Biomedical subjects

R M Speed

Publications and source records attributed to R M Speed.

At least 37 records · Page 2Linked to original sources

PubMed1989

Deleted Yq in the sterile son of a man with a satellited Y chromosome (Yqs).

Disturbed spermatogenesis and azoospermia are reported in a man with a deleted Y chromosome. The anomalous Y chromosome appears in the karyotype as a small metacentric marker. In situ hybridisation using three different Y specific DNA probes shows that deletion at Yq11 has resulted in loss of all distal heterochromatin. The sterility of the patient indicates loss also of the azoospermia factor (AZF) located at the Yq distal euchromatic/heterochromatic interface. Microspread and air dried meiotic preparations show a severe impairment of spermatogenesis but rare cells are seen to be progressing to the late prophase stage. The testicular histology shows most of the seminiferous tubules to be completely hyalinised. The father and a fertile brother of the proband show a satellited Y chromosome (Yqs) in their karyotypes. The case appears to be the first of its kind reported in which a father with a satellited Y chromosome has produced a son carrying a different Y chromosome anomaly. The possible derivation of the one from the other is discussed.

Adult↗

PubMed1988

The possible role of meiotic pairing anomalies in the atresia of human fetal oocytes.

Following a previous study of human fetal oocytes analysed by light and electron microscope microspreading (Speed 1985), a further and more extensive analysis has now been carried out at electron microscope (EM) level. Some new anomalies not previously observed are described. More than one-third of all pachytene oocytes show degeneration (Z-cells) or synaptic errors which might lead to germ cell death. Meiotic pairing anomalies appear to be much more common among oocytes than spermatocytes, and could be significant factor in the high rate of atresia found between mid-term and birth in the human ovary.

Female↗

PubMed1988

Chromosomal organization of the cytochrome P450-2C gene family in the mouse: a locus associated with constitutive aryl hydrocarbon hydroxylase.

Cytochromes P-450 represent a superfamily of enzymes with a central role in the metabolism of drugs, chemical toxins, and carcinogens. We have used genetic analysis to establish the complexity and catalytic function of a recently identified constitutively expressed murine hepatic cytochrome P-450 encoded by P450-2C. Southern blotting analysis shows that there are at least seven or eight genes within this family in the mouse and rat and that DNA restriction fragment length variants between different mouse inbred strains are observed. Analysis of recombinant inbred strains derived from these parent strains shows (i) these genes are clustered within 1 centimorgan, (ii) this gene family does not correspond to any of the known cytochrome P-450 loci or map near any well-characterized genomic markers, and (iii) this gene family segregates to within 1-2 centimorgans of a locus controlling constitutive aryl hydrocarbon hydroxylase activity in mice. With use of Chinese hamster/mouse somatic cell hybrids, the P450-2C locus was assigned to a region of mouse chromosome 19 that appears to be syntenic with the previously mapped human P450C2C locus on human chromosome 10. By in situ hybridization to mitotic mouse chromosomes, we have localized this region to the tip of chromosome 19. These results are discussed in relation to the physiological roles of this P-450 family in foreign compound metabolism and steroid oxidations.

Animals↗

PubMed1988

A fertile mule and hinny in China.

Anecdotal reports of fertility in female mules (jack donkey x mare) and hinnies (stallion x jenny donkey) have appeared in the literature over the years, but scientists have generally regarded them with scepticism. The fact that some of these hybrids can come into estrous and ovulate makes fertility conceivable, given that opportunity for mating arises. In China, where mules are bred extensively for work on the farms, a fertile female mule and a fertile female hinny have now been verified by chromosomal investigation. Each had mated with a donkey and produced a filly foal. The foals show unique hybrid karyotypes different from the mule's or hinny's and different from each other's. The studies make it clear that mule and hinny fertility, at least for the female hybrid, is a real possibility.

Animals↗

PubMed1988

Meiotic analysis of two human reciprocal X-autosome translocations.

Two cases of human reciprocal X-autosome translocation, t(X;12) and t(X;2), are described in sterile males, along with meiotic findings. Each carrier had inherited the translocation from his mother. Both showed azoospermia and germ-cell maturation arrest at the primary spermatocyte level, with most cells being arrested at the pachytene stage. A few metaphase I (MI) divisions were found, with occasional metaphase II cells being seen in the t(X;2) carrier. MI air-dried preparations gave clear evidence of chain quadrivalent formation. In the t(X;2) heterozygote, the pairing characteristics of the quadrivalent at pachytene were also analyzed in electron microscopic spreads. Disturbance of pairing around the breakpoints characterized most quadrivalents, and there was evidence in about 20% of the cells that nonhomologous pairing had taken place between the translocated chromosomes and the normal chromosome 2. Comparisons are made with similar nonhomologous pairing configurations seen at pachytene in quadrivalents of male reciprocal X-autosome translocations of the mouse.

Adult↗

PubMed1987

Cytological evidence that the Sxr fragment of XY,Sxr mice pairs homologously at meiotic prophase with the proximal testis-determining region.

Self-pairing of the Y chromosome at prophase of meiosis in XY,Sxr male mice appears to take place in many cells to the exclusion of pairing between the Y and the X. This phenomenon offers an explanation for the high level of X-Y separation seen in these males at prophase of meiosis, additional separations being evident, however, when metaphase I (MI) cells are examined. A minority of prophase cells show the Y paired both autologously and with a sub-terminal region of the X which could be the normal pairing region. The balloon-like configurations observed when self-pairing occurs suggest that the distal Sxr fragment is inverted on the Y chromosome of Sxr carrier males in relation to the normal proximal testis-determining (Td)-containing region.

Animals↗

PubMed1987

Immunocytochemical labelling of the kinetochore of human synaptonemal complexes, and the extent of pairing of the X and Y chromosomes.

An immunocytochemical method was used to label the kinetochores on human synaptonemal complexes. Synaptonemal complex spreads were labelled with autoimmune CREST serum, followed by a second antibody labelled with colloidal gold, and examined by electron microscopy. Clusters of gold particles were found at discrete sites which were identified as kinetochores on the autosomal synaptonemal complexes, as well as on the XY pair. This method was used to investigate the extent of pairing of the human X and Y chromosomes at pachytene. Our observations confirm earlier work, based purely on measurements, that the pairing of the sex chromosomes sometimes extends beyond the centromere of the Y chromosome into the long arm. At the same time we showed that the centromeric indices of the X and Y at pachytene are highly variable, so that measurements alone are not sufficient to estimate the degree of pairing of the sex chromosomes.

Centromere↗

PubMed1987

Ring XY bivalent: a new phenomenon at metaphase I of meiosis in man.

The unusual appearance of a ring XY bivalent at metaphase I of meiosis is reported in some cells of an oligospermic human male. Higher than usual frequencies of ring configuration in the XY pair were also observed during prophase I. The defect could be attributable to loss of some DNA sequences from the distal heterochromatic tip of the Y chromosome long arm.

Adult↗

PubMed1987

Pericentric inversion in human chromosome 1 and the risk for male sterility.

A pericentric inversion in chromosome 1 of a severely oligospermic human male is reported. Pachytene analysis in microspread preparations shows an absence of full loop formation in the inversion bivalent and only the rare occurrence of a partial loop. The majority of cells exhibit extensive asynapsis across the inverted segment, or a normal looking synaptonemal complex indicative of heterologous pairing along the length of the inversion. Crossing over is reduced in the No 1 bivalent with only a rare chiasma being seen in the inverted region at metaphase I. Males heterozygous for a pericentric inversion in chromosome 1 appear to be at severe risk for infertility brought about by spermatogenic disturbance. The dearth of full loops at prophase in this patient, and in other pericentric inversion cases studied both in man and other species, raises the question of whether recombinant offspring might be rarer than anticipated on a theoretical basis owing to asynapsis or early heterologous synapsis across inverted segments.

Adult↗

PubMed1986

Oocyte development in XO foetuses of man and mouse: the possible role of heterologous X-chromosome pairing in germ cell survival.

The pairing characteristics of the X axis in XO human and mouse oocytes were studied by the spreading technique throughout meiotic prophase. In three human XO foetuses, germ cell development was seen to be largely blocked at the preleptotene stage. In XO mice on the other hand, oocytes surviving through pachytene increasingly show the X axis making a non-homologous association with itself or with an autosome. Such associations take the form hairpins or rings when self pairing occurs or triradial structures when involvement is with an autosome. Pairing initiation in the autosomes involved is disturbed by the X axis suggesting that the heterologous pairing seen is taking place at the earliest stage of synaptonemal complex formation, namely zygotene. It is suggested, that in the XO mouse, and perhaps also in rare fertile XO humans, survival, of a population of oocytes into the adult is ensured by the ability of the X axis to pair non-homologously at meiotic prophase, thus satisfying pairing requirements.

Animals↗

PubMed1986

Prophase pairing in a mosaic 18p-;iso 18q human female foetus studied by surface spreading.

The pachytene configurations formed in the ovary of a mosaic 18p-;iso 18q human foetus (22 weeks gestation) are analysed using a surface spreading technique. Three features of interest are the apparent meiotic delay of oocyte development, oocyte degeneration, and the triple pairing which occurs in one cell line when the iso 18q both pairs with itself and with the normal chromosome 18.

Cell Line↗

PubMed1986

Abnormal RNA synthesis in sex vesicles of tertiary trisomic male mice.

The XY bivalent contained within the sex vesicle of chromosomally normal male mice shows virtually no RNA transcriptional activity as measured by autoradiography during the prophase of meiosis. Tertiary trisomic males, derived from the T 70 H and T 31 H reciprocal translocations, include the extra small marker chromosome to varying degrees within the sex vesicle. It has been found that RNA transcription occurs within the sex vesicles of such trisomics. An attempt has been made to correlate such activity either to the extra marker chromosome itself or to a possible reactivation of the normally quiescent sex bivalent. The relationship of the abnormal RNA synthesis to the breakdown of meiosis in tertiary trisomics and to their subsequent reduced fertility is discussed.

Animals↗

PubMed1986

A human 9;20 reciprocal translocation associated with male infertility analyzed at prophase and metaphase I of meiosis.

Details are given of a meiotic prophase analysis, carried out by spreading, of a human 9;20 reciprocal translocation ascertained in a subfertile, oligospermic male. Air-dried meiotic preparations revealed the presence of translocation quadrivalents at metaphase I. Germ-cell degeneration was evident from the early prophase of meiosis onward. Associations between the translocation quadrivalent and XY bivalent at pachytene were seen in only 20% of the cells and seemed not to be the prime cause of germ-cell failure. Pairing disruption around the breakpoints of the translocation at pachytene and/or pairing failure in one arm of the pachytene cross was observed in a total of 87% of all cells analyzed. This could have contributed significantly to germ-cell atresia.

Cells, Cultured↗

PubMed1985

The prophase stages in human foetal oocytes studied by light and electron microscopy.

The progression of the prophase stages of meiosis in human foetal ovaries is reported from a series of aborted foetuses spanning the first two trimesters of gestation. A surface-spreading technique allowed cells to be examined at both light and electron microscope levels. The pachytene stage was specifically examined for evidence of synaptic or other abnormalities. Two observations of interest are the relatively high incidence with which errors of pairing occur and second the state of thickening observed when such unpaired axes are stained with silver.

Cells, Cultured↗

PubMed1984

Meiotic configurations in female trisomy 21 foetuses.

Analysis of the meiotic configurations formed by the three No 21 chromosomes in oocytes from two trisomy 21 foetuses was undertaken using a spreading technique. Light microscope analysis of the first gave limited resolving power, such that over half the oocytes could not be classified as to presence or absence of trivalent or bivalent plus univalent. In the second, investigated at the electron microscope level, all 65 cells analysed were informative and precise detail of meiotic pairing in trivalents could be obtained. Two principal forms of trivalent occurred, one in which pairing was initiated at opposite ends of the three No 21's, each initiation point involving only two of the three homologous lateral elements; the other in which pairing was initiated by all three elements at the same end, a triple synaptonemal complex being formed. Only in one oocyte out of the 65 analysed at EM level, however, did triple pairing occur along the entire length of the No 21 trivalent. All others showed splitting into bivalent and univalent at some point along the structure. Unpaired regions within trivalents and all univalents were consistently seen to be thickened and dark staining with silver over the whole period from pachytene to diplotene. This contrasted with the desynapsing lateral elements of previously paired synaptonemal complexes which appeared thin by comparison at diplotene. The significance of the thickening remains, as yet, obscure.

Amniocentesis↗

PubMed1984

On the nature and extent of XY pairing at meiotic prophase in man.

Evidence is presented that pairing between the human X and Y chromosomes could be more extensive at early pachytene than has previously been supposed and could involve even the entire euchromatic portion of the Y chromosome. Following desynapsis over the major part of the X and Y axes, a small paired segment of Xp and Yp remains into late pachytene. Association between the distal tips of Xq and Yq can also be observed in about one half of the spermatocytes examined. A hypothesis linking meiotic pairing to early replicating sites along the chromosomes is proposed.

Adult↗

PubMed1984

Morphological and temporal sequence of meiotic prophase development at puberty in the male mouse.

The correct sequence of meiotic prophase development in the male mouse has been established by the use of pubertal males. The first wave of spermatogenesis at this time provides a unique opportunity to study progressive meiotic development in a direct way. Air-dried and micro-spread analyses have been carried out. Temporal and morphological progression at this time is entirely consistent with that occurring in the later waves of meiosis of the adult male. Morphological detail shows delayed pairing of the X and Y chromosomes relative to the autosomes. The longest XY synaptonemal complex is seen in early pachytene cells, occupying up to 72% of the length of the Y and 22% of the length of the X axis. By late pachytene, end-to-end pairing in the XY bivalent is established, the autosomal axes remaining fully paired. Desynapsis of the autosomes commences at early diplotene. A 'diffuse' diplotene stage in the male, comparable to the dictyate stage of the female, could not be found. Marked lengthening of the XY and autosomal axes did, however, occur through the diplotene stage.

Animals↗

PubMed1983

Meiosis in the foetal mouse ovary. II. Oocyte development and age-related aneuploidy. Does a production line exist?

A systematic search for chromosome pairing defects in foetal mouse oocytes has been carried out in two different strains (Swiss and CBA/Ca) over days 15-19 of gestation and on day 1 post-partum. The aim was to seek direct cytological evidence for a "production line" of oocyte development, or the occurrence of pairing anomalies at meiotic prophase that might lead, in the adult female, to nondisjunction at anaphase I. No evidence for either was found. The data argue against the "production line" hypothesis as the basis for maternal age-related increases in aneuploidy in the mouse. Attempts to analyse chiasmata in oocytes at diplotene were unsuccessful.

Aneuploidy↗