Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antisperm antibodies have been found in about 8% of men with infertility and in 60 to 80% of patients following vasectomy. In order to investigate the way antibodies influence sperm function we studied serum and seminal plasma from patients with infertility (n = 61) or undergoing vasovasostomy (n = 25). These antisera were characterised to determine their TAT titre, the nature of the target antigens and their capacity to interfere directly with fertilisation. The results indicate that antibodies from both groups of patients exhibit a capacity to stimulate or suppress sperm/oocyte fusion. The proportion of samples showing stimulatory activity was higher (50%) in the vasovasostomised population than in patients with infertility (21%). The remainder of the antisera suppressed sperm/oocyte fusion. There was no correlation between the titre of antisperm antibodies and their capacity to influence sperm function, indicating that it is the nature of the target antigens which is of significance rather than the antibody concentration. Western blot analysis indicated that these antisera targeted a group of sperm surface antigens with molecular weights of 30kD (35,45,66,90 and 115kD). Monoclonal antibodies are now being prepared in order to determine which of these specific components are involved in the suppression of sperm function.
 ...
PMID:Influence of antisperm antibodies on human sperm function. 319 63

In 94 infertile couples with negative postcoital tests (PCTs) the results of an in-vitro sperm-mucus invasion test (SMIT) were compared with seminal analysis (excluding sperm density less than 1 x 10(6)/ml) and agglutination assays for antisperm antibodies in semen (MAR, TAT) and in mucus (TAT). Abnormalities at the sperm-mucus interface were classed into three types. (i) Failure to form semen clefts and of spermatozoa to colonize the clefts was closely correlated with oligo-asthenoteratozoospermia, and vice versa, the two tests agreeing in 90% of cases (P less than 0.001). Most of the discrepancies, in which sperm-dense clefts developed despite low sperm counts, were due to antisperm antibodies in semen. (ii) Failure of spermatozoa to invade mucus, despite normal sperm colonization of clefts, was closely correlated with the presence of antisperm antibodies in semen (positive MAR or TAT), and vice versa, the tests agreeing in 81% of cases (P less than 0.001). (iii) Failure of sperm survival after normal invasion of mucus could not be correlated significantly with the TAT results on mucus, but more extensive study of this question is needed. Finally a normal SMIT result was associated with a significantly improved chance of conception (39 versus 10% at 12 months), particularly with artificial insemination, suggesting undisclosed coital failure as the cause of the negative PCT. In conclusion, the invasion test, when assessed in the foregoing detail, offers a reliable and simple substitute for laboratory assessment of both seminal quality and the presence of antisperm antibodies in semen, and would be applicable in general infertility practice everywhere.
 ...
PMID:The sperm-mucus interface: patterns of disorder in the diagnosis of specific causes of penetration failure causing infertility. 343 46

There are several antigens of the human sperm cell that can stimulate production of autoantibodies in certain individuals. This occurs in a number of spontaneous cases and leads to a condition of immunological infertility. It also occurs in a majority of men who have had a vasectomy. There are currently many new developments for the detection of the antibody, the study of its significance, and in the treatment of this autoimmune disease. As for the diagnostic testing of the serum, there are the classical methods of agglutination, namely, GAT, TSAT, TAT, and CTAT, and of immobilization. There are also the newer methods of the passive hemagglutination assay, the radio-label-antiglobulin test, the ELISA, the hemadsorption procedure, and the ATP-luminescence cytotoxicity method, plus indirect MAR (mixed antiglobulin reaction) and IBT (immunobead test) procedures. For testing of the genital secretions, sperm cells can be evaluated directly by the MAR and IBT methods, and cervical mucus, after being dissolved, can be tested by the MIS (microscale method) or an indirect IBT procedure. Interpretations of the significance of sperm antibody have been passed on epidemiologic values and also on direct fertilization-inhibition studies. Treatment of the antibody problem has been based on several approaches, but the most promising approach has been the use of intermittent high-dose steroid medication. A number of studies have shown good results by this procedure of immunosuppression.
 ...
PMID:Sperm antigens and autoantibodies: effects on fertility. 371 76

Serum antisperm antibodies were analyzed for 698 human couples with primary or secondary infertility to evaluate the incidence of antisperm antibodies in the circulation of men and women and in the cervical mucus of women as well as to evaluate the association of these antibodies with sperm penetration of cervical mucus in vitro and the relationship of these factors with subsequent fertility. Questionnaires concerning fertility status were mailed to 520 couples that had been analyzed for sperm antibodies from 1-3 years earlier. Completed questionnaires were obtained from 402 couples, and 376 of these couples were suitable for inclusion in the study. The mean duration of infertility was 4.1 +or- 2.5 years, with a range of 1-15 years for all couples; for 31 couples with secondary infertility, the duration was 3.4 +or- 1.9 years, with a range of 1.5-5.5 years. 14.8% of the men 19.6% of the women had sperm-agglutinating antibodies. An examination of the type of agglutination indicated that 88% of the positive sera showed the tail-to-tail type and the remainder showed the head-to-head type. The overall incidences of immobilizing antibody were 5.6 for men and 6.4% for women. The incidence of immobilizing antibody increased significantly in both men and women with increasing agglutination titers, as reflected by the respective correlations of 0.50 and 0.34 between the 2 tests. The incidence of pregnancy was influenced significantly by the presence of circulating sperm-agglutinating and immobilizing antibodies in both sexes. Sperm-immobilizing activity was detected in 29.6% of the cervical mucus samples from 459 women. The frequency of immobilizing antibody activity was significantly greater in samples from women with positive serum samples by either the TAT or the SIT. Sperm penetration of cervical mucus was significantly affected by the presence of either type of serum antisperm antibody in men and by sperm agglutinins in women. The incidence of subsequent pregnancy among the couples was significantly associated with each of the techniques utilized to assess antisperm antibodies. The sperm shaking phenomenon showed a significant effect that was most dramatic in those couples with more than 75% of the motile sperm exhibiting shaking in which only 1 of 13 experienced a diagnosed pregnancy. Significant but low correlation coefficients were found for the occurrence of pregnancy with the results of the serum and cervical mucus techniques. Multiple partial correlation analyses of the variables with pregnancy occurrence revealed that of the serum tests, agglutinating titers had significantly greater coefficients for men and women.
 ...
PMID:The incidence and influence of antisperm antibodies in infertile human couples on sperm-cervical mucus interactions and subsequent fertility. 711 71

Immunological infertility is thought to be caused by the binding of antibodies to 'fertility-related' antigen(s) on the sperm membrane. We compared antibody profiles in sera from 20 ASA(+) and ASA(-) men, using a sperm membrane extract as an antigen. Antigens were separated by SDS-PAGE under reducing conditions. The patients were classed as ASA(+) by the MAR (> 50%), d-IBT (> 20%) and TAT (> 1:64). The results showed that immunoreactive bands in both the ASA(+) and ASA(-) groups were heterogeneous and included bands covering the whole molecular weight range. Statistical analysis showed significantly more patients in the ASA(+) group having immunoreactive bands at molecular weights of 32 Kd (P = 0.006) and 79 Kd (P = 0.02) when compared to the ASA(-) group. In the ASA(-) group significantly more patients had reactive bands at 81 Kd (P = 0.01) when compared to the ASA(+) group. The 32 Kd antigen reacted only with sera from ASA(+) patients. We conclude that differences exist between the ASA(+) and ASA(-) groups when this extraction method is used and that the isolation and purification of the 32 Kd protein may justify further investigation.
 ...
PMID:Analysis of human sperm membrane antigens reacting with sera from antisperm antibody positive and negative patients by western blotting. 851 54

The presence of anti-sperm antibodies (ASAs) in seminal plasma is associated with infertility. They have been shown to reduce sperm motility, interfere with cervical mucus penetration and gamete interaction, and have been shown to reduce spontaneous fertilization and pregnancy rates. Although some causes can be determined, in the majority of cases the initial event causing the immune sensitisation and the reasons for the continuing antibody secretion remains unknown. Quantitative determination of total IgG, IgA and IgM within seminal plasma had not been previously reported in patients with and without specific ASAs. Semen samples from 512 men presenting with infertility were analyzed. One hundred and forty-six men (28.5%) had seminal fluid ASAs as determined by the MAR or TAT tests. The total seminal plasma IgG and IgA concentrations were significantly elevated in the ASA-positive groups compared with ASA-negative groups (IgG: 8.83 mg/100 ml vs. 7.15, P = 0.0008; and IgA: 2.88 mg/100 ml vs. 1.64, P = 0.0001). Only 19 samples showed seminal fluid IgM, and there was no difference between the ASA positive or ASA negative samples. The significance of these findings is discussed.
 ...
PMID:Seminal plasma immunoglobulin concentrations in autoimmune male subfertility. 957 71

No genes are yet directly implicated in etiology of male infertility. Identification of genes critical at various stages of spermatogenesis is pivotal for the timely diagnostic and treatment of infertility. We previously found that L-GILZ deficiency in a mouse KO model leads to hyperactivation of Ras signaling and increased proliferation in spermatogonia, resulting in male sterility. The possibility to establish culture cell system that maintains spermatogonial cells in vitro allowed us to delivery a recombinant protein TAT-L-GILZ able to restore normal proliferation rate in gilz KO spermatogonia. We also found that N-terminal part of L-GILZ protein is responsible for Ras/L-GILZ protein-to-protein interaction, important for the control of proliferation rate of spermatogonia. Therefore, treatments increasing L-GILZ expression, such as delivering small molecules or peptides that mimic L-GILZ functions, are approaches with great potential of applicability for new therapeutic strategies based on gene/protein delivery to the affected testes.
...
PMID:Recombinant long-glucocorticoid-induced leucine zipper (L-GILZ) protein restores the control of proliferation in gilz KO spermatogonia. 2499 77