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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"The variability in published results across laboratories may reflect differences in hybridization and scoring methodologies, differences in numbers of men evaluated , number of samples, and number of cells scored per sample. Within laboratories, however, a downward trend in disomy frequencies was noted in all studies using semen donated from healthy men when enriched fractions were compared with sperm remaining in the pellet (Martínez-Pasarell et al, 1997; Newberg et al, 1998; Pfeffer et al, 1999). "
[Show abstract][Hide abstract] ABSTRACT: Toxicological and epidemiological studies have investigated several factors that are believed to induce cytogenetic damage in human sperm cells in an effort to estimate heritable risk to future generations. Most of these studies have not differentiated damage based on cell fertility or motility. In the clinical setting, intracytoplasmic sperm injection (ICSI) bypasses the natural process of sperm selection. Although practitioners attempt to select motile sperm for ICSI, the sperm may not always demonstrate motility, maturity, or even viability. Knowing whether cytogenetic damage differs in motile versus unselected sperm would improve our ability to estimate heritable risk and lead to improved ICSI procedures, and would expand the body of toxicology and epidemiology research. We divided semen samples from 20 healthy donors and compared aneuploidy and chromosome breakage in sperm cells gathered directly from the ejaculate (unprocessed semen) with cells enriched for motility using the swim-up assay. Sperm fluorescence in situ hybridization was used to detect aneuploidy for chromosomes 13, 18, 21, X, and Y. Tandem labeling probes were used to detect breakage in the 1cen-1q12 region of chromosome 1. The occurrence of disomy 18-18 and XY18 was significantly lower in specimens enriched for motility (P = .004 and P = .001, respectively). Sperm that carried duplication errors and diploid sperm were also seen less frequently in semen analyzed by the swim-up assay (P < .008). Chromosome 1 breakage did not differ between swim up-assayed and unprocessed specimens. Findings suggest that unprocessed semen may overestimate heritable aneuploidy risk in sperm biomarker studies, and may be biologically relevant to ICSI in disomy categories 18-18 and XY18, demonstrating 1.4-fold to 1.8-fold differences.
Full-text · Article · Mar 2002 · Journal of Andrology
"Sperm karyotypes showed a significant increase in the frequency of numerical abnormalities relative to controls. Newberg et al. (1998) showed significantly higher frequencies of disomy for chromosomes 18, X and Y in spermatozoa from a male with moderate OAT and somatic cell mosaicism: 46,XY (90%)/45,X (10%). In't Veld et al. performed molecular cytogenetic analysis on spermatozoa from 1267 a male with OAT (In't Veld et al., 1997). "
[Show abstract][Hide abstract] 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.
Full-text · Article · Jun 1999 · Human Reproduction
[Show abstract][Hide abstract] 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.