridization (FISH) and compared with two control groups. The first group included subjects of proven fertility and the second infertile males with normal constitutional karyotype. The frequencies of XX and YY disomic, XY hyperhaploid and diploid spermatozoa were significantly increased in the 47,XXY male compared to subjects from the two control groups (P < 0.0001). For the 46,XY/47,XXY sample, the same results were observed, except that the incidence of YY disomic spermatozoa did not differ significantly from the rate obtained in infertile patients. The frequency of sex chromosome aneuploidy did not differ significantly between the 47,XXY and the 46,XY/47,XXY males, except for XX disomic sperm nuclei which was higher in the 47,XXY patient. The frequency of chromosome 12 disomy was also increased in the two XXY individuals (0.42 and 0.49% respectively; P < 0.0001). The meiotic abnormalities observed in the two XXY patients arose through segregation errors in XY germ cells. The increased number of meiotic non-disjunctions observed in the germ cells of infertile males may be a common feature of the deficient oligo- or azoospermic testis. Patients with Klinefelter's syndrome with oligozoospermia have an increased risk of both sex chromosome and autosome aneuploidy in their progeny.

Chromosomal abnormalities in men with pregestational and gestational infertility in northeast China

“…Klinefelter's syndrome accounted for 5.04 % of all infertile males, and 97.45 % of Klinefelter patients had AS, as did four out of six cases with karyotypes 46,XY/47,XXY. These findings are in accordance with previous reports where focal spermatogenesis failure and severe OS were found in cases with 46,XY(X)/47,XXY mosaic karyotypes [15]. The current study further supports the theory that a superabundance of X chromosomes could affect the male-determining function by inhibiting maturity, hence promoting degenerative changes in the testis convoluted tubule and thus affecting spermatogenesis, ultimately resulting in varying degrees of related androgen dysfunctions [13].…”

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

“…CCSS enables a maximal sampling of the whole extracted tissue while screening dozens of testicular cell, including post-meiotic cells, with a high level of confidence [25,26] and a screening of more than 1,000 spermatogonia and 900 primary spermatocytes for each of the 11 biopsy samples. As expected, based on lymphocyte karyotypes in non-mosaic KS men, and similar to Rives et al [11] and Yamamoto et al [23], who identified between 88.5 and 100 % 47,XXY spermatogonia in testicular biopsies, we found around 90 % spermatogonia with 47,XXY and 10 % with 46,XY, independently of whether or not patients produced testicular sperm. It needs to be specified that Yamamoto et al [23] did not observe any testicular XY cells in negative cases.…”

“…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.…”

“…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].…”

Unsuspected Klinefelter Syndrome Diagnosed during Oncologic Evaluation: A Case Series

“…In these cases, there is an increased likelihood of having a child with a chromosomal imbalance involving the X chromosome. [17][18][19] New developments in assisted reproductive technologies, such as testicular sperm extraction and intracytoplasmic sperm injection, may offer men with nonmosaic KS and their partners the possibility of conception. 20 However, healthy deliveries after these procedures are rare, and concern regarding the possibility of transmitting chromosomal abnormalities exists.…”