Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many studies have shown that congenital absence of the vas deferens (CAVD) is a genital cystic fibrosis transmembrane conductance regulator (CFTR)-mediated phenotype, with a broad spectrum of abnormalities causing male infertility. The genotype of these patients includes mutations in the CFTR gene, e.g. DeltaDeltaF508, R117H and the T5 allele; all of which are commonly found in CAVD. In this study we have screened the entirety of CFTR gene in 47 males with anomalies of the vas deferens: 37 cases of congenital bilateral absence of the vas deferens, three cases of congenital unilateral absence of the vas deferens and seven cases of obstructive azoospermia with hypoplastic vas deferens. Among the 94 chromosomes studied, 65 mutations, of which three are novel (2789+2insA, L1227S, 4428insGA), were identified. The majority of patients (63.8%) had two detectable CFTR gene mutations. Furthermore, high frequencies of the DeltaDeltaF508 mutation (44.7%), the T5 allele (36.2%) and R117H mutation (19.1%) were observed.
Mol Hum Reprod 2000 Dec
PMID:Molecular screening of the CFTR gene in men with anomalies of the vas deferens: identification of three novel mutations. 1110 88

To assess if testicular sperm cryopreservation is a valid alternative to repetition of testicular sperm retrieval techniques, results of a cryopreservation technique in pills have been retrospectively analyzed. Enough motile spermatozoa for ICSI were obtained in 172 from 190 (90.5%) frozen-thawed testicular sperm samples. Overall, 249 couples underwent 390 ICSI cycles, 156 using fresh and 234 using cryopreserved testicular sperm. Mean two-pronuclear fertilization rates per cycle were not significantly different after ICSI with fresh (62.0%) or with cryopreserved (63.2%) spermatozoa. Mean embryo cleavage rate per cycle was higher in the fresh (90.6%) than in the cryopreserved (84.6%) group (P = 0.016). However, clinical pregnancy rates per cycle (28.2% with fresh vs 27.8% with cryopreserved), implantation rates (12.2% vs 13.1%) and ongoing pregnancy rates per cycle (22.4% vs 21.8%) were not significantly different. Cryopreservation of testicular spermatozoa is an effective technique that can be used both in obstructive and in non-obstructive azoospermia.
Mol Cell Endocrinol 2000 Nov 27
PMID:Intracytoplasmic sperm injection with cryopreserved testicular spermatozoa. 1115 47

Men with azoospermia can now be treated using testicular sperm aspiration (TESA). New aspirations, in subsequent cycles, may be avoided using cryopreservation. Conventional sperm freezing techniques are not suitable for TESA samples with a small number of spermatozoa. Testicular spermatozoa were obtained from 10 azoospermic men undergoing TESA for a diagnostic objective. Two different freezing protocols were performed according to the number of spermatozoa found in the final suspension: between 100-2000, we used TEST yolk buffer with glycerol, adding it to testicular sperm (Method I); for less than 100, we injected them into cell-free human zona pellucida before adding a freezing medium (Method II). Sperm and motility recovery rates were 1% and 32.3%, and 88.2% and 26.6% for methods I and II respectively. The fertilisation rate was 13.3% and 23% for methods I and II respectively. This study represents our preliminary experience in freezing testicular spermatozoa collected by TESA. Preliminary observations show that it is possible to freeze a few testicular spermatozoa inside evacuated zona pellucida.
Mol Cell Endocrinol 2000 Nov 27
PMID:Freezing a few testicular spermatozoa retrieved by TESA. 1115 49

The objective of this study was to elucidate the cause of the spermatogenic defect in idiopathic azoospermia and non-mosaic type of Klinefelter syndrome. Genomic DNAs from 9 cases of Korean idiopathic azoospermia and 6 of Korean non-mosaic type of Klinefelter syndrome were used for the detection of Y chromosome microdeletions by polymerase chain reaction using 60 primers. Microdeletions of the Y chromosome were found in 1 of 9 (11.1%) patients with idiopathic azoospermia, whereas none was deleted in non-mosaic type of Klinefelter syndrome. This result suggests that Y chromosome microdeletions could be one of the etiologic factors in idiopathic azoospermia.
Exp Mol Med 2000 Dec 31
PMID:Y chromosome microdeletions in idiopathic azoospermia and non-mosaic type of Klinefelter syndrome. 1119 Feb 76

Because a microdeletion containing the DAZ gene is the most frequently observed deletion in infertile men, the DAZ gene was considered a strong candidate for the azoospermia factor. A recent evolutionary analysis, however, suggested that DAZ was free from functional constraints and consequently played little or no role in human spermatogenesis. The major evidence for this surprising conclusion is that the nonsynonymous substitution rate is similar to the synonymous rate and to the rate in introns. In this study, we reexamined the evolution of the DAZ gene family by using maximum-likelihood methods, which accommodate variable selective pressures among sites or among branches. The results suggest that DAZ is not free from functional constraints. Most amino acids in DAZ are under strong selective constraint, while a few sites are under diversifying selection with nonsynonymous/ synonymous rate ratios (d(N)/d(S)) well above 1. As a result, the average d(N)/d(S) ratio over sites is not a sensible measure of selective pressure on the protein. Lineage-specific analysis indicated that human members of this gene family were evolving by positive Darwinian selection, although the evidence was not strong.
Mol Biol Evol 2001 Apr
PMID:Positive and negative selection in the DAZ gene family. 1126 3

Cellular localization of oestrogen receptor alpha (ERalpha) and beta (ERbeta) proteins were studied in human testis samples using immunohistochemistry, and the expression of the corresponding mRNA was examined with reverse transcription-polymerase chain reaction (RT-PCR). Seven men, aged 28-48 years, who underwent diagnostic testicular biopsy because of azoospermia or to give spermatozoa for intracytoplasmic injection for infertility treatment, donated tissue for the study. One of them had anejaculation but normally functioning testes, and one was diagnosed as having Sertoli cell-only syndrome (SCOS). In addition, expression of ERbeta protein was examined in one testis sample obtained from a man undergoing a sex change operation. Strong ERbeta immunoreactivity was detected in the nuclei of spermatogonia, spermatocytes and early developing spermatids. Elongating spermatids, mature spermatozoa, Sertoli and Leydig cells were all negative for ERbeta. The presence of ERbeta protein was confirmed in Western analysis. With RT-PCR, both wild-type ERbeta and ERbetacx, the isoform which represses wild-type ER function, were easily detected. In most cases, ERbetacx mRNA was more abundantly expressed than wild-type ERbeta. The patient with SCOS expressed neither ERbeta isoform. Neither ERalpha protein nor ERalpha mRNA was detected in any of the samples. We conclude that in the human testis, ERbeta is likely to be the ER that mediates the effects of oestrogen.
Mol Hum Reprod 2001 Jun
PMID:Localization of oestrogen receptors alpha and beta in human testis. 1138 5

PRY (PTP-BL related on the Y chromosome) has been proposed as a candidate spermatogenesis gene. We report the characterization of the genomic structure, the number of copies on the Y chromosome and the expression of the gene. By comparison of the cDNA sequence with the genomic sequence, five exons were identified. Analysis of GenBank-derived clones on the Y chromosome revealed the presence of two full-length copies in azoospermia factor region b (AZFb) (PRY1 and PRY2) and two shorter versions of the PRY gene containing exons 3, 4 and 5 in AZFc (PRY3 and PRY4). A clone containing sequences homologous to exons 3, 4 and 5 is located in area 5L (between AZFa and AZFb), a clone containing a sequence homologous to exon 5 is located in area 5M (in AZFb) and a clone containing a fragment homologous to exon 3 is located in 6F. A repeat structure of exons 1 and 2 is present on the short arm of the Y chromosome as well as on the long arm. PRY1 and PRY2, two gene copies that are located in AZFb, a region often deleted in patients with severe male infertility, were shown to be expressed in the testis. PRY may therefore play an important role in spermatogenesis.
Mol Hum Reprod 2001 Jul
PMID:Characterization of the genomic organization, localization and expression of four PRY genes (PRY1, PRY2, PRY3 and PRY4). 1142 Mar 82

Inhibin B is a testicular peptide hormone that regulates FSH secretion in a negative feedback loop. In males serum levels of inhibin B are detectable throughout life with prominent changes in the first year of life and during puberty. Serum inhibin B is normally detectable throughout childhood where it is a direct marker of the presence and function of Sertoli cells. The inhibin B analysis has proven useful in the diagnosis of patients with non-palpable testes. Undetectable or low inhibin B levels are observed in boys with either congenital or acquired absence of testicular tissue whereas normal or near-normal levels are seen in cryptorchidism and disorders with preserved Sertoli cell function in spite of absence of germ cells or impaired androgen biosynthesis or action. During puberty a developmental change in the regulation of serum inhibin B occurs. In contrast to childhood inhibin B levels, inhibin B production in adult men is dependent on the presence of certain germ cells in the seminiferous tubules, most likely involving the pachytene spermatocytes and early spermatids. Thus, in adult men serum inhibin B levels are closely related to spermatogenesis with undetectable or low levels observed in SCO syndrome and early stage spermatogenic arrest whereas normal or near normal levels are observed in men with late stage spermatogenic arrest or obstructive forms of azoospermia. These clinical findings are in accordance with immuno-histological studies of the expression of inhibin B subunits in human testis.
Mol Cell Endocrinol 2001 Jun 30
PMID:Serum inhibin B levels during male childhood and puberty. 1145 78

The current generation of inhibin assays have allowed the demonstration that inhibin B is the long-postulated testicular factor comprising the feedback inhibitory pathway between the testis and FSH secretion. The inverse relationship between inhibin B and FSH secretion is seen in both normal men and in testicular pathologies. Although inhibin B concentrations are increased by gonadotrophin administration, adult secretion is only partly gonadotrophin dependent and appears more closely related to the presence of germ cells. Thus, inhibin B concentrations are maintained at least at 30% of normal following gonadotrophin suppression, but fall to undetectable levels following loss of all germ cells, e.g. by testicular irradiation. The direct positive correlation between inhibin B and sperm concentration in normal men indicates that inhibin B quantitatively reflects the number of spermatozoa being released. Data from studies of infertile men undergoing testicular biopsy is providing information as to the particular stages of spermatogenesis involved. These intercellular relationships may underlie the relative resistance of inhibin B to suppression by some hormonal contraceptive regimens, despite azoospermia being induced. Inhibin B is also present in seminal plasma. There is a far wider range of concentration in seminal plasma than in blood and the significant relationship with sperm concentration indicates that inhibin secretion into the ejaculate is a marker of the functional activity of the seminiferous tubule. This relationship with sperm production may be a useful marker in some contexts, as changes are more dynamic than in the circulating hormone.
Mol Cell Endocrinol 2001 Jun 30
PMID:Clinical studies: inhibin in the adult male. 1145 79

In man, infertility is associated with microdeletions of specific regions of the long arm of the Y chromosome. This indicates that factors encoded by the Y chromosome are necessary for spermatogenesis. However, the majority of men with either idiopathic azoospermia or oligozoospermia have grossly intact Y chromosomes and the underlying causes of their infertility are unknown. We hypothesized that some of these individuals may carry other rearrangements or sequence variants on the non-recombining region of the Y chromosome that may be associated with reduced spermatogenesis. To test this hypothesis, we typed the Y chromosome in a group of Danish men with known sperm counts and compared the haplotype distribution with that of a group of unselected Danish males. We found that one class of Y chromosome, referred to as haplogroup 26+, was significantly overrepresented (27.9%; P < 0.001) in the group of men with either idiopathic oligozoospermia (defined as <20 x 10(6 )sperm/ml) or azoospermia compared to the control Danish male population (4.6%). This study defines, for the first time, a class of Y chromosome that is at risk for infertility in a European population. This observation suggests that selection may be indeed active on the Y chromosome, at least in the Danish population, raising the possibility that it could alter the pattern of Y chromosome haplotype distribution in the general population.
Hum Mol Genet 2001 Sep 01
PMID:Identification of a Y chromosome haplogroup associated with reduced sperm counts. 1155 23


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