XYY spermatogenesis in XO/XY/XYY mosaic mice

The relative frequencies of XYY and XY cells in XO/XY/XYY mosaic mice were compared between somatic cells (bone marrow) and spermatogonia, and between spermatogonia and pachytene or MI spermatocytes. The results indicated there was no selection either for or against XYY spermatogonia. There was, however, a strong selection against XYY spermatocytes during pachytene, with their almost total elimination by the first meiotic metaphase. At pachytene, most XYY cells had trivalent or X univalent/YY bivalent configurations. These findings are contrasted with previous studies of XYY spermatogenesis in mice and are discussed with respect to a model that invokes sex-chromosome univalence as the cause of XYY spermatogenic failure.     

Sex chromosome configurations in pachytene spermatocytes of an XYY mouse

Karyotypic investigation of a phenotypically normal but sterile male mouse showed the presence of an XYY sex chromosome constitution. The synaptic behaviour of the three sex chromosomes was examined in 65 pachytene cells. The sex chromosomes formed a variety of synaptic configurations: an XYY trivalent (40%); an XY bivalent and Y univalent (38.5%); an X univalent and YY bivalent (13.8%); or X, Y, Y univalence (7.7%). There was considerable variation in the extent of synapsis and some of the associations clearly involved nonhomologous pairing. These observations have been compared with previously published information on chromosome configurations at metaphase I from other XYY males.     

An analysis of meiotic impairment and of sex chromosome associations throughout meiosis in XYY mice

The existing XYY meiotic data for mice present a very heterogeneous picture with respect to the relative frequencies of different sex chromosome associations, both at pachytene and diakinesis/metaphase I. Furthermore, where both pachytene and diakinesis/MI data are available for the same males, the frequencies of the different configurations at the two stages are very different. In the present paper we utilise "XYY" and "XY/XYY" mosaic mice with cytologically distinguishable Y chromosomes to investigate the factors responsible for this heterogeneity between different males and between the two meiotic stages. It is concluded (1) that the initial pattern of synapsis is driven by the relatedness of the three pseudoautosomal regions (PARs); (2) that the order and extent of PAR synapsis within radial trivalents are also affected by PAR relatedness and that this leads to chiasmata being preferentially formed between closely related PARs; (3) that trivalents with a single chiasma resolve into a bivalent + univalent by the diakinesis stage; (4) that although many spermatocytes with asynapsed sex chromosomes are eliminated between pachytene and diakinesis, those that survive this phase of elimination progress to the first meiotic metaphase (MI) and accumulate in large numbers, leading to an over-representation of those with univalents as compared to radial trivalents; and (5) that the arrested MI cells are eventually eliminated, so that very few "XYY" cells contribute products to MII.     

Recombination in the pseudoautosomal region in a 47,XYY male

Males with a 47,XYY karyotype generally have chromosomally normal children, despite the high theoretical risk of aneuploidy. Studies of sperm karyotypes or FISH analysis of sperm have demonstrated that the majority of sperm are chromosomally normal in 47,XYY men. There have been a number of meiotic studies of XYY males attempting to determine whether the additional Y chromosome is eliminated during spermatogenesis, with conflicting results regarding the pairing of the sex chromosomes and the presence of an additional Y. We analyzed recombination in the pseudoautosomal region of the XY bivalent to determine whether this is perturbed in a 47,XYY male. A recombination frequency similar to normal 46,XY men would indicate normal pairing within the XY bivalent, whereas a significantly altered frequency would suggest other types of pairing such as a YY bivalent or an XYY trivalent. Two DNA markers, STS/STS pseudogene and DXYS15, were typed in sperm from a heterozygous 47,XYY male. Individual sperm (23,X or Y) were isolated into PCR tubes using a FACStarPlus flow cytometer. Hemi-nested PCR analysis of the two DNA markers was performed to determine the frequency of recombination. A total of 108 sperm was typed with a 38% recombination frequency between the two DNA markers. This is very similar to the frequency of 38.3% that we have observed in 329 sperm from a normal 46,XY male. Thus our results suggest that XY pairing and recombination occur normally in this 47,XYY male. This could occur by the production of an XY bivalent and Y univalent (which is then lost in most cells) or by loss of the additional Y chromosome in some primitive germ cells or spermatogonia and a proliferative advantage of the normal XY cells.     

A 39,X/40,XY/41,XYY mosaic male mouse

Cytogenetic analyses of bone marrow and gonadal cells in a male mouse, which appeared to be normal, revealed mosaicism in both tissues. Three chromosome complements, 39,X, 40,XY, and 41,XYY, were found in both bone marrow and spermatogonia, while only the last two complements were found in spermatocytes. In this mouse, unlike in the human, the XYY cells showed a proliferative advantage over the XY cells. In XYY cells at diakinesis/metaphase I the gonosomes showed all possible types of association, and a pairing advantage of the X chromosome was clearly demonstrated. The fertility of the mouse was not determined. However, since the epididymal sperm count was reduced by only 55% and the incidence of sperm head abnormality was near normal, it is not evident that the mouse was sterile.     

Synaptonemal complex analysis in human male infertility

The fine structural features of human spermatocytes from carriers of some of the most frequent chromosomal abnormalities are reviewed on the basis of original data and previous reports from the literature. Special emphasis is given to the Robert-sonian translocations t (13; 14), to one specific reciprocal translocation involving chromosome 21, and to Y disomy in spermatocytes from XYY men. Synaptonemal complex analysis shows that in many carriers of chromosomal aberrations that lead to pachytene configurations having terminal asynaptic segments in autosomes, there is a gradual association of these asynaptic segments with the XY body. This associations with the XY pair is assumed to trigger a process of germ cell deterioration, presumably through the spreading of the X-chromosome inactivation towards autosomal segments. Another different process of germ cell deterioration occurs when the X chromosome becomes an univalent, as in XYY men with persistence of two Y chromosomes in the germ line. The renewed interest in the examination of spermatocytes from human testicular biopsies is commented upon.     

Spontaneous occurrence of XYY primary spermatocytes in the Sitka deer mouse

Analysis of microspread, silver-stained primary spermatocytes from chromosomally and phenotypically normal Peromyscus sitkensis revealed the occurrence of XYY zygotene and pachytene nuclei at low frequency in three of eight individuals examined. Observed pairing configurations of sex chromosomes included a trivalent and a Y bivalent-X univalent. The data suggest that premeiotic nondisjunction may be involved in the origination of XYY chromosomal conditions.     

Meiotic behaviour of sex chromosomes investigated by three-colour FISH on 35 142 sperm nuclei from two 47,XYY males

Meiotic segregation of sex chromosomes from two fertile 47,XYY men was analysed by a three-colour fluorescence in situ hybridisation procedure. This method allows the identification of hyperhaploidies (spermatozoa with 24 chromosomes) and diploidies (spermatozoa with 46 chromosomes), and their meiotic origin (meiosis I or II). Alpha-satellite probes specific for chromosomes X, Y and 1 were observed simultaneously in 35 142 sperm nuclei. For both 47,XYY men (24 315 sperm nuclei analysed from one male and 10 827 from the other one) the sex ratio differs from the expected 1:1 ratio (P < 0.001). The rates of disomic Y, diploid YY and diploid XY spermatozoa were increased for both 47,XYY men compared with control sperm (142 050 sperm nuclei analysed from five control men), whereas the rates of hyperhaploidy XY, disomy X and disomy 1 were not significantly different from those of control sperm. These results support the hypothesis that the extra Y chromosome is lost before meiosis with a proliferative advantage of the resulting 46,XY germ cells. Our observations also suggest that a few primary spermatocytes with two Y chromosomes are able to progress through meiosis and to produce Y-bearing sperm cells. A theoretical pairing of the three gonosomes in primary spermatocytes with an extra sex chromosome, compatible with active spermatogenesis, is proposed. Received: 12 April 1996 / Revised: 26 August 1996     

Increased incidence of disomic sperm nuclei in a 47,XYY male assessed by fluorescent in situ hybridization (FISH)

Using triple-colour fluorescent in situ hybridization in decondensed sperm heads, we assessed the sex-chromosome distribution in spermatozoa from a 47,XYY male compared with controls. The incidence of spermatozoa with 24,XY (0.30%) and 24,YY (1.01%) disomy was significantly higher than in our control series. Diploid meiocytes present in the ejaculate were mainly 47,XYY (60.6–86.7%), and haploid meiocytes were mainly 24,XY (78.1%).These results suggest that, although the extra Y chromosome is thought to be eliminated during spermatogenesis, XYY germ cells can complete meiosis and produce disomic spermatozoa. Received: 5 August 1996 / Revised: 2 October 1996     

X/XY/XYY mosaicism as a cause of subfertility in boars: a single case study

Sex chromosome abnormalities are common in mammals and humans and are often associated with subfertility. In this study a boar with normal sperm parameters was indicated to have reduced prolificacy from figures obtained for return rate, farrowing rate and total number of piglets born. G-banded cytogenetic analysis of peripheral blood identified an abnormal mosaic sex chromosome constitution 39,XYY[74]/38,XY[23]/37,X[3]. Cytogenetic analysis of fibroblasts confirmed this mosaic karyotype with similar percentages of cell lines observed 39,XYY[76]/38,XY[19]/37,X[5]. External genitalia revealed a poorly developed scrotum with the right testicle being smaller than the left. To the best of our knowledge this is the first time that this chromosome constitution has been reported in the pig. It is of particular interest that this karyotype is associated with reduced boar fertility, which could lead to potential economic losses if such a boar were selected for breeding purposes.     

Sex-chromosome aberrations in wood lemmings (Myopus schisticolor)

The wood lemming displays certain peculiar features: (1) The sex ratio shows a prevalence of females (FRANK, 1966; KALELA and OKSALA, 1966), and some females produce only female offspring (KALELA and OKSALA, 1966). (2) In a considerable proportion (in the present material, slightly less than half) of the females, an XY chromosome complement is found in the somatic tissues, but the Y is absent in the germ line of those studied (Fredga et al., 1976). Therefore, (3) a mechanism of double nondisjunction in early fetal life of XY females has to be postulated, which replaces the Y in the germ line by duplication of the X. It is assumed (4) that the X of XY females bears a sex-reversal factor that affects the male determining action of the Y (Fredga et al., 1977). There is (5) a strong presumption that in most cases the XY females are those that produce daughters only, but (6) a few exceptions may occur (FRANK, unpublished observations), suggesting that the regulation according to assumption 3 (perhaps also to 4) is incomplete in XY females. In the present report, four females are described with a 31,XO karyotype, two females with 33,XYY or 32,XY/33,XYY, respectively, two males with a 33,XXY, and one male with a 32,XX/33,XXY karyotype, as observed in a consecutive series of 502 wood lemmings. The incidence of sex-chromosome anomalies in liveborn and adult animals was 2.3%; the overall incidence, including embryos, was 1.79%. Neither the somatic XO constitution nor the existence of an extra Y in females precludes fertility. However, the XXY condition in the male results in sterility. There is certain evidence that an instability of the proposed mechanism for double mitotic nondisjunction of the sex chromosomes in oogonia accounts for the high rate of sex-chromosome aberrations in wood lemmings, at least when the mother is XY.     

Incidence of 47,XYY males: Implications of the production of 47,XYY offspring by 47,XYY males

Abstract

Chromosomally normal 46,XY males can have 47,XYY male offspring as a result of fertilization of a normal ovum by a YY spermatozoon, produced by nondisjunction in the second meiotic division or by mitotic nondisjunction of the Y chromosome in early stages of embryonic development of a 46,XY fetus. If such meiotic and mitotic nondisjunctions were random events and if these were the only source of 47,XYY males in the population, the incidence of 47,XYY males would remain constant. Two cases have been reported, however, in which 47,XYY males produced 47,XYY male offspring. If there are 47,XYY males who are a source of 47,XYY males in the population, there is the possibility that the incidence of 47,XYY males is changing. A discrete‐generation model is presented which describes (1) the change in incidence of 47,XYY males from one generation to the next; (2) the incidence at equilibrium; and (3) the incidence as a function of the probability that a 47.XYY male has a 47,XYY offspring, and as a function of the mean number of offspring of 47,XYY males relative to the mean number of offspring of 46,XY males.     

Evidence that sex chromosome asynapsis, rather than excess Y gene dosage, is responsible for the meiotic impairment of XYY mice

There is extensive evidence for the existence of a meiotic checkpoint that acts to eliminate spermatocytes that fail to achieve full sex chromosome synapsis at the pachytene stage of the first meiotic prophase. XYY mice are nearly always sterile, with clear signs of meiotic impairment, and sex chromosome asynapsis has been proposed to underlie this impairment. However, a study of XYY*(X) mice (mice having three sex chromosomes but only a single dose of Y genes) revealed that these mice are fertile, and thus implicated Y gene dosage as a major factor in the sterility of XYY mice. To address this question further, sex chromosome synapsis and spermatogenic proficiency were compared between XYY*(X) and XYY mice generated in the same litters. This established that differences in spermatogenic proficiency within and between the two genotypes correlated with the frequency of radial trivalent formation (full sex chromosome synapsis); XYY*(X) males, as a group, had double the radial trivalent frequency of XYY males. This observation provides strong support for the view that sex chromosome asynapsis (or some consequence thereof), rather than Y gene dosage, is the major factor leading to the meiotic impairment of XYY mice.     

Spermatogenesis in an infertile XYY man

Summary Testicular histology and meiosis has been studied in an XYY male patient identified at an infertility clinic. This man was found to have an XYY sex chromosome complement in 15% of spermatogonial metaphases. There was no clear evidence of 2 Y chromosomes at diakinesis but there appeared to be a slight excess of sperm with a fluorescent Y body.     

Y-chromosome disomy and trisomy in scarabaeid and cerambycid beetles

In a series of about 500 specimens, including 420 males, of karyotyped Polyphaga beetles, 5 males with chromosome Y aneuploidy were detected. One male of each Dicronorrhina derbyana oberthuri (Scarabaeidae), Agapanthia violacea and Morimus funereus (Cerambycidae) were XYY, and 2 probably related and sterile males of Marmylida marginella (Scarabaeidae) were XYYY. These and literature data suggest that Y chromosome aneuploidies are much more frequent in polyphagan beetles than any other group of animals with an XY/XX sex determinism. The origin of this particularity probably lies in the unique mode of sex chromosome association at meiosis I: it is not synaptic but realized through nucleolar proteins forming the well-known parachute-like structure (Xy(p)). This has 2 possible consequences. The first one is the regular association of several sex chromosomes at metaphase I and segregation at anaphase I. It allows, for instance, XYY (Xyy(p)) males to procreate XYY sons. The second consequence is the occasional remain of nucleolar proteins embedding sex chromosomes in spermatocytes II. We propose that it could impede the correct segregation of Y chromatids after centromere split at anaphase II, and contribute to form YY gametes by XY males and YYY gametes by XYY males. The tendency for increasing the number of Ys would not be strongly limited at the XY level, but only at the XYY level by male infertility at higher Y ploidies.     

The 47,XYY male, Y chromosome, and tooth size.

Permanent teeth of 12 individuals with a 47,XYY chromosome constitution have been examined. The tooth sizes of 47,XYY males were found to be larger than those of control males and females. In many instances the differences were statistically significant. Using these results, it was possible to conclude that a factor or factors which influence excess growth of 47,XYY males probably are in effect during prenatal life, but without doubt must be in effect very early in postnatal life. The time period needed for the achievement of final excess growth is relatively short, in the case of first permanent molars probably only from 2 1/2 to 3 1/2 years. On the basis of the finding that the Y chromosome apparently carries genes affecting tooth sizes in normal males [1], it was suggested that gene products of the extra Y chromosome could cause the observed size difference between normal and 47,XYY males. The nature of the influence of one versus two Y chromosomes on growth was discussed in terms of the possible influence of the Y chromosome on the cell divisions within the developing tooth germ.     

Dicentric Y chromosome in a male pseudohermaphrodite 45,X/46,X, dic (Y)/47, XYY]

The mosaicism 45,X/46,XY,terrea(Y,Y)(pterpter)/47,XYY was observed in an 8-month-old child with male pseudohermaphroditism. The presence of a 47,XYY population points to a post-zygotic origin of the rearrangement. The loss of Yp material is in favor of localization of masculinization factor(s) to the proximal segment of Yq. Twenty-two relevant observations reported in the literature previously are discussed.     

Meiosis in a sterile male mouse with an isoYq marker chromosome

A male mouse with a metacentric Y chromosome of twice the normal size has been studied chromosomally in bone marrow mitoses, spermatogonial mitoses, and diakinesis-metaphase I primary spermatocytes. A low frequency of nondisjunction for this chromosome (2%) was noted in both bone marrow and spermatogonial mitoses. In spermatogonial mitoses, loss of the Y chromosome had occurred to the extent that 12% of spermatogonia were XO, resulting in 17% XO primary spermatocytes. Hardly any stages beyond the primary spermatocyte stage were encountered, which agrees with testis weights of approximately 30% of normal. Surface-spread pachytene spermatocytes yielded few cells that were analyzable for their total complement of synaptonemal complexes. The Y chromosome showed complete fold-back pairing and was located far away from the X chromosome. X and Y chromosomes were paired in 14.5% of the diakinesis-MI spermatocytes that contained a Y chromosome. The origin of this chromosome is discussed against the background of localization of the gene for the testis-determining factor on the short arm of the mouse Y chromosome.     

The mouse Y* chromosome involves a complex rearrangement, including interstitial positioning of the pseudoautosomal region.

Cytological analysis of the mouse Y* chromosome revealed a complex rearrangement involving acquisition of a functional centromere and centromeric heterochromatin and attachment of this chromosomal segment to the distal end of a normal Y* chromosome. This rearrangement positioned the Y* short-arm region at the distal end of the Y* chromosome and the pseudoautosomal region interstitially, just distal to the newly acquired centromere. In addition, the majority of the pseudoautosomal region was inverted. Recombination between the X and the Y* chromosomes generates two new sex chromosomes: (1) a large chromosome comprised of the X chromosome attached at its distal end to all of the Y* chromosome but missing the centromeric region (XY*) and (2) a small chromosome containing the centromeric portion of the Y* chromosome attached to G-band-negative material from the X chromosome (YX). Mice that inherit the XY* chromosome develop as sterile males, whereas mice that inherit the Y*X chromosome develop as fertile females. Recovery of equal numbers of recombinant and nonrecombinant offspring from XY* males supports the hypothesis that recombination between the mammalian X and Y chromosomes is necessary for primary spermatocytes to successfully complete spermatogenesis and form functional sperm.     

Chromosome studies in the red howler monkey, Alouatta seniculus stramineus (Platyrrhini, Primates): description of an X1X2Y1Y2/X1X1X2X2 sex-chromosome system and karyological comparisons with other subspecies

In the red howler monkey, Alouatta seniculus stramineus (2n = 47, 48, or 49), variations in diploid chromosome number are due to different numbers of microchromosomes. Males exhibit a Y;autosome translocation involving the short arm of an individual biarmed autosome. Consequently, the sex-chromosome constitution in the male is X1X2Y1Y2, with X1 representing the original X chromosome, X2 the biarmed autosome (No. 7), Y1 the Y;7p translocation product, and Y2 the acrocentric homolog of 7q. In the first meiotic division, a quadrivalent with a chain configuration can be observed in spermatocytes. Females have an X1X1X2X2 sex-chromosome constitution. Chromosome heteromorphisms were observed in pair 13, due to a pericentric inversion, and pair 19, due to the presence of constitutive heterochromatin. Microchromosomes, which varied in number between individuals, were also heterochromatic. NOR-staining was observed at two separate sites on a single chromosome pair (No. 10). A comparison of A.s. stramineus with A.s. macconnelli shows that these two subspecies have identical diploid chromosome numbers (47, 48, or 49), again due to a varying number of microchromosomes, and that they share a similar sex-chromosome constitution. Their karyotypes, however, are not identical, but can be derived from each other by a reciprocal translocation. Further comparisons with other A. seniculus subspecies reported in the literature indicate that this taxon is not karyologically uniform and that substantial chromosome shuffling has occurred between populations that have been considered to be subspecies by taxonomic criteria based on their morphometric attributes.