Chromosome malorientations after meiosis II arrest cause nondisjunction

This study investigated the basis of meiosis II nondisjunction. Cold arrest induced a fraction of meiosis II crane fly spermatocytes to form (n + 1) and (n - 1) daughters during recovery. Live-cell liquid crystal polarized light microscope imaging showed nondisjunction was caused by chromosome malorientation. Whereas amphitely (sister kinetochore fibers to opposite poles) is normal, cold recovery induced anaphase syntely (sister fibers to the same pole) and merotely (fibers to both poles from 1 kinetochore). Maloriented chromosomes had stable metaphase positions near the equator or between the equator and a pole. Syntelics were at the spindle periphery at metaphase; their sisters disconnected at anaphase and moved all the way to a centrosome, as their strongly birefringent kinetochore fibers shortened. The kinetochore fibers of merotelics shortened little if any during anaphase, making anaphase lag common. If one fiber of a merotelic was more birefringent than the other, the less birefringent fiber lengthened with anaphase spindle elongation, often permitting inclusion of merotelics in a daughter nucleus. Meroamphitely (near amphitely but with some merotely) caused sisters to move in opposite directions. In contrast, syntely and merosyntely (near syntely but with some merotely) resulted in nondisjunction. Anaphase malorientations were more frequent after longer arrests, with particularly long arrests required to induce syntely and merosyntely.     

47,XXY karyotype in a patient with Beckwith-Wiedemann syndrome

The present report summarizes the follow-up data from birth up to the age of 14 years in a male patient with Beckwith-Wiedemann syndrome and 47,XXY karyotype.     

Spontaneous testicular neoplasm in mice with testicular feminization

Summary Testicular neoplasms occur spontaneously in androgen insensitive mice with testicular feminization (tfm/y); they are composed of Leydig cells, lipid-laden cells, fibroblastlike cells, and macrophages. The small Leydig cells in the periphery of the tumor are structurally similar to nontumorous tfm/y Leydig cells, whereas centrally located large Leydig cells contain numerous lipid droplets, mitochondria with tubular cristae, and abundant smooth endoplasmic reticulum. The lipid-laden cells exhibit a crescentic nucleus which is displaced toward the periphery of the cytoplasm by a large lipid vacuole. The fibroblastlike cells have a large amount of rough endoplasmic reticulum, lysosomes, free ribosomes, and lipid vacuoles. Macrophages are characterized by numerous layered and dense osmiophilic structures closely associated with crystalshaped bodies. An in vitro study shows that, in comparison with the normal testes, the tfm/y tumors produce significantly less testosterone but a larger quantity of androstenedione. Also, the tumors are capable of converting progesterone to estrone and estradiol-17. The plasma level of testosterone is significantly lower in tumor-bearing animals than in normal littermates, but slightly higher than in the nontumorous tfm/y animals. Since the abnormal steroid enzyme activity is found in both tumor-bearing and nontumorous tfm/y mice, the basic cause of aberrations in sex steroid production appears to be genetic rather than the direct result of alterations in their Leydig cells.     

A 47,XXY female with unusual genitalia

A 47,XXY karyotype was found in a 6-year-old girl. The patient had female external genitalia, clitoromegaly, remnants of the ductus mesonephricus, uterus, and gonads in the labia majora which were determined to be testes by histology. Cytogenetic and DNA analyses suggest that the Y chromosome had a normal structure and that both X chromosomes were of maternal origin. The unusual clinical findings in the patient are discussed.Dedicated to Professor Ulrich Wolf on the occasion of his 60th birthday     

An SRY-negative 47,XXY mother and daughter

Females with XY gonadal dysgenesis are sterile, due to degeneration of the initially present ovaries into nonfunctional streak gonads. Some of these sex-reversal cases can be attributed to mutation or deletion of the SRY gene. We now describe an SRY-deleted 47,XXY female who has one son and two daughters, and one of her daughters has the same 47,XXY karyotype. PCR and FISH analysis revealed that the mother carries a structurally altered Y chromosome that most likely resulted from an aberrant X-Y interchange between the closely related genomic regions surrounding the gene pair PRKX and PRKY on Xp22.3 and Yp11.2, respectively. As a consequence, Yp material, including SRY, has been replaced by terminal Xp sequences up to the PRKX gene. The fertility of the XXY mother can be attributed to the presence of the additional X chromosome that is missing in XY gonadal dysgenesis females. To our knowledge, this is the first human XXY female described who is fertile.     

Synaptonemal complex studies in a mosaic 46,XY/47,XXY male

Summary We describe the results of synaptonemal complex (SCs) studies by light (LM) and electron microscopy (EM) in a sterile 46,XY/47,XXY male mosaic. Meiotic studies showed an arrest at the first spermatocyte level. Pachytene figures showed three types of cells: (1) cells with normal SCs, normal sex vesicle, and a 23,XY constitution; (2) cells with no sex vesicle, normal pairing of SCs, and a 24, (?) constitution; and (3) cells with a normal sex vesicle and fragmented SCs.     

Normal meiosis in two 47,XYY men

Summary Details of testicular histology and meiosis are given for two 47,XYY men, one an oligospermic childless individual, the other a fertile man with near-normal spermatogenic activity in his testes. Examination of the chromosomes at meiosis, with Q and C staining, gave no evidence for the occurrence of the second Y chromosome in the germ line of either individual.     

Prevalence of Klinefelter's syndrome (47,XXY) in a general male population

In a representative sample of 3,840 males examined for military service chromosome examination was made in those with testes equal to or less than 12 ml and those with a stature equal to or greater than 181 cm, as well as in males not recruited because of physical or mental disability. Testes equal to or less than 12 ml were found in 59 patients (1.45%). Three of these males had a 47,XXY karyotype (5.1%), the prevalence among the total sample of 3,840 being 0.78 per 1,000. Hypogonadal signs, except for gynaecomastia, which was only present in one patient, were found in the saem proportion as in 47,XXY males ascertained in institutions and clinics. The results of EEG investigations were alos similar to those found in psychiatric institutions. The intelligence level was comparatively low; none had an IQ above 100. The personality traits corresponded to those found in institutionalized Klinefelter males.     

Psychological characterization of testicular feminization syndrome

Ten cases with testicular feminization syndrome (TFS) diagnosed at the National Institute of Endocrinology and Metabolism, were studied. The patients were interviewed and subjected to the following psychological tests: Raven's Progressive Matrices, the MMPI, the 16PF, and the TAT. Laboratory determinations included: nuclear chromatin, karyotype, FHS, LH, estradiol, testosterone and nitrogen retention test. Intellectual achievement was found normal, and as far as psychological stability is concerned (MMPI) there was no common profile typical of the group. Psychosexual attitudes showed alterations related to acceptance of body image, fears to be unable to maintain the stability of the couple, and lack of a strong maternal drive. Personality profile manifested two outstanding traits in the group: Dominance (E+) and Shrewdness (N+), the former being remarkably high for a female population. A hypothesis is advanced in regard to the psychological alterations of the possible role of partial androgenization of the central nervous system in these patients.     

Occlusion in 47,XXY (Klinefelter syndrome) men.

Occlusal morphology of permanent dentitions in 29 men with a 47,XXY chromosome complement (Klinefelter syndrome) was determined from dental casts. The results showed that a relatively frequent occlusal anomaly was mesial molar occlusion. Incisal open bite was also more common than in controls. Based on the present and previous observations of occlusal anomalies in various sex chromosome anomaly groups and normal controls, it is suggested that the presence of the Y chromosome in the genome is at least as important as the X chromosome for the development of harmonious occlusal morphology. The tendency towards sexual dimorphism in occlusal phenotype might result from a differential effect of the X and Y chromosomes on cellular activity which leads to different growth patterns.     

Cardiac functioning and blood pressure of 47,XYY and 47,XXY men in a double-blind, double-matched population survey.

This paper reports the electrocardiogram measures and blood pressure of 12 men with 47,XYY, 14 men with 47,XXY, and 52 matched controls with 46,XY. The abnormal karyotypes were identified in a systematic population search for XYY and XXY men. The subjects and their matched controls were examined in a double-blind fashion. Electrocardiogram measures of 47,XYY and 47,XXY men were found to differ from those of 46,XY controls. The XYYs had longer P-R intervals, shorter QRS complexes, and nonsignificantly longer R-R intervals than their matched controls. The XXYs showed longer R-R intervals and trends for for prolonged P-R intervals and shorter QRS complexes when compared with their controls. Trends toward increased within-group variability in the XYY and XXY groups were observed in five of six variance tests, suggesting that the sex chromosome aneuploids have a cardiac condition anomaly. Blood pressure measures of 47,XYY and 47,XXY men were found not to differ from those of 46,XY men. None of the measures revealed a significant difference between the XYYs and the XXYs.     

Testicular lipids in mice with testicular feminization

Morphological, histochemical and biochemical studies of the testis of mice with testicular feminization (tfm/y) reveal a large accumulation of lipids in Leydig cells and in Sertoli cells. In Leydig cells of tfm/y mice, lipid droplets do not exhibit the special relationship with smooth endoplasmic reticulum that exists in normal adult Leydig cells. Compared to the surgically-cryptorchid control, the tfm/y testis contains more lipid in Leydig cells but less in Sertoli cells. There are also quantitative differences in testicular lipids in tmf/y and normal testes but no significant differences were noted between tfm/y and surgically-cryptorchid testes. The testes of both the genetically defective and surgically-cryptochid animals contain increased amounts of total lipids and phospholipids, and of free and esterified cholesterols. Exogenous testosterone has no effect on lipids or other characteristics of these cells. The present results suggest that the increased lipids in tfm/y mice result from a genetic disorder that asserts itself (1) in Leydig cells where it is associated with, and is probably a result of, impaired lipid metabolism and steroidogenesis, and (2) in Sertoli cells where it is perhaps attributable to arrested spermatogenesis and impaired steroidogenesis.