Cytogenetics of somatic cells and sperm from a 46,XY/45,X mosaic male with moderate oligoasthenoteratozoospermia.
ABSTRACT To determine aneuploidy frequencies in sperm from a patient with normal phenotype and 46,XY/45,X mosaicism in somatic cells (peripheral lymphocytes).
Infertility clinic and genetics laboratory.
A 30-year-old male with primary infertility and moderate oligoasthenoteratozoospermia.
Cytogenetic analysis of somatic cells and determination by fluorescence in situ hybridization of aneuploidy frequencies for the gonosomes (sex chromosomes) and chromosome 18 in sperm from whole and Percoll-separated semen.
Somatic and gametic aneuploidy were scored.
Analysis of lymphocyte metaphase cells showed a mosaic 46,XY (90%)/ 45,X (10%) karyotype. Significantly higher frequencies of gonosomal (semen, 1.92% versus 0.70%; Percoll, 1.12% versus 0.46%), and chromosome 18 (semen, 0.89% versus 0.28%; Percoll, 0.26% versus 0.10%) disomy were detected in the sperm of the patient compared with those observed in spermatozoa from a proved fertile control.
Significantly higher frequencies of aneuploid sperm suggest that the patient is at elevated risk of producing offspring with numerical chromosome abnormalities.
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ABSTRACT: A 47,XXY/46,XY male was investigated for the incidence of aneuploidy in sperm sex chromosomes using a three-colour X/Y/18 fluorescence in situ hybridisation (FISH) protocol. A total of 1701 sperm nuclei were analysed. The ratio of X-bearing to Y-bearing sperm did not differ from the expected 1 : 1 ratio although there were more 23,Y sperm than 23,X sperm (844 vs 795). There was a significantly increased proportion of disomy XY and XX sperm compared with normal controls (0.41% vs 0.10%, P < 0.001 and 0.29% vs 0.04%, P < 0.01). However, the incidence of YY sperm was similar to the controls (0.06% vs 0.02%). The diploidy rate was also significantly increased (1.7% vs 0.13%, P < 0.0001), as was disomy 18 (0.71% vs 0.01%) and 25,XXY (0.47% vs 0%). The results support the hypothesis that some 47,XXY cells are able to undergo meiosis and produce mature spermatozoa. Patients with mosaic Klinefelter syndrome with severe oligozoospermia have significantly elevated incidences of disomy XY and XX sperm and may be at a slightly increased risk of producing 47,XXX and 47,XXY offspring. Additionally, they may be at risk of producing offspring with autosomal trisomies. Hence, patients with Klinefelter mosaicism scheduled for intracytoplasmic sperm injection intervention should first undergo FISH analysis of their sperm to determine their risk.Human Genetics 01/1999; 104(5):405-409. · 4.63 Impact Factor
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ABSTRACT: Recent evidence suggests that infertile males donating semen for intracytoplasmic sperm injection (ICSI) may be at an increased risk of transmitting numerical (predominantly sex chromosome) abnormalities to their offspring. The present study was designed to determine aneuploidy in spermatozoa from oligoasthenoteratozoospermic (OAT) patients undergoing ICSI. Aneuploidy frequencies of 12 autosomes and the sex chromosomes were determined by fluorescence in-situ hybridization (FISH) on spermatozoa from fresh ejaculate of nine severe OAT patients and four proven fertile donors. FISH, using directly labelled (fluorochrome-dUTP) satellite or contig DNA probes specific for chromosomes 4, 6, 7, 8, 9, 10, 11, 12, 13, 17, 18, 21, X, and Y, was performed on decondensed spermatozoa. Per chromosome disomy frequencies for autosomes and sex chomosomes in OAT males were 0-5. 4%. In contrast, the disomy frequencies in controls were 0.05-0.2%. The frequency of diploid spermatozoa in OAT patients was 0.4-9.6%; controls showed a mean of 0.04%. Using recently developed formulae, the total aneuploidy in our OAT patient population was estimated to be 33-74%. In contrast, estimates of mean total aneuploidy in the spermatozoa of controls ranged from 4.1 to 7.7%, depending upon method of calculation. Six series of ICSI were performed on five of the OAT patients. Four resulted in no establishment of pregnancy; the others failed to establish ongoing pregnancies. Our cytogenetic data show significantly elevated frequencies of diploidy, autosomal disomy and nullisomy, sex chromosome aneuploidy, and total aneuploidy in OAT patients, which may contribute to the patients' infertility.Human Reproduction 06/1999; 14(5):1266-73. · 4.67 Impact Factor
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ABSTRACT: The objective was to estimate the risk for subfertile males with a constitutional sex chromosomal abnormality of transmitting such a chromosome abnormality to their children, conceived by intracytoplasmic sperm injection (ICSI). Semen samples were obtained from seven severely oligospermic ICSI candidates. Six of them had a numerical sex chromosomal abnormality, including mosaic 45,X/46,XY, mosaic 46,XY/47, XXY, 47,XXY (Klinefelter's syndrome), and 47,XYY. One male had a structural abnormality, namely, an inversion of the Y chromosome. The semen was studied by three-color fluorescent in situ hybridization (FISH) with probes specific for chromosomes 18,X, and Y. Chromosomal aneuploidy rates of any of the three chromosomes were significantly higher than the aneuploidy rates observed in three control samples but comparable to the rates observed in 10 ICSI candidates with oligoasthenoteratozoospermia (OAT) and a normal constitutional karyotype. Our data indicate that males with (mosaic) sex chromosomal abnormalities have no higher risk of producing offspring with a sex chromosomal abnormality by ICSI than OAT males with a normal karyotype.Journal of Assisted Reproduction and Genetics 04/2000; · 1.82 Impact Factor