Klinefelter Syndrome: A form of male HYPOGONADISM, characterized by the presence of an extra X CHROMOSOME, small TESTES, seminiferous tubule dysgenesis, elevated levels of GONADOTROPINS, low serum TESTOSTERONE, underdeveloped secondary sex characteristics, and male infertility (INFERTILITY, MALE). Patients tend to have long legs and a slim, tall stature. GYNECOMASTIA is present in many of the patients. The classic form has the karyotype 47,XXY. Several karyotype variants include 48,XXYY; 48,XXXY; 49,XXXXY, and mosaic patterns ( 46,XY/47,XXY; 47,XXY/48,XXXY, etc.).Sperm Retrieval: Procedures to obtain viable sperm from the male reproductive tract, including the TESTES, the EPIDIDYMIS, or the VAS DEFERENS.Azoospermia: A condition of having no sperm present in the ejaculate (SEMEN).Sex Chromosome Disorders: Clinical conditions caused by an abnormal sex chromosome constitution (SEX CHROMOSOME ABERRATIONS), in which there is extra or missing sex chromosome material (either a whole chromosome or a chromosome segment).Gynecomastia: Enlargement of the BREAST in the males, caused by an excess of ESTROGENS. Physiological gynecomastia is normally observed in NEWBORNS; ADOLESCENT; and AGING males.Chromosomes, Human, X: The human female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in humans.Sex Chromosome Aberrations: Abnormal number or structure of the SEX CHROMOSOMES. Some sex chromosome aberrations are associated with SEX CHROMOSOME DISORDERS and SEX CHROMOSOME DISORDERS OF SEX DEVELOPMENT.Chromosomes, Human, Y: The human male sex chromosome, being the differential sex chromosome carried by half the male gametes and none of the female gametes in humans.Gonadal Dysgenesis, 46,XX: The 46,XX gonadal dysgenesis may be sporadic or familial. Familial XX gonadal dysgenesis is transmitted as an autosomal recessive trait and its locus was mapped to chromosome 2. Mutation in the gene for the FSH receptor (RECEPTORS, FSH) was detected. Sporadic XX gonadal dysgenesis is heterogeneous and has been associated with trisomy-13 and trisomy-18. These phenotypic females are characterized by a normal stature, sexual infantilism, bilateral streak gonads, amenorrhea, elevated plasma LUTEINIZING HORMONE and FSH concentration.Karyotyping: Mapping of the KARYOTYPE of a cell.Primed In Situ Labeling: A technique that labels specific sequences in whole chromosomes by in situ DNA chain elongation or PCR (polymerase chain reaction).Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. In a normally diploid cell (DIPLOIDY) the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is MONOSOMY (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is TRISOMY (symbol: 2N+1).XYY Karyotype: Abnormal genetic constitution in males characterized by an extra Y chromosome.Syndrome: A characteristic symptom complex.Infertility, Male: The inability of the male to effect FERTILIZATION of an OVUM after a specified period of unprotected intercourse. Male sterility is permanent infertility.Mosaicism: The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single ZYGOTE, as opposed to CHIMERISM in which the different cell populations are derived from more than one zygote.Oligospermia: A condition of suboptimal concentration of SPERMATOZOA in the ejaculated SEMEN to ensure successful FERTILIZATION of an OVUM. In humans, oligospermia is defined as a sperm count below 20 million per milliliter semen.Breast Neoplasms, Male: Any neoplasms of the male breast. These occur infrequently in males in developed countries, the incidence being about 1% of that in females.Fathers: Male parents, human or animal.Testis: The male gonad containing two functional parts: the SEMINIFEROUS TUBULES for the production and transport of male germ cells (SPERMATOGENESIS) and the interstitial compartment containing LEYDIG CELLS that produce ANDROGENS.Testosterone: A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.In Situ Hybridization, Fluorescence: A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.
Polysomy: Polysomy is a condition found in many species, including fungi, plants, insects, and mammals, in which an organism has at least one more chromosome than normal, i.e.AzoospermiaGynecomastiaPRINS (gene): PRINS (psoriasis associated RNA induced by stress) is a long non-coding RNA. Its expression is induced by stress, and it may have a protective role in cells exposed to stress.Malformative syndrome: A malformative syndrome (or malformation syndrome) is a recognizable pattern of congenital anomalies that are known or thought to be causally related (VIIth International Congress on Human Genetics).Male infertilityConfined placental mosaicism: Confined placental mosaicism (CPM) represents a discrepancy between the chromosomal makeup of the cells in the placenta and the cells in the baby. CPM was first described by Kalousek and Dill in 1983.FNA Mapping: Fine needle aspiration (FNA) cytology has been used to examine pathological human tissue from various organs for over 100 years.,Posner C.Blood–testis barrier: The blood–testis barrier is a physical barrier between the blood vessels and the seminiferous tubules of the animal testes. The name "blood-testis barrier" is misleading in that it is not a blood-organ barrier in a strict sense, but is formed between Sertoli cells of the seminiferous tubule and as such isolates the further developed stages of germ cells from the blood.Prenatal testosterone transfer: Prenatal Testosterone Transfer (also known as prenatal androgen transfer or prenatal hormone transfer) refers to the phenomenon in which testosterone synthesized by a developing male fetus transfers to one or more developing fetuses within the womb and influences development. This typically results in the partial masculinization of specific aspects of female behavior, cognition, and morphology, though some studies have found that testosterone transfer can cause an exaggerated masculinization in males.
(1/226) Germ cell development in the XXY mouse: evidence that X chromosome reactivation is independent of sexual differentiation.
Prior to entry into meiosis, XX germ cells in the fetal ovary undergo X chromosome reactivation. The signal for reactivation is thought to emanate from the genital ridge, but it is unclear whether it is specific to the developing ovary. To determine whether the signals are present in the developing testis as well as the ovary, we examined the expression of X-linked genes in germ cells from XXY male mice. To facilitate this analysis, we generated XXY and XX fetuses carrying X chromosomes that were differentially marked and subject to nonrandom inactivation. This pattern of nonrandom inactivation was maintained in somatic cells but, in XX as well as XXY fetuses, both parental alleles were expressed in germ cell-enriched cell populations. Because testis differentiation is temporally and morphologically normal in the XXY testis and because all germ cells embark upon a male pathway of development, these results provide compelling evidence that X chromosome reactivation in fetal germ cells is independent of the somatic events of sexual differentiation. Proper X chromosome dosage is essential for the normal fertility of male mammals, and abnormalities in germ cell development are apparent in the XXY testis within several days of X reactivation. Studies of exceptional germ cells that survive in the postnatal XXY testis demonstrated that surviving germ cells are exclusively XY and result from rare nondisjunctional events that give rise to clones of XY cells. (+info)
(2/226) Birth of a healthy neonate following the intracytoplasmic injection of testicular spermatozoa from a patient with Klinefelter's syndrome.
Klinefelter's syndrome is one of the known causes of azoospermia or cryptoazoospermia, and it may present in non-mosaic (47,XXY) or mosaic (47,XXY/46,XY) form. The likelihood of finding spermatozoa in the ejaculate or testicular tissue of patients with mosaic Klinefelter's syndrome is low, and with the non-mosaic form, even lower. We describe a patient with non-mosaic Klinefelter in whom initially non-motile spermatozoa were derived from searching the ejaculate. Ten mature oocytes were injected, but none was fertilized. Subsequently, testicular biopsy was undertaken in order to collect spermatozoa for oocyte injection. Fifteen motile sperm cells were found and injected. Nine oocytes were fertilized and cleaved; three embryos were transferred into the uterine cavity. The woman conceived and following a normal pregnancy delivered a healthy child. Genetic analysis of the neonate disclosed a normal 46,XY karyotype. Non-motile spermatozoa in the ejaculate did not prove their fertilization potential, but their presence did not exclude finding motile, fertile spermatozoa in the testicular tissue in a non-mosaic Klinefelter patient. This report is further evidence that normal spermatozoa with fertilization potential are produced in the testes of patients with Klinefelter's syndrome. (+info)
(3/226) Klinefelter's syndrome in the male infertility clinic.
The clinical features of patients with Klinefelter's syndrome attending a male infertility clinic have been investigated in order to consider their assisted reproduction treatment options. Over 12 years, a total of 148 patients with sterility due to azoospermia had Klinefelter's syndrome. Eight patients were shown by fluorescence in-situ hybridization (FISH) on metaphase spreads to be mosaic (46,XY/47,XXY), and 140 patients showed only 47,XXY. Small testes were observed in 95% of patients and gynaecomastia was seen in 12.4%. Half of the patients showed hypergonadotrophic hypogonadism, while others showed normogonadism (usually hypergonadotrophic). Spermatozoa were observed in semen from one patient with mosaicism and one without. Three-colour FISH revealed hyperploidy in 2.7% and 2.3% of these spermatozoa respectively. Multiple-site testicular biopsies in five recent patients were performed and yielded a specimen with round and elongated spermatids in one patient with 47,XXY karyotype. This sample was cryopreserved for future intracytoplasmic sperm injection. At follow-up, 46% of couples had chosen artificial insemination with donor sperm, and none had chosen adoption. Two patients developed testicular tumours, one a mature teratoma and the other a Leydig cell tumour. Two patients required androgen replacement therapy. (+info)
(4/226) Fertilization and pregnancy outcome with intracytoplasmic sperm injection for azoospermic men.
The evident ability of the intracytoplasmic sperm injection (ICSI) procedure to achieve high fertilization and pregnancy rates regardless of semen characteristics has induced its application with spermatozoa surgically retrieved from azoospermic men. Here, ICSI outcome was analysed in 308 cases according to the cause of azoospermia; four additional cycles were with cases of necrozoospermia. All couples were genetically counselled and appropriately screened. Spermatozoa were retrieved by microsurgical epididymal aspiration or from testicular biopsies. Epididymal obstructions were considered congenital (n = 138) or acquired (n = 103), based on the aetiology. Testicular sperm cases were assessed according to the presence (n = 14) or absence (n = 53) of reproductive tract obstruction. The fertilization rate using fresh or cryopreserved epididymal spermatozoa was 72.4% of 911 eggs for acquired obstructions, and 73.1% of 1524 eggs for congenital cases; with clinical pregnancy rates of 48.5% (50/103) and 61.6% (85/138) respectively. Spermatozoa from testicular biopsies fertilized 57.0% of 533 eggs in non-obstructive cases compared to 80.5% of 118 eggs (P = 0.0001) in obstructive azoospermia. The clinical pregnancy rate was 49.1% (26/53) for non-obstructive cases and 57.1% (8/14) for testicular spermatozoa obtained in obstructive azoospermia, including three established with frozen-thawed testicular spermatozoa. In cases of obstructive azoospermia, fertilization and pregnancy rates with epididymal spermatozoa were higher than those achieved using spermatozoa obtained from the testes of men with non-obstructive azoospermia. (+info)
(5/226) Meiotic aneuploidy in the XXY mouse: evidence that a compromised testicular environment increases the incidence of meiotic errors.
Male mammals with two X chromosomes are sterile due to the loss of virtually all germ cells in the differentiating testis. The survival of rare germ cells, however, can give rise to patches of normal-appearing spermatogenesis in the adult testis. Intracytoplasmic sperm injection (ICSI) makes possible the establishment of a pregnancy using spermatozoa from severely oligozoospermic men and, indeed, has been successful using spermatozoa from human 47,XXY (Klinefelter syndrome) males. The risk of an abnormal pregnancy, however, may be significantly increased since several studies have demonstrated elevated levels of aneuploidy in spermatozoa from Klinefelter syndrome men. This has been suggested to reflect the consequences of meiotic segregation in XXY germ cells; however, it is also possible that it is a consequence of abnormalities in meiotic regulation in the XXY testis. We have addressed this question experimentally in the XXY male mouse. Analysis of testicular spermatozoa from XXY and control males demonstrates a significant increase in meiotic aneuploidy in the XXY mouse. Since previous studies have demonstrated that germ cells in the adult XXY testis are exclusively XY, the meiotic abnormalities observed must be attributable to segregation errors in XY germ cells. These findings have potential significance for ICSI pregnancies using spermatozoa from other types of male factor infertility patients, since they raise the possibility that increased meiotic errors are a generalized feature of the severely oligozoospermic testis. (+info)
(6/226) Developmental and genetic disorders in spermatogenesis.
The most common cause of male infertility is idiopathic. Fresh insights based on genetic and molecular analysis of the human genome permit classification of formerly unexplained disorders in spermatogenesis. In this article, we review new procedures that expand diagnostic and therapeutic approaches to male infertility. Recombinant DNA technology makes it possible to detect specific chromosomal and/or genetic defects among infertile patients. The identification of genes linked to disorders in spermatogenesis and male sexual differentiation has increased exponentially in the past decade. Genetic defects leading to male factor infertility can now be explained at the molecular level, even though the germ cell profile of infertile patients is too variable to permit classification of the clinical phenotype. Increasing knowledge of genes that direct spermatogenesis provides important new information about the molecular and cellular events involved in human spermatogenesis. Molecular analysis of chromosomes and/or genes of infertile patients offers unique opportunities to uncover the aetiology of genetic disorders in spermatogenesis. Increasing numbers of cases, previously classified as idiopathic, can now be diagnosed to facilitate the treatment of infertile men. Advanced knowledge also poses ethical dilemmas, since children conceived with assisted reproductive technologies such as intracytoplasmic sperm injection (ICSI) are at risk for congenital abnormalities, unbalanced complements of chromosomes and male infertility. (+info)
(7/226) Chromosome abnormalities in a referred population for suspected chromosomal aberrations: a report of 4117 cases.
A cytogenetic study was performed on 4,117 Korean patients referred for suspected chromosomal abnormalities. Chromosome aberrations were identified in 17.5% of the referred cases. The most common autosomal abnormality was Down syndrome and Turner syndrome in abnormalities of sex chromosome. The proportions of different karyotypes in Down syndrome (trisomy 21 92.5%, translocation 5.1%, mosaic 2.4%) were similar to those reported in other countries. However, it was different in Turner syndrome (45, X 28.1%, mosaic 50.8%, 46, X, del (Xq) 4.4%, 46, X, i (Xq) 16.7%), in which proportions of mosaics and isochromosome, 46, X, i(Xq), were higher than those reported in other countries. In structural chromosome aberrations of autosome, translocation was the most common (43.6%), and duplication (21.3%), deletion (14.4%), marker chromosome (7.9%) and ring chromosome (4.0%) followed in order of frequency. Rates of several normal variant karyotypes were also described. Inversion of chromosome 9 was observed in 1.7% of total referred cases. (+info)
(8/226) Klinefelter's syndrome accompanied by mixed connective tissue disease and diabetes mellitus.
We report a rare case of Klinefelter's syndrome (KS) with mixed connective tissue disease (MCTD), diabetes mellitus (DM) and several endocrine disorders. A 57-year-old man presented with polyarthritis and tapering fingers with Raynaud's phenomenon on admission. In addition to a karyotype of 47, XXY, a marked restrictive change in respiratory functional test, a myogenic pattern in electromyogram, the positive tests for anti-RNP antibody indicated that this was a case of KS complicated with MCTD. The patients also presented DM with insulin resistance, hyperprolactinemia, slight primary hypothyroidism and hypoadrenocorticism. The mechanism for these coincidences remains to be elucidated. (+info)