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)

Modifier of rudimentaryp1 (mod(r)p1) is a hybrid dysgenesis-induced mutation isolated as a suppressor of rhd1, a hypomorphic rudimentary(r) allele in Drosophila melanogaster.mod(r)p1 has opposite effects on two of the rudimentary mutant phenotypes. It suppresses the wing truncation associated with hypomorphic r alleles, which was the phenotype used to isolate it. On the other hand, it does not suppress the sterility of r females and in fact decreases the fertility of wild-type females. This infertility is associated with a drastic decrease in r expression in mod(r)p1 females. P elementagging was used to clone the mutant allele, mod(r)p1. Subsequently, 28 kb of genomic DNA encompassing the wild-type mod(r) gene in the chromosomal region 1B was cloned. mod(r) encodes a 1.3 kb transcript which is not detected in the mod(r)p1 mutant. The sequences of mod(r) cDNA clones reveal that the gene encodes a protein of 200 amino acids in length. When compared to sequences in GenBank, the amino acid sequence did not reveal any long sequences similarities. However, the structure of the protein reveals similarities to known transcription factors. The N-terminal half of the protein is very acidic, whereas the C-terminal half is basic. The basic domain suggests a possible DNA-binding domain, while the acidic domain suggests a transcriptional activation domain. Consistent with this possibility is the fact that mod(r) acts through the 5' control region of the rudimentary gene to control its expression.
Mol Gen Genet 1995 Jul 22
PMID:Modifier of rudimentary p1, mod(r)p1, a trans-acting regulatory mutation of rudimentary. 765 29

The levels of Coenzyme Q10 (CoQ10) were determined by HPLC in seminal fluid samples obtained from 77 patients who performed a standard semen analysis for infertility, previous phlogosis or varicocele. CoQ10 was determined in total seminal fluid (n = 60), in seminal plasma (n = 44) and in the cell pellet (n = 37). The molecule, in total fluid, showed a linear correlation with sperm count and motility. In the pellet of spermatozoa, a trend toward an inverse correlation between CoQ10 (expressed as ng/10(6) cells) and semen parameters could be observed. A different pattern was shown in varicocele patients, in whom, in total fluid, the correlation between CoQ10 and sperm count was preserved, but the one between CoQ10 and sperm motility was lacking; moreover, a higher proportion of CoQ10 was present in seminal plasma, and the inverse trend between cellular CoQ10 and sperm count and motility was not observed. These data suggest a pathophysiological role of ubiquinone in human seminal fluid and a molecular defect in the spermatozoa of varicocele patients.
Mol Aspects Med 1994
PMID:Coenzyme Q10 levels in human seminal fluid: diagnostic and clinical implications. 775 37

The treatment of male factor-related infertility has been approached with the advent of several methods for microsurgical fertilization, such as the partial dissection of the zona pellucida (PZD) and the injection of sperm into the perivitelline space (PVSI) of oocytes. These techniques are designed to increase sperm-oolemma interaction by circumventing passage of the sperm through the zona pellucida. The present study was performed to evaluate the influence of PZD and PVSI on the in vitro development of mouse embryos by assessing the rate of sister chromatid exchange (SCE). SCE is considered to be a sensitive indirect indicator of DNA lesions due to various conditions. Oocytes were cultured in vitro after PZD or PVSI and then examined for SCE. There was no significant difference in SCE between control and treatment groups of embryos and the values were similar to those reported by Saito et al. (Fertil Steril 41:460-464, 1984). The rate of SCE was low during the first two mitotic cycles, then increased from cycle two to three before declining slightly between the 3rd and 4th cycles of cell division. These data demonstrate that the direct interaction of sperm and oocyte by PZD or PVSI did not have an adverse effect on the development of mouse embryos as assessed by the rate of SCE.
Mol Reprod Dev 1994 Jun
PMID:Assessment of sister chromatid exchange in mouse embryos produced by microsurgical fertilization. 808 Jun 42

Male mice homozygous for the azh mutation produce spermatozoa with abnormal head shapes and have significantly reduced fecundity, to between 5% and 10% that of wild-type or heterozygous mice. Several possible causes of this infertility were investigated. No gross endocrine disorders in azh/azh male mice were observed, and they exhibited apparently normal mating behavior. In addition, their sperm were motile, were capable of hyperactivated motility, and did not show premature acrosome reactions. However, quantitative analysis revealed slight but significant reductions in several motility parameters. Analysis of embryos following mating of azh/azh males with superovulated females indicated a reduction in the number of fertilized eggs compared to control matings. In vitro, spermatozoa from azh/azh mice failed to fertilize cumulus-intact/zona-intact and cumulus-free/zona-intact ova, although they successfully fertilized zona-free ova. These results indicate that the primary defect in fertility of azh/azh male mice is a result of sperm quality, likely, in sperm morphology, and is manifest at the level of interaction with the zona pellucida.
Mol Reprod Dev 1994 Jan
PMID:Deficiency in fertilization by morphologically abnormal sperm produced by azh mutant mice. 812 33

The androgen receptor belongs to the family of steroid-thyroid hormone-retinoid nuclear receptors. It contains 3 major domains: a hormone-binding region, a DNA-binding region and an amino-terminal region. Cloning of the cDNA encoding the androgen receptor and elucidation of the androgen receptor gene structure enabled the characterization of the molecular defects associated with androgen insensitivity. Mutations of the androgen receptor in 46,XY individuals cause a spectrum of androgen insensitivity syndromes, ranging from female phenotype (testicular feminization) to minor degrees of undervirilization or infertility. Reports on androgen receptor gene structure in patients with complete or partial forms of androgen insensitivity demonstrate that gene deletions are very rare. Several categories of mutations have been reported and are reviewed in this paper. Nucleotide substitutions in the androgen-binding domain or the N-terminal region that cause insertion of premature termination codons result in failure to form a functional protein. Missense mutations within the androgen-binding domain are responsible for a decrease or absence of receptor-binding activity. Mutations within the DNA-binding domain are associated with a positive receptor-binding form of androgen insensitivity. Analysis of described mutations indicates that they are spread throughout the gene, either associated with partial or complete androgen insensitivity. Furthermore, the same point mutation was reported to be associated with variable phenotypic expression of androgen insensitivity syndrome. It is thus difficult to define a genotype/phenotype relationship. However, mutations causing androgen insensitivity will certainly yield important new insights into the molecular basis of androgen action.
J Steroid Biochem Mol Biol 1993 Nov
PMID:Mutations of androgen receptor gene in androgen insensitivity syndromes. 824 Sep 73

The objective of this prospective study was to evaluate the specificity of human sperm/zona pellucida interaction under hemizona assay (HZA) conditions in experiments with gametes from the same and different species. Human, cynomolgus monkey and hamster oocytes were used after salt-storage. Oocytes were bisected into matching hemizonae by micromanipulation and used in the HZA. Semen was obtained from healthy men (donors) and male cynomolgus monkeys and prepared by wash and swim-up. Sperm binding to matching hemizonae was assessed (tight binding) after 4-h coincubation in the HZA in homologous and interspecies experiments. Acrosome reaction was evaluated in the sperm droplets using FITC-PSA and on the hemizonae using the T-6 monoclonal antibody. On human hemizonae, the number of tightly bound sperm for human and monkey were 93.2 +/- 15.8 and 3.9 +/- 1.3, respectively (P < 0.001). On monkey hemizonae, the number of tightly bound sperm for monkey and human were 126.0 +/- 34.8 and 2.8 +/- 1.6, (P = 0.02) respectively. On hamster hemizonae, there was negligible binding of human and monkey sperm. There was a significantly higher incidence of acrosome reacted sperm on the zona pellucida in homologous compared to heterologous experiments. These results demonstrate a high species-specificity of human gamete functions under HZA conditions, providing further support for the use of this bioassay in infertility and contraception testing.
Mol Reprod Dev 1993 May
PMID:The specificity of human spermatozoa/zona pellucida interaction under hemizona assay conditions. 850 81

Peri-fertilization exposure to Carbendazim (MBC; a microtubule poison) induces infertility and early pregnancy loss in hamsters. Presently, both in vivo and in vitro techniques were employed to characterize the effects of MBC on cellular aspects of fertilization in hamsters. Exposure to MBC during either in vivo or in vitro fertilization (IVF) induced identical morphological abnormalities in the maternal chromatin of zygotes and embryos. These abnormalities included either multiple second polar bodies (PB2), and/or multiple small female pronuclei (PN), or meiotic arrest. Multiple PB2, multiple female PN, multiple PB2 with multiple female PN, or meiotic arrest were exhibited by approximately 31%, 15%, 12%, and 2% of the in vivo zygotes; and 3%, 16%, 36%, and 20% of IVF zygotes, respectively. The effects of MBC persisted to day 2 of pregnancy as indicated by decreased (P < 0.05) embryo development to the two-cell stage and the presence of micronuclei in 6% of two-cell embryos from MBC-treated females. Immunofluorescence analysis of microtubules (MTs) confirmed that MBC disrupted spindle MTs during IVF. Numerical chromosome analysis revealed that a single dose of MBC administered during in vivo fertilization induced aneuploidy in the resulting pronuclear-stage zygotes. The present data point to two mechanisms by which peri-fertilization MBC exposure may induce early pregnancy loss: 1) arrested meiosis with no zygotic cleavage; or 2) induction of zygotic aneuploidy with subsequent developmental arrest.
Mol Reprod Dev 1995 Oct
PMID:Carbendazim (MBC) disrupts oocyte spindle function and induces aneuploidy in hamsters exposed during fertilization (meiosis II). 856 65

We tested the hypothesis that binding of rabbit isoimmune antisperm Fab fragments to rabbit sperm prior to artificial insemination could protect the sperm from isoimmune attack in vivo and lead to normal pregnancy and healthy offspring in isoimmune does. Twenty-four female rabbits and 4 males were used. Twelve does were immunized with rabbit sperm to induce isoimmunity and 12 does immunized with adjuvant/saline served as controls. Following 5 immunizations, the immune serum IgG fraction and its Fab fragments were prepared. The does from the control group and isoimmune group were artificially inseminated following the 6th and 7th immunization with untreated sperm or sperm pretreated with antisperm IgG or Fab in quadruplicates and allowed to complete a pregnancy. Three fertility trials were performed to investigate the therapeutic efficacy of Fab-coated sperm to restore fertility in isoimmune does. In the 3 fertility trials, none of the isoimmune does inseminated with untreated sperm had a successful pregnancy. By contrast, in 3 cases, rabbit sperm pretreated with antisperm Fab were able to fertilize in vivo with successful pregnancy in a control and isoimmune doe resulting in normal offspring. These results demonstrate that in vitro treatment of sperm with antisperm Fab fragments had a protective effect from isoimmune attack in vivo. The successful use of Fab fragments for reversal of antisperm antibody-mediated infertility observed in the isoimmune rabbit model offers the prospect of a new means of restoring fertility in some isoimmune women.
Res Commun Mol Pathol Pharmacol 1995 Jun
PMID:Protection of sperm from isoimmune attack in vivo by pretreatment with antisperm Fab: fertility trials in the immune rabbit model. 856 83

Fertilin (PH-30) is a sperm surface protein that functions in sperm adhesion and fusion with the egg plasma membrane. Because of its essential function in fertilization, fertilin is a potential target for novel contraceptive approaches. In a pilot fertility trial, immunization of male guinea pigs with purified guinea pig fertilin resulted in complete infertility. The contraceptive effect was partial (two out of six animals were infertile) when female guinea pigs were immunized with the antigen. These results suggest that fertilin or domains of fertilin may be effective as immunocontraceptive antigens. As a step toward achieving this goal, we communicate the cDNA and deduced amino acid sequence of the monkey fertilin beta subunit.
Mol Reprod Dev 1996 Jan
PMID:Initial evaluation of fertilin as an immunocontraceptive antigen and molecular cloning of the cynomolgus monkey fertilin beta subunit. 872 Jan 15

Genetic diseases presenting with different phenotypes are generally classified as distinct disorders before their molecular defect is revealed, as exemplified by the recent advance in understanding of the molecular biology of cystic fibrosis and an obstructive form of infertility, known as congenital absence of the vas deferens. The majority of men with congenital absence of the vas deferens have a defect in both copies of the CFTR gene and therefore represent a distinct phenotypic form of cystic fibrosis. These developments help us to gain new insight into the genetic basis of phenotypic variability and the possible contributing mechanisms in cystic fibrosis. Some of the lessons learned from the relationship between cystic fibrosis and congenital absence of the vas deferens may be useful in the understanding of other genetic disorders.
Mol Med Today 1996 Jan
PMID:Congenital absence of the vas deferens: a mild form of cystic fibrosis. 879 48


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