Biomedical subjects

Terry Hassold

Publications and source records attributed to Terry Hassold.

6 recordsLinked to original sources

PubMed2006

Synaptic defects at meiosis I and non-obstructive azoospermia.

BACKGROUND: Recent advances in immunofluorescence methodology have made it possible to directly monitor protein localization patterns in germ cells undergoing meiosis. We used this technology to examine the early stages of meiosis in testicular material obtained from men presenting for evaluation at infertility clinics. METHODS: Specifically, we compared meiotic progression, synapsis and recombination in 34 individuals with obstructive azoospermia ('controls') to 26 individuals with non-obstructive azoospermia (NOA) ('cases'). RESULTS: In 9 of the 26 cases, no germ cells were identified, but in the remaining 17, there was at least some progression through meiosis. Most of these individuals appeared to have normal levels of spermatogenic activity, with little evidence of meiotic impairment. However, in three individuals, we observed either complete or partial meiotic arrest associated with abnormalities in synapsis. CONCLUSIONS: This suggests that >10% of cases of unexplained NOA may be attributable to severe meiotic defects. The characterization of these meiotic arrest phenotypes may guide further research into the molecular basis of unexplained infertility.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Meiosis and sex chromosome aneuploidy: how meiotic errors cause aneuploidy; how aneuploidy causes meiotic errors.

As a group, sex chromosome aneuploidies - the 47,XXY, 47,XYY, 47,XXX and 45,X conditions - constitute the most common class of chromosome abnormality in human live-births. Considerable attention has been given to the somatic abnormalities associated with these conditions, but less is known about their meiotic phenotypes; that is, how does sex chromosome imbalance influence the meiotic process. This has become more important with the advent of assisted reproductive technologies, because individuals previously thought to be infertile can now become biological parents. Indeed, there are several recent reports of successful pregnancies involving 47,XXY fathers, and suggestions that cryopreservation of ovarian tissue might impart fertility to at least some Turner syndrome individuals. Thus, the possible consequences of sex chromosome aneuploidy on meiotic chromosome segregation need to be explored.

Aneuploidy↗

PubMed2005

Sex, not genotype, determines recombination levels in mice.

Recombination, the precise physical breakage and rejoining of DNA between homologous chromosomes, plays a central role in mediating the orderly segregation of meiotic chromosomes in most eukaryotes. Despite its importance, the factors that control the number and placement of recombination events within a cell remain poorly defined. The rate of recombination exhibits remarkable species specificity, and, within a species, recombination is affected by the physical size of the chromosome, chromosomal location, proximity to other recombination events (i.e., chiasma interference), and, intriguingly, the sex of the transmitting parent. To distinguish between simple genetic and nongenetic explanations of sex-specific recombination differences in mammals, we compared recombination in meiocytes from XY sex-reversed and XO females with that in meiocytes from XX female and XY male mice. The rate and pattern of recombination in XY and XO oocytes were virtually identical to those in normal XX females, indicating that sex, not genotype, is the primary determinant of meiotic recombination patterns in mammals.

Animals↗

PubMed2004

Meiosis I arrest and azoospermia in an infertile male explained by failure of formation of a component of the synaptonemal complex.

OBJECTIVE: To characterize the early stages of meiosis in a male with unexplained azoospermia. DESIGN: Case report. SETTING: Case Western Reserve University and University Hospitals of Cleveland. PATIENT(S): A 30-year-old male with nonobstructive azoospermia. INTERVENTION(S): Immunostaining for components of the synaptonemal complex and recombination-associated proteins, fluorescence in situ hybridization (FISH) for specific chromosomes. MAIN OUTCOME MEASURE(S): Progression to and through pachytene of meiosis I in controls and in the patient. RESULT(S): We observed complete meiosis I arrest in the patient, associated with failure of formation of the mature, tripartite synaptonemal complex. CONCLUSION(S): Abnormalities in synaptonemal complex formation are responsible for a proportion of cases of unexplained male infertility.

Adult↗

PubMed2004

Variation in human meiotic recombination.

As recently as 20 years ago, there was relatively little information about the number and distribution of recombinational events in human meiosis, and we knew virtually nothing about factors affecting patterns of recombination. However, the generation of a variety of linkage-based genetic mapping tools and, more recently, cytological approaches that enable us to directly visualize the recombinational process in meiocytes, have led to an increased understanding of human meiosis. In this review, we discuss the different approaches used to study meiotic recombination in humans, our understanding of factors that affect the number and location of recombinational events, and clinical consequences of variation in the recombinational process.

Age Factors↗

PubMedDate not supplied

Klinefelter syndrome: expanding the phenotype and identifying new research directions.

PURPOSE: The purpose of this study is to summarize new data on etiology and clinical features of Klinefelter syndrome in order to derive research priorities. METHODS: This study was conducted using critical reviews of selective topics, emphasizing less well-recognized clinical findings. RESULTS AND CONCLUSIONS: The phenotype of the prototypic 47,XXY case is well recognized: seminiferous tubule dysgenesis and androgen deficiency. Less well appreciated is the varied expressivity of 47,XXY Klinefelter syndrome, in particular neurological/cognitive perturbations like language and behavioral problems. Effective therapies are available. Reproductive technologies allow 47,XXY men to sire offspring through intracytoplasmic sperm injection (ICSI); however, genetic counseling is complex and success is low. Behavioral and expressive language difficulties are amenable to treatment by androgen therapy and psychological help. Early treatment may be imperative for optimal outcome.

Biomedical Research↗