Aneuploid spermatozoa in infertile men: teratozoospermia.

We and others have demonstrated that infertile men who are candidates for intracytoplasmic sperm injection (ICSI) have an increased frequency of chromosomal abnormalities in their sperm. Reports based on prenatal diagnosis of ICSI pregnancies have confirmed the increased frequency of chromosomal abnormalities in offspring. Most studies to date have lumped various types of infertility together. However, it is quite likely that some subsets of infertility have an increased risk of sperm chromosomal abnormalities whereas others do not. We have studied nine men with severe teratozoospermia (WHO, 1992 criteria, 0-13% morphologically normal forms) by multicolour fluorescence in situ hybridisation (FISH) analysis to determine if they have an increased frequency of disomy for chromosomes 13, 21, XX, YY, and XY, as well as diploidy. All of the men also had aesthenozoospermia (< 50% forward progression) but none of the men had oligozoospermia (<20 x 10(6) sperm/ml). The patients ranged in age from 20 to 49 years (mean 33.2 years) in comparison to 18 normal control donors who were 23 to 58 years (mean 35.6 years). The control donors had normal semen parameters and no history of infertility. A total of 180,566 sperm were scored in the teratozoospermic men with a minimum of 10,000 sperm analyzed/donor/chromosome probe. There was a significant increase in the frequency of disomy in teratozoospermic men compared to controls for chromosomes 13 (.23 vs.13%), XX (.13 vs.05%), and XY (.50 vs.30%) (P <.0001, 2-tailed Z statistic). This study indicates that men with teratozoospermia and aesthenozoospermia but with normal concentrations of sperm have a significantly increased frequency of sperm chromosomal abnormalities.     

Human sperm chromosome complements in chemotherapy patients and infertile men

Our studies of human sperm karyotypes and interphase sperm analyzed by fluorescence in situ hybridization (FISH) have both yielded estimates of disomy frequencies of approximately 0.1% per chromosome with an overall aneuploidy frequency in human sperm of approximately 5%–6%. However, the distribution of aneuploidy in sperm is not even, as our data from sperm karyotypes and multicolour FISH analyses both demonstrate a significant increase in the frequency of aneuploidy for chromosome 21 and the sex chromosomes. We have studied men at increased risk of sperm chromosomal abnormalities including cancer patients and infertility patients. Testicular cancer patients were studied before and 2–13 years after chemotherapy (CT) with BEP (bleomycin, etoposide, cisplatin). Sperm karyotype analysis on 788 sperm demonstrated no significant difference in the frequency of numerical or structural chromosomal abnormalities post-CT vs pre-CT. Similarly, multicolour FISH analysis for chromosomes 1, 12, XX, YY and XY in 161,097 sperm did not detect any significant differences in the frequencies of disomy before and after treatment. However, recent evidence has suggested a significant increase in the frequency of disomy and diploidy during CT. We have found that infertile men, who would be candidates for intracytoplasmic sperm injection, have an increased frequency of chromosomally abnormal sperm karyotypes. Also, FISH analysis for chromosomes 1, 12, 13, 21, XX, YY and XY in 255,613 sperm demonstrated a significant increase in chromosomes 1, 13, 21, and XY disomy in infertile men compared with control donors. Received: 4 July 1998; in revised form: 7 September 1998 / Accepted: 8 September 1998     

A comparison of the frequency of sperm chromosome abnormalities in men with mild,moderate, and severe oligozoospermia

Infertile men undergoing intracytoplasmic sperm injection have an increased frequency of chromosome abnormalities in their sperm. Men with low sperm concentration (oligozoospermia) have an increased risk of sperm chromosome abnormalities. This study was initiated to determine whether men with severe oligozoospermia (<10(6) sperm/ml) have a higher frequency of chromosome abnormalities in their sperm compared with men with moderate (1-9 x 10(6) sperm/ml) or mild (10-19 x 10(6) sperm/ml) oligozoospermia. Multicolor fluorescence in situ hybridization analysis was performed using DNA probes specific for chromosomes 13, 21, X, and Y (with chromosome 1 as an autosomal control for the sex chromosomes). Aneuploidy and disomy frequencies were assessed from a total of 603,011 sperm from 30 men: 10 in each of the categories. The mean frequencies of disomy for the patients with mild, moderate, and severe oligozoospermia were 0.17%, 0.24%, and 0.30%, respectively, for chromosome 13 and 0.22%, 0.44%, and 0.58%, respectively, for chromosome 21. For the sex chromosomes, the mean frequencies of disomy for mild, moderate, and severe oligozoospermia were 0.25%, 1.04%, and 0.68%, respectively, for XY, 0.047%, 0.08%, and 0.10%, respectively, for XX, and 0.04%, 0.06%, and 0.09%, respectively, for YY. The frequencies for diploidy also increased from 0.4% for mild to 1.20% for moderate to 1.24% for severe oligozoospermia. There was a significant inverse correlation between the frequency of sperm chromosome abnormalities and the sperm concentration for XY, XX, and YY disomy and diploidy. These results demonstrate that men with severe oligozoospermia have an elevated risk for chromosome abnormalities in their sperm, particularly sex chromosome abnormalities.     

Frequency and distribution of chromosome abnormalities in human spermatozoa

This study reviews the frequency and distribution of numerical and structural chromosomal abnormalities in spermatozoa from normal men obtained by the human-hamster system and by multicolor-FISH analysis on decondensed sperm nuclei. Results from large sperm karyotyping series analyzed by chromosome banding techniques and results from multicolor FISH in sperm nuclei (of at least 10(4) spermatozoa per donor and per probe) were reviewed in order to establish baseline values of the sperm chromosome abnormalities in normal men. In karyotyping studies, the mean disomy frequency in human sperm is 0.03% for each of the autosomes, and 0.11% for the sex chromosomes, lower than those reported in sperm nuclei by FISH studies using a similar methodology (0.09% and 0.26%, respectively). Both types of studies coincide in that chromosome 21 and sex chromosomes have a greater tendency to suffer segregation errors than the rest of the autosomes. The mean incidence of diploidy, only available from multicolor FISH in sperm nuclei, is 0.19%. Inter-donor differences observed for disomy and diploidy frequencies among FISH studies of decondensed sperm nuclei using a similar methodology could reflect real differences among normal men, but they could also reflect the subjective application of the scoring criteria among laboratories. The mean frequency of structural aberrations in sperm karyotypes is 6.6%, including all chromosome types of abnormalities. Chromosome 9 shows a high susceptibility to be broken and 50% of the breakpoints are located in 9q, between the centromere and the 9qh+ region. Structural chromosome aberrations for chromosomes 1 and 9 have also been analyzed in human sperm nuclei by multicolor FISH. Unfortunately, this assay does not allow to determine the specific type of structural aberrations observed in sperm nuclei. An association between advancing donor age and increased frequency of numerical and structural chromosome abnormalities has been reported in spermatozoa of normal men.     

Aneuploidy frequency in sperm of fertile men

Analysis of sperm aneuploidy in 11 healthy men using two-or three-color FISH permitted to determine the average frequency of disomy for chromosomes 13 and 21 (0.11% and 0.2%, respectively), disomy for chromosome 18 (0.05%) and to reveal gonosomal aneuploidy variants and their frequency. The frequency of XX disomy was 0.04%; XY, 0.17%; YY, 0.06%; and gonosomal nullisomy, 0.29%. We assessed the frequency of meiotic nondisjunction of 13, 21, 18, X, and Y chromosomes and the frequency of XX, XY, and YY diploid spermatozoa. The XY variant prevailed in gonosomal aneuploidy and diploidy and was associated with abnormal chromosomal segregation in meiotic anaphase I. The contribution of human sperm chromosomal imbalance to early embryonic lethality and to some forms of chromosomal abnormalities in the off-spring is discussed.     

Analysis of aneuploidy frequencies in sperm from patients with hereditary nonpolyposis colon cancer and an hMSH2 mutation

Hereditary nonpolyposis colon cancer (HNPCC) has been shown to be caused by mutations in the mismatch repair genes hMSH2, hMLH1, hPMS1, and hPMS2. Recent evidence has demonstrated that mutations in mismatch repair genes disrupt meiosis in mice. A large HNPCC kindred in Newfoundland, Canada, has an hMSH2 mutation-an A-->T transversion at the +3 position of the splice-donor site of exon 5. We have studied sperm from men with this hMSH2 mutation, since it is possible that mismatch repair mutations in humans might also have an effect on meiosis and normal segregation of chromosomes. The frequencies of aneuploid and diploid sperm were determined in 10 men with the hMSH2 mutation, by use of multicolor FISH analysis for chromosomes 13, 21, X, and Y. A minimum of 10,000 sperm per man was studied per chromosome probe. Control individuals consisted of men in the same kindred with HNPCC who did not carry the mutation and of other normal men from Newfoundland. A total of 321,663 sperm were analyzed: 200,905 sperm were from men carrying the hMSH2 mutation and 120,758 sperm were from control men. There was a significantly increased frequency of disomy 13, disomy 21, XX, and diploidy in mutation carriers compared with control men. These results suggest that the hMSH2 mutation may affect meiosis in humans.     

Aneuploidy in human sperm: a review of the frequency and distribution of aneuploidy, effects of donor age and lifestyle factors

Application of fluorescence in situ hybridization (FISH) analysis has opened the way for comprehensive studies on numerical chromosome abnormalities in human sperm. During the last decade, more than five million sperm from approximately 500 normal men were analyzed by a number of laboratories from around the world by this approach. Except for chromosome 19 which has been analyzed in only one study, all other chromosomes have been examined by two or more studies with considerable differences in disomy frequency for an individual chromosome among studies. The mean disomy frequency is 0.15% for each of the autosomes and 0.26% for the sex chromosomes. Most chromosomes analyzed have an equal distribution of disomy with the exception of chromosomes 14, 21, 22 and the sex chromosomes, which display significantly higher disomy frequencies. Slight but significant increases in disomy frequency with advancing paternal age were observed for some chromosomes, in particular for the sex chromosomes. Some lifestyle factors such as smoking, alcohol drinking and caffeine consumption have been investigated and no consistent association between disomy frequency and any type of lifestyle factors has been established. The question of whether different geographic and ethnic groups of men have inherent differences in frequency of disomic sperm has been investigated by two studies with conflicting results.     

Numerical chromosome abnormalities in spermatozoa of fertile and infertile men detected by fluorescence in situ hybridization

Fluorescence in situ hybridization (FISH) with single-color chromosome-specific probes was used to study the rates of disomy for chromosome 1, 16, X, and Y in sperm of fertile and infertile subjects. Diploidy rates were studied using a two-color cocktail of probes for chromosomes 17 and 18 in the same sperm samples. Two-color methodology was not available at the outset of the study. A total of 450,580 spermatozoa were studied from 21 subjects (9 fertile, 12 infertile). Significant differences were observed in the disomy rates between chromosomes with the highest frequency observed for chromosome 16 (0.17%) and the lowest for the Y chromosome (0.10%). No differences were observed between fertile and infertile subjects for either diploidy or disomy. Total disomy rates for chromosomes 1, 16, X and Y ranged from 0.34% to 0.84% among infertile subjects, and 0.32% to 0.61% among fertile subjects. Our data suggest that generalized aneuploidy in sperm is not a major contributor to unexplained infertility.     

Nondisjunction in human sperm: comparison of frequencies in acrocentric chromosomes.

Acrocentric chromosomes may be particularly predisposed to nondisjunction because of the frequency of trisomy for these chromosomes in human spontaneous abortions and liveborns. Studies of aneuploidy in human sperm have provided data on only a few acrocentric chromosomes, with evidence that chromosome 21 has a significantly increased frequency of disomy. To determine whether other acrocentric chromosomes have a higher frequency of nondisjunction or if chromosome 21 is anomalous, disomy frequencies for chromosomes 13 and 22 were studied by fluorescence in situ hybridization (FISH) analysis of 51,043 sperm nuclei from five normal men for whom the frequency of disomy for chromosomes 15 and 21 was known. The mean frequency of disomy for chromosome 13 (0.19%) did not differ significantly from that for other autosomes; however, the frequency of disomy 22 (1.21%) was significantly elevated (P < 0.001, Mantel-Haenszel chi(2) test). The G-group chromosomes (Nos. 21 and 22) also showed a significantly increased frequency of disomy (0. 75%) compared to acrocentric D-group chromosomes (viz., chromosomes 13 and 15; 0.15%) (P < 0.001, Mantel-Haenszel chi(2) test) and other autosomes (chromosomes 1, 2, 4, 9, 12, 13, 15, 16, 18, and 20; 0. 13%) studied in the same men (P < 0.001, Mantel-Haenszel chi(2) test).     

Relationship between clinical phenotype, semen parameters and aneuploidy frequency in sperm nuclei of 50 infertile males

The purpose of this study was to analyse the frequency of disomy for chromosomes 1, 13, 14, 18, 21, 22, X and Y in sperm nuclei of 50 infertile men and 10 healthy probands of proven fertility. Semen parameters (sperm count, global motility and morphology), urological clinical examination, genital ultrasound and lymphocyte karyotyping were performed for each patient. Disomy frequency was established by fluorescence in situ hybridization by using whole chromosome paint probes. The mean rate of disomy for the various autosomes studied was higher in infertile males than in subjects of proven fertility. Interchromosomal and interindividual differences in the disomy frequency were observed between the 50 patients. The mean frequency of homodisomy YY and heterodisomy XY was increased in spermatozoa of patients with low semen quality parameters (0.24% and 0.54%, respectively). The disomy frequency in infertile males was directly correlated with the severity of oligospermia. However, no relationship was established between aneuploidy rate, sperm motility, morphology or clinical phenotype. These results support the hypothesis that, during spermatogenesis of males with sperm parameter alterations, a decreased frequency of meiotic chromosome pairing and crossing over may lead to spermatogenesis arrest at the meiosis stage and/or to an increase of meiotic nondisjunctions. Meiotic arrest in some germ cells may be responsible for oligospermia and nondisjunctions in other cells for aneuploidy in mature male gametes.     

Aneuploidy in human spermatozoa

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.     

Analysis of aneuploidy for chromosomes 13, 21, X and Y by multicolour fluorescence in situ hybridisation (FISH) in a 47,XYY male.

The frequency of aneuploid sperm was assessed by fluorescence in situ hybridisation (FISH) in a 47,XYY male previously studied by sperm karyotyping. A total of 20,021 sperm were studied: 10,017 by two-colour FISH for chromosomes 13 and 21 and 10,002 by three-colour FISH for the sex chromosomes using chromosome 1 as an autosomal control for diploidy and lack of hybridisation. Results were compared with more than 500,000 sperm from 18 normal men. The frequencies of X-bearing (49.4%) and Y-bearing sperm (49.8%) were not significantly different from 50% as shown in our sperm karyotyping study. There was no significant increase in the frequency of diploid sperm compared with control donors. There was a significant increase in the frequency of disomy for chromosome 13 (p < 0.0001) and XY disomy (p = 0.0008) compared with control donors. However, since the frequency of disomy was 0.40% for chromosome 13 and 0.55% for XY disomy, it is not surprising that these increases were not discovered previously in our analysis of 75 sperm karyotypes. Our results suggest that the extra Y chromosome is eliminated during spermatogenesis in the majority of cells but that there may be a small but significant increase in the frequency of aneuploid sperm in these men.     

Individual variation in the frequency of sperm aneuploidy in humans

To examine interindividual differences in sperm chromosome aneuploidy, repeated semen specimens were obtained from a group of ten healthy men, aged 20-21 at the start of the study, and analyzed by multi-color fluorescence in situ hybridization (FISH) analysis to determine the frequencies of sperm aneuploidy for chromosomes X, Y, 8, 18 and 21 and of diploidy. Semen samples were obtained three times over a five-year period. Statistical analysis examining the stability of sperm aneuploidy over time by type and chromosome identified two men who consistently exhibited elevated frequencies of sperm aneuploidy (stable variants): one with elevated disomy 18 and one with elevated MII diploidy. Differences among frequencies of aneuploidy by chromosome were also seen. Overall, disomy frequencies were lower for chromosome X, 8 and 18 than for chromosomes 21 or Y and for XY aneuploidy. The frequency of chromosome Y disomy did not differ from XY sperm frequency. Also, the frequency of meiosis I (XY) and II (YY + XX) sex chromosome errors did not differ in haploid sperm, but the frequency of MII errors was lower than MI errors in diploid sperm. Frequencies of sperm aneuploidy were similar between the first sampling period and the second, two years later. However, the frequency of some types of aneuploidy (XY, disomy Y, disomy 8, total autosomal disomies, total diploidy, and subcategories of diploidy) increased significantly between the first sampling period and the last, five years later, while others remained unchanged (disomy X, 21 and 18). These findings confirm inter-chromosome differences in the frequencies of disomy and suggest that some apparently healthy men exhibit consistently elevated frequencies of specific sperm aneuplodies. Furthermore, time/age-related changes in sperm aneuploidy may be detected over as short a period as five years in a repeated-measures study.     

Chromosome abnormalities in sperm from infertile men with normal somatic karyotypes: oligozoospermia

Recently, intracytoplasmic sperm injection (ICSI) has been extremely successful for the treatment of male infertility. However, transmission of cytogenetic defects to offspring is a great concern. There are two types of cytogenetic problems in patients seeking ICSI; one is the transmission of genetic defects from patients with constitutional chromosomal abnormalities and the second is the generation of de novo defects in infertile men. Generally about 5.1% of infertile men have chromosomal abnormalities. Among such infertile men, men with severe spermatogenesis defects, including oligozoospermia and azoospermia, are subjects for ICSI. Therefore it is very important to obtain cytogenetic information in these infertile patients. Furthermore, oligozoospermic men with a normal somatic karyotype also have increased frequencies of sperm chromosome abnormalities. Oligozoospermia is usually associated with other sperm alterations, for example oligoasthenozoospermia, oligoteratozoospemia and oligoasthenoteratozoospermia. In this review, the relationship between sperm concentration and sperm aneuploidy frequencies has been analyzed. The inverse correlation between the frequency of sperm aneuploidy and concentration has been reported in extensive studies. Especially in severe oligozoospermia, a significantly higher frequency of sex chromosome aneuploidy has been observed and this has been corroborated in recent clinical outcome data of ICSI.     

The relationship between paternal age, sex ratios, and aneuploidy frequencies in human sperm, as assessed by multicolor FISH.

We studied the frequencies of X- and Y-chromosome-bearing sperm, diploidy and disomy for chromosomes 1, 12, X, and Y in sperm from 10 normal men aged 21-52 years, to determine whether there was any relationship between donor age and any of these variables. Multicolor FISH was used to control for lack of probe hybridization and to distinguish diploid sperm from disomic sperm. A minimum of 10,000 sperm per donor was evaluated for each chromosome, for a total of 225,846 sperm studied. Sperm were considered disomic if two fluorescent signals were separated by a minimal distance of one signal domain. The mean frequencies of X- and Y-bearing sperm were 50.1% and 49.0%, respectively; not significantly different from 50%. There was no correlation between paternal age and "sex ratio" in sperm. Similarly, there was no association between the frequency of diploid sperm (mean, .16%; range, .06-.42%) and donor age. For disomy frequencies, there was no relationship between donor age and disomy 12 (mean, .16%; range, .10%-.25%), XX (mean, .07%; range, .03%-.17%), and XY sperm (mean, .16%; range, .08%-.24%). There was a significant increase in the frequency of YY sperm (P = .04; mean, .18%; range, .10%-.43%) and disomy 1 sperm (P = .01; mean, .11%; range, .05%-.18%) with donor age. In summary, our results do not support a correlation between paternal age and sex ratio or diploidy.     

精子端粒长度与特发性男性不育相关

端粒是真核生物染色体末端的多功能特异性DNA-蛋白结构,覆盖在染色体末端,保护基因组的稳定性。端粒在减数分裂过程中起到了十分重要的作用,协助染色体配对、联会、同源重组和分离。精子中的端粒可能在精子的受精能力和胚胎发育中起到重要作用。近年来,端粒与生殖的相关性研究成为一个新的热点,但精子端粒与男性不育间的相关性并不明确。本文采用实时荧光定量PCR方法检测中国特发性男性不育人群(126例)和正常可育男性人群(138例)的精子相对端粒长度,结果发现,特发性男性不育病例的精子平均相对端粒长度(2.894±0.115)低于正常对照组(4.016±0.603),差异具有统计学意义(P=5.097×10^-5);并且精子相对端粒长度与精子密度、精子总数和精子活力都有显著的相关性：精子数量较多和/或精子活力较高,精子相对端粒长度较长。研究结果提示,在中国人群中,精子端粒长度与特发性男性不育具有相关性,精子的端粒长度可能影响精子发生和精子的功能,精子端粒的缩短导致精子数目及活力的降低从而导致男性不育。     

Assessment of autosome and gonosome disomy in human sperm nuclei by chromosome painting

Disomy and diploidy frequencies for autosomes 1–22 and the gonosomes were assessed in 299,442 sperm nuclei from four normal fertile men by chromosome painting. This novel approach allowed us to perform a specific and sensitive detection of each chromosome. A minimum of 5000 sperm nuclei per subject were evaluated for each chromosome by dual colour fluorescence in situ hybridization. The disomy rate proved to be similar for all the autosomes (0.24%) and the diploidy rate varied from 0.12% to 0.15%. No interchromosomal or interindividual differences in the frequency of disomic and diploid sperm nuclei were observed between the four subjects. The mean frequency of XX-, YY- and XY-bearing spermatozoa was estimated to 0.17%, 0.17% and 0.32%, respectively. This strategy constitutes a new approach for detecting aneuploidy in human sperm nuclei and suggests an equal repartition of non-disjunction among chromosomes in male gametes. Received: 7 October 1997 / Accepted: 13 January 1998     

Sperm-FISH analysis and human monitoring: a study on workers occupationally exposed to styrene

Occupational exposure to styrene, a chemical extensively used worldwide, is under investigation for possible detrimental effects on human health, including male reproductive capacity. Aneuploidy in germ cells is the main cause of infertility, abortions and congenital diseases. Fluorescence in situ hybridisation (FISH), is the most efficient cytogenetic molecular technique to date to analyse numerical alterations of chromosomes in spermatozoa. We investigated the frequencies of aneuploidy and diploidy in individuals occupationally exposed to styrene and in healthy unexposed controls. We performed multicolour FISH, using DNA probes specific for the centromeric regions of sex chromosomes and chromosome 2, in decondensed sperm nuclei of samples with normal semen parameters for a total of 18 styrene-exposed subjects and 13 unexposed controls of the same age range. Exposed individuals had worked for at least 2 years during the last 5 years, and continuously for 6 months, in factories producing reinforced plastics. The incidence of aneuploidy and diploidy for the tested chromosomes did not show a statistically significant difference between workers and controls. The exposure to styrene was associated with increased frequencies of nullisomy for sex chromosomes in the group of non-smokers, although only a limited number of subjects belonged to this sub-group. Considering the whole study population, age was associated with an increased frequency of XX disomy, whereas smoking was associated with meiosis II non-disjunction of sex chromosomes. Overall, confounding factors appeared to exert a more important effect than exposure to styrene on numerical chromosome alterations in sperm nuclei of subjects selected for normal semen parameters.     

Spontaneous frequencies of aneuploid and diploid sperm in 10 normal Chinese men: assessed by multicolor fluorescence in situ hybridization

Many studies have been published establishing the background frequencies of disomic and diploid sperm in normal men by fluorescence in situ hybridization (FISH) analysis, with highly significant variance among the reports. Besides interdonor heterogeneity and differences in the experimental protocols used, the question of inherent differences in chromosome malsegregation and meiotic arrest among different geographic and ethnic groups of donors has been raised. In this study, multicolor FISH analysis was carried out on semen samples from 10 nonsmoking, nondrinking Chinese men from the People's Republic of China. The results were compared to FISH data on 10 nonsmoking, nondrinking Canadians under the same experimental conditions, in the same laboratory. A total of 200,497 sperm was scored in the Chinese donors and compared to 202,320 sperm from Canadian donors. Approximately 10,000 sperm per chromosome probe per donor were analyzed. The mean hybridization efficiency was 99.99%. The frequencies of X-bearing and Y-bearing sperm were not significantly different from the expected 50% for each individual and for the combined data from all donors (49.73% vs. 49.46%, P = 0.3946). The mean disomy frequencies (range) were 0.07% (0.02%-0.12%) for chromosome 13, 0.18% (0.09%-0.19%) for chromosome 21, 0.05% (0. 01%-0.09%) for 24,XX, 0.02% (0.01%-0.06%) for 24,YY, and 0.29% (0. 13%-0.49%) for 24,XY. The mean diploidy frequency (range) was 0.38% (0.22%-0.73%) for 13-21 hybridizations and 0.32% (0.07%-0.70%) for XY hybridizations. Highly significant interdonor heterogeneity was found for diploidy (P = 0.0000) and for XY disomy (P = 0.0011), but no age effect was observed in any category of disomic or diploid sperm. The data reported here show no marked differences in disomy and diploidy frequencies between the mainland Chinese and Canadian groups, if donor heterogeneity is taken into account.     

Is there a relationship between sperm chromosome abnormalities and sperm morphology?

This review explores the relationship between sperm chromosomal constitution and morphology. With the advent of techniques for obtaining information on the chromosome complements of spermatozoa, this relationship has been studied in fertile men and in men with a high frequency of chromosomal abnormalities. Using human sperm karyotype analysis, no relationship between sperm chromosome abnormalities and morphology was found in fertile men, translocation carriers or post-radiotherapy cancer patients. Fluorescence in situ hybridization (FISH) analysis has not generally revealed a specific association between morphologically abnormal sperm and sperm chromosome abnormalities, but has indicated that teratozoospermia, like other forms of abnormal semen profiles (aesthenozoospermia, oligozoospermia) is associated with a modest increase in the frequency of sperm chromosome abnormalities. However, FISH studies on some infertile men and mouse strains have suggested that certain types of morphologically abnormal spermatozoa, such as macrocephalic multitailed spermatozoa, are associated with a very significantly increased frequency of aneuploidy. Thus, there may be an association between sperm morphology and aneuploidy in infertile men with specific abnormalities.