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

The Thr54Ala polymorphism of the deleted-in-azoospermia-like (DAZL) protein has been associated with susceptibility to spermatogenic failure in the Taiwanese population. We used single-strand conformation polymorphism and restriction fragment analyses to investigate the presence of the A-->G transition in exon 3 of the DAZL gene in 95 infertile Italian patients. The patients had oligozoospermia or non-obstructive azoospermia with different degrees of testicular cytological picture. The allele carrying T54A polymorphism was not present in this group of patients nor in 63 controls, indicating that the frequency of this putative mutation is <1% in Italy. Since the Italian population usually shows allelic frequencies similar to the other Caucasian populations, we suggest that the T54A allele might play a role in infertility only in Taiwanese or Asiatic individuals.
Mol Hum Reprod 2004 Aug
PMID:Lack of the T54A polymorphism of the DAZL gene in infertile Italian patients. 1522 Apr 64

The spermatogenesis locus azoospermia factor (AZF) in Yq11 has been mapped to three microdeletion intervals designated as AZFa, AZFb, and AZFc. They are caused by intrachromosomal recombination events between large homologous repetitive sequence blocks, and AZFc microdeletions are now recognised as the most frequent known genetic lesion causing male infertility. However, in the same Y-region, large genomic heterogeneities are also observed in fertile men, and only complete AZFa and AZFb deletions are associated with a specific testicular pathology. Partial AZF deletions are associated with variable pathologies and partial AZFc deletions may even have no impact on male fertility. This suggests a genetic redundancy of the multi-copy genes in AZFb and AZFc and a causative relationship between the occurrence of first microdeletions then macrodeletions in the repetitive structure of Yq11 where large palindromes are probably promoting multiple gene conversions and AZF rearrangements.
Mol Cell Endocrinol 2004 Sep 30
PMID:Genomic heterogeneity and instability of the AZF locus on the human Y chromosome. 1535 75

The molecular aetiology of male subfertility is still unknown in the majority of cases and it is thought that multiple genes are involved. One of the genes that might play a role in male reproductive function is the protein C inhibitor (PCI) gene. In mice the presence of PCI is an absolute requirement for reproduction. In this study we performed a mutation screen of the PCI gene in subfertile men with severe teratozoospermia or idiopathic azoospermia. Male partners of subfertile couples with idiopathic azoospermia (n = 27) or teratozoospermia (n = 34) and men with normozoospermia (n = 34) were screened for mutations in the PCI gene by direct sequencing. Nine nucleotide variants found in the patients were not present in the initial control group and were therefore screened in an additional control group of 80 men with normozoospermia by restriction fragment length polymorphism analysis. In addition, PCI antigen levels were measured in the seminal plasma of the patients in which a potential mutation was found. In total, three new variants were exclusively present in men with idiopathic azoospermia, but are not likely to have caused the patients' phenotypes. In addition, the PCI antigen levels in seminal plasma of these three patients were not decreased. The fact that we were not able to detect causal mutations in the PCI gene does not necessarily lead to the conclusion that the PCI protein is not involved in human male fertility, but the results of our study indicate that mutations in the human PCI gene are not a common cause of reduced semen parameters in men.
Mol Hum Reprod 2004 Nov
PMID:Absence of mutations in the PCI gene in subfertile men. 1537 16

Pantothenate kinase-associated neurodegeneration (PKAN, formerly known as Hallervorden-Spatz syndrome) is a rare but devastating neurodegenerative disorder, resulting from an inherited defect in coenzyme A biosynthesis. As pathology in the human condition is limited to the central nervous system, specifically the retina and globus pallidus, we have generated a mouse knock-out of the orthologous murine gene (Pank2) to enhance our understanding of the mechanisms of disease and to serve as a testing ground for therapies. Over time, the homozygous null mice manifest retinal degeneration, as evidenced by electroretinography, light microscopy and pupillometry response. Specifically, Pank2 mice show progressive photoreceptor decline, with significantly lower scotopic a- and b-wave amplitudes, decreased cell number and disruption of the outer segment and reduced pupillary constriction response when compared with those of wild-type littermates. Additionally, the homozygous male mutants are infertile due to azoospermia, a condition that was not appreciated in the human. Arrest occurs in spermiogenesis, with complete absence of elongated and mature spermatids. In contrast to the human, however, no changes were observed in the basal ganglia by MRI or by histological exam, nor were there signs of dystonia, even after following the mice for one year. Pank2 mice are 20% decreased in weight when compared with their wild-type littermates; however, dysphagia was not apparent. Immunohistochemistry shows staining consistent with localization of Pank2 to the mitochondria in both the retina and the spermatozoa.
Hum Mol Genet 2005 Jan 01
PMID:Deficiency of pantothenate kinase 2 (Pank2) in mice leads to retinal degeneration and azoospermia. 1552 57

Deletions of the Y chromosome are a significant cause of spermatogenic failure. Three major deletion intervals have been defined and termed AZFa, AZFb and AZFc. Here, we report an unusual case of a proximal AZFb deletion that includes the Y chromosome palindromic sequence P4 and a novel heat shock factor (HSFY). This deletion neither include the genes EIF1AY, RPS4Y2 nor copies of the RBMY1 genes. The individual presented with idiopathic azoospermia. We propose that deletions of the testis-specific HSFY gene family may be a cause of unexplained cases of idiopathic male infertility. This deletion would not have been detected using current protocols for Y chromosome microdeletion screens, therefore we recommend that current screening protocols be extended to include this region and other palindrome sequences that contain genes expressed specifically in the testis.
Mol Hum Reprod 2005 Apr
PMID:A deletion of a novel heat shock gene on the Y chromosome associated with azoospermia. 1573 97

A reciprocal translocation between the long arm of the Y chromosome and the long arm of chromosome 1 was observed in an infertile man with non-obstructive azoospermia. The study was performed using a combination of techniques: immunocytogenetic analysis, which allows the detection of synaptonemal complexes (SCs) and recombination sites (MLH1) simultaneously, and fluorescence in-situ hybridization analysis. Meiotic pairing analysis on 100 pachytene spreads showed the presence of a quadrivalent containing chromosomes 1 and Y. There were many abnormalities in chromosome pairing and recombination. These abnormalities included a great reduction of recombination events (as many as one fifth of the SCs had no MLH1 foci), and high proportions of unpaired regions and discontinuities in the SCs. We discuss the possibility that infertility in this patient may be due to transcriptional repression of part of chromosome 1 involved in the translocation, silencing some genes necessary for the progression of meiosis and causing defective meiotic pairing and recombination.
Mol Hum Reprod 2005 May
PMID:Meiotic studies in an azoospermic human translocation (Y;1) carrier. 1584 26

Testicular sperm extraction (TESE) combined with ICSI is used to treat azoospermia. However, the factors that influence the outcome of ICSI in this situation are ill-defined. We sought to investigate the expression of protamine 1 (PRM1) and protamine 2 (PRM2) transcripts in testicular spermatids from obstructive and non-obstructive azoospermic men with impaired spermatogenesis. The relationship between PRM1 and PRM2 transcript levels and the TESE-ICSI outcome was evaluated. The cellular expression of PRM1 and PRM2 mRNAs in single testicular spermatids from 41 azoospermic patients (in whom testicular spermatozoa were subsequently recovered and submitted for TESE-ICSI) was determined by radioactive in situ hybridization. Group I contained seven men with congenital, obstructive azoospermia and whose testicular biopsies indicated quantitatively normal spermatogenesis. Group II consisted of 18 azoospermic men with moderately impaired spermatogenesis. Sixteen men with non-obstructive azoospermia and severely deranged spermatogenesis (i.e. mixed atrophy with small foci of spermatids and spermatozoa) constituted group III. The spermatids of men with severely deranged spermatogenesis exhibited significant lower PRM1 mRNA expression than in the other patient groups. There were no significant inter-group differences in PRM2 mRNA expression. Spermatid PRM1 expression was lower in non-pregnant couples than in pregnant couples. The low number of spermatids in cases of mixed atrophy with small spermatogenic foci is associated with significantly lower PRM1 expression and a lower pregnancy rate. These results emphasize the role of PRM1 as a potentially critical factor in post-ICSI embryonic development.
Mol Hum Reprod 2005 May
PMID:Cellular expression of protamine 1 and 2 transcripts in testicular spermatids from azoospermic men submitted to TESE-ICSI. 1584 27

In humans, the Deleted in Azoospermia Like (DAZL) gene is believed to function in the development of primordial germ cells and in germ cell differentiation and maturation because the expression of DAZL is only found in the germ and non-germ lineage of the reproductive system and in embryonic stem (ES) cells. The present study examined the presence of DAZL transcripts in the last stages of oocyte maturation, in ES cells, and throughout the preimplantation development; the link between gametes and ES cells. The finding of DAZL transcripts in the last stages of oogenesis and during the first two cell cycles of the preimplantation development was expected, because DAZL is a germ cell marker and the transcripts present at that time are generally encoded by the maternal genome. During the third cell cycle, DAZL showed a variable expression pattern, which may point to the maternal to embryonic transition. After the third cell cycle, transcripts were again consistently detected, suggesting embryonic DAZL transcription. In blastocysts, DAZL transcripts were only detected in those of good quality and this as well in the inner cell mass (ICM) as in the trophectoderm (TE). The presence of DAZL transcripts in the ICM and in ES cells was not surprising since both can lead to the formation of germ cells, but TE cells cannot. The quality-related expression of DAZL in blastocysts, and especially its trophectodermal expression, might imply other functions for DAZL beyond germ cell development.
Mol Hum Reprod 2005 Jun
PMID:DAZL expression in human oocytes, preimplantation embryos and embryonic stem cells. 1587 66

AF5q31 (also called MCEF) was identified by its involvement in chromosomal translocation with the gene MLL (mixed lineage leukemia), which is associated with infant acute lymphoblastic leukemia. Several potential roles have been proposed for AF5q31 and other family genes, but the specific requirements of AF5q31 during development remain unclear. Here, we show that AF5q31 is essential for spermatogenesis. Although most AF5q31-deficient mice died in utero and neonatally with impaired embryonic development and shrunken alveoli, respectively, 13% of AF5q31-deficient mice thrived as wild-type mice did. However, the male mice were sterile with azoospermia. Histological examinations revealed the arrest of germ cell development at the stage of spermiogenesis, and virtually no spermatozoa were seen in the epididymis. AF5q31 was found to be preferentially expressed in Sertoli cells. Furthermore, mutant mice displayed severely impaired expression of protamine 1, protamine 2, and transition protein 2, which are indispensable to compact the haploid genome within the sperm head, and an increase of apoptotic cells in seminiferous tubules. Thus, AF5q31 seems to function as a transcriptional regulator in testicular somatic cells and is essential for male germ cell differentiation and survival. These results may have clinical implications in the understanding of human male infertility.
Mol Cell Biol 2005 Aug
PMID:Infertility with defective spermiogenesis in mice lacking AF5q31, the target of chromosomal translocation in human infant leukemia. 1602 15

The DAZL (DAZ-like) gene is suggested to be an ancestral gene of the DAZ (deleted in azoospermia) gene on the Y chromosome, which is a strong candidate for the azoospermic factor. Recently, it has been reported that the T54A (Thr54-->Ala) polymorphism in exon 3 of the DAZL gene is associated with spermatogenic failure in the Taiwanese population. In this study, to investigate whether this polymorphism is associated with spermatogenic failure in Japanese males, we analysed genomic DNA derived from 234 patients with azoospermia or oligozoospermia and 131 fertile controls. The T54A polymorphism was completely absent in both the patients and the controls. The T12A (Thr12-->Ala) polymorphism in exon 2 of the DAZL gene was found at a similar frequency in the patients and controls, 15.4% and 13.7%, respectively (P = 0.67). However, the frequency of T12A was higher for the azoospermic (20.5%) than oligozoospermic (9.6%) individuals in infertile men without DAZ deletions, although statistical difference was not so apparent (chi2 test: P = 0.037, OR = 2.413, 95% CI = 1.035-5.629; Yate's chi2 test: P = 0.058, OR = 2.319, 95% CI = 0.973-6.166). Our results show that the T54A polymorphism in DAZL has no major role in Japanese males with azoospermia or oligozoospermia. The distribution of the T54A polymorphism may be restricted to the narrow area including Taiwan.
Mol Hum Reprod 2005 Jul
PMID:Survey of the two polymorphisms in DAZL, an autosomal candidate for the azoospermic factor, in Japanese infertile men and implications for male infertility. 1612 80


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>