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Query: UMLS:C0021359 (infertility)
 26,075 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sperm samples were collected from male partners of fertile and infertile couples having unexplained and male factor infertility and analyzed for morphological abnormalities. After a staining procedure, sperm samples of these infertile men showed a variety of abnormalities. The sperm samples were also studied for their binding with the Abs directed against protamine (the nuclear protein), fertilization antigen (FA-1, sperm surface antigen), and the lithium diiodosalicylate- (LIS-) solubilized sperm preparation, and the binding was correlated with the percentage of morphologically abnormal sperm in the sample. Abs used in the present study were raised in female rabbits and had high titers (ELISA titers, 1:4096 to 1:8196), and recognized no band (anti-protamine), one 49,000- +/- 2000-dalton band (anti-FA-1), and at least 8 bands of various molecular identities in the 14,000- to 92,000-dalton range (anti-LIS sperm) on the Western blot of LIS-solubilized human sperm. The affinity-purified Fab' antibodies were iodinated and used in a radioimmunobindingassay for testing their binding with the sperm cells. Anti-protamine Fab's showed minimal binding and the binding activity (cpm bound/10 x 10(6) sperm cells) did not correlate (head defect, r = .12; midpiece defect, r = .07; tail defect, r = .11) significantly with percentage of abnormal cells in the sample. The binding of the anti-FA-1 Fab's also did not show a significant correlation (head defect, r = .29; midpiece defect, r = .48; tail defect, r = .23), though a positive trend (p = .05) was observed with the midpiece defect. In contrast, the binding of anti-LIS sperm Fab's demonstrated a significant correlation with the percentage of abnormal sperm cells in the sample (head defect, r = .51, p = .04; midpiece defect, r = .80, p less than .0001; tail defect, r = .23, p = .039). With an increased percentage of abnormal sperm cells, especially those with midpiece defect, there was an increased binding of anti-LIS sperm Fab's. These results suggest that with an increase in percentage of abnormal sperm, there is a change in antigenicity of the sperm cells. An increase in structural abnormality may enhance antibody binding to an abnormal sperm cell, thus causing a further decrease in its fertilizing capacity.
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PMID:Antigenic differences in human sperm samples related to various morphological abnormalities. 145 33

A review of the obstacles in the way of producing anti-sperm contraception and progress to date is presented. While there are several lines of evidence pointing to the possibility of inducing immunity to sperm, in practice many roadblocks have appeared such as sperm antigens that cross react with other somatic antigens, effective sperm antigens that do not affect fertility, short acting immunity, and the problems of producing high titers in the local environment of the genital tract. Infertility of both men and women occurs in nature as a result of antisperm immunity. Conception can be obtained in these couples by immunosuppression. Data from human in vitro fertilization indicate that sperm antibodies can block fertilization. since whole sperm contain several antigens shared with other body tissues, a vaccine must be designed from purified antigens. After vaccines were developed from some antigens, such as HS-63, in vitro fertilization was blocked but not fertility in vivo. One antigen showing promise is FA-1 from human and mouse sperm, effective in reducing rabbit and human fertility. All the prototype vaccines have a short life time. Adjuvants and carriers are being tested to improve performance. The female genital tract is not rich in lymph tissue, but IgG and sigA antibodies do occur there, probably originating from gut-associated lymphoid tissue. Not only is a very high titer of antibodies needed to block fertilization in vivo, but local immunization is ineffective in inducing high titers. Probably combined local and systemic routes will be required.
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PMID:Development of antisperm contraceptive vaccine for humans: why and how? 220 2

Sera (n = 19) from immunoinfertile patients were analyzed for cross-reaction with lithium diiodosalicylate (LIS)-solubilized human sperm extract (HSE), protamine and fertilization antigen (FA-1) using an enzyme-linked immunosorbent assay (ELISA). Among the sera tested, 63% reacted with HSE, 58% with protamine and 63% with FA-1. None of the sera from male or female infertile patients was found to contain immune complexes, indicating the antibodies were present in free form. The seven sera that reacted strongest with HSE inhibited human sperm function in sperm penetration of zona-free hamster ova and were associated with fertilization failure in human in vitro fertilization (IVF) technique. The six of these sera that showed binding to rabbit sperm, especially in the head region, also inhibited fertility in female rabbits. Antibodies reactive with FA-1 and not those reactive with protamine reduced fertility in female rabbits. These results indicate that mammalian sperm have several fertilization-related antigens that are evolutionarily conserved. These data also indicate that the rabbit can provide an animal model for studying antibody-mediated human infertility.
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PMID:Effects of sperm-reactive antibodies present in human infertile sera on fertility of female rabbits. 225 79

Sperm antigens were assessed for their ability to induce cell-mediated immune (CMI) responses. Purified fertilization antigen (FA-1), protamine, and the lithium diiodosalicylate (LIS)-solubilized sperm preparation activated presensitized lymphocytes to secrete soluble mediators that activated macrophages and significantly inhibited sperm motility and embryonic development. The FA-1, however, was the most potent antigen in inducing proliferative response as well as the release of soluble mediators. LIS-sperm preparation, which contained numerous antigens, showed the least activity. The unsensitized control spleen cells did not secrete any factor(s) when activated with the antigen. In conclusion, these results indicate that sperm antigens can specifically induce (CMI) factors that have detrimental effects on sperm motility and preimplantation embryos. These findings may have potential clinical implications for humans, especially in immunologic and unexplained infertility, recurrent abortions, and development of antisperm contraceptive vaccines.
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PMID:Cell-mediated immune responses to sperm antigens: effects on mouse sperm and embryos. 259 Jul 18

Sera (vbs, n = 25) and seminal plasma (vsp, n = 21) from vasectomized men (n = 25) were analyzed for cross-reaction with lithium diiodosalicylate (LIS)-solubilized human sperm extract, protamine, and fertilization antigen (FA-1) with an enzyme-linked immunosorbent assay (ELISA). Among the vbs tested, 44% reacted with human sperm extract, 28% reacted with protamine, and 44% reacted with FA-1 for at least one class of antibodies (IgG, IgA, or IgM). In contrast to the sera, the seminal plasma showed minimal reactions. Neither the vbs nor vsp were found to contain immune complexes, indicating that the antibodies were present in free form. Vasectomized sera that reacted with FA-1 showed a significant (p less than 0.0001) inhibition of human sperm penetration of zona-free hamster ova. The immunoabsorption of FA-1-positive sera with purified FA-1 significantly increased the penetration rates. Affinity-purified human immunoglobulins reactive with FA-1 and not those reactive with protamine reduced sperm penetration rates. Thus, antibodies in vbs reactive with FA-1 are relevant to infertility, causing an inhibition of fertilization. These data will have clinical relevance for diagnosis and treatment of infertility after successful vasovasostomy.
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PMID:Sperm antibodies in vasectomized men and their effects on fertilization. 280 5

Fertilization antigen (FA-1), the ideal antigen for the development of an antisperm contraceptive vaccine, should be involved in the fertilization process rather than embryonic development. FA-1 has been obtained through the use of a sperm-specific but species-cross reactive monoclonal antibody (MA-24) raised against human spermatozoa. Female rabbits were chosen to study the effects of active immunization because the monoclonal antibody to FA-1 (MA-24) reacted with rabbit sperm and caused reduction in fertilization in female rabbits in passive immunization experiments. A significant reduction in fertility occurred after immunization with FA-1. The data indicate that the active immunization with FA-1 results in a tissue-specific immune response that causes a reduction of fertility in rabbits by a mechanism(s) involving an inhibition of the fertilization process. FA-1 appears at this time to be promising for the development of an antisperm contraceptive vaccine and for the diagnosis and treatment of infertility in humans mediated through antisperm antibodies.
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PMID:The fertilization antigen (FA-1): applications in immunocontraception and infertility in humans. 328 7

The present study was conducted to investigate the molecular identities, nature of interaction, and tyrosine phosphorylation activity of the sperm-zona pellucida binding proteins in humans. Sperm proteins belonging to four major molecular regions, namely 95, 63, 51, and 14-18 kDa, reacted with zona pellucida proteins in the Western blot and immunoprecipitation procedures. In these procedures, zona pellucida protein that reacted strongest with the sperm proteins belonged to the molecular region of 55 kDa (ZP3), besides weakly reacting proteins in the 110-kDa (ZP1/ZP2) and 14-18-kDa molecular regions. The major forces involved in the sperm-zona protein interactions were of hydrophobic and ionic in nature. Three (95, 51, and 14-18 kDa) of the four molecular regions of sperm proteins that bound to the zona pellucida proteins also seem to involve o-phospho-L-tyrosine residues in their interaction, and these proteins demonstrated the presence of phosphotyrosine residues, and the 51-kDa protein also showed autophosphorylating activity in the in vitro kinase assay. The sperm binding zona protein of 55 kDa also demonstrated autophosphorylating activity. Using specific monoclonal antibody to the well characterized sperm-specific glycoprotein, designated FA-1, and the competitive inhibition in the immunoprecipitation procedure, it was found that the 51 kDa protein is indeed FA-1 antigen. Besides elucidating the molecular nature of the sperm-zona interaction, these antigens will find application in the development of a multivalent contraceptive vaccine, and may also help in specific diagnosis and treatment of infertility mediated through defective gamete (sperm or oocyte) function.
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PMID:Molecular identities of human sperm proteins that bind human zona pellucida: nature of sperm-zona interaction, tyrosine kinase activity, and involvement of FA-1. 753 65

Immunoinfertility is an important problem, involving a significant number of infertile couples. Although the presence of antibodies on sperm has better prognostic value than those in serum or seminal plasma, it may not be the sole authentic evidence of immunoinfertility. Infertility from antisperm antibodies is likely only when they bind to a relevant sperm antigen involved in a specific fertility function. The variance in functional deficits seen in immunologic infertility is most likely related to antibodies directed at different sperm antigens or different class, subclass, or isotypes. Antibodies to FA-1 seem to be of significant importance in human immunoinfertility. In approaching couples with infertility, a high index of suspicion for antibodies is necessary to avoid misdiagnosis. In the optimal situation, all semen analyses should be screened for sperm-bound antibodies, but if this is impractical, testing should be performed on high-risk individuals (Table I). In couples in which the man has sperm-bound antibodies, and in whom there is no identifiable female factor, treatment should be instituted. Most treatments for immunoinfertility have been disappointing because of poor results, adverse effects, or high cost. Corticosteroid therapy has shown some promise in published reports (mostly poorly designed studies), but increase in pregnancy rate is modest and adverse effects may be significant. In our opinion, informed consent should be documented prior to institution of corticosteroid therapy, and subjects should be closely monitored. Advanced reproductive technologies offer a higher safety profile, and, with increasing technology, higher pregnancy rates. We recommend progressing from "low-tech" procedures, such as IUI and reserving the higher level procedures, such as IVF and ICSI, for those couples in whom pregnancy does not occur. The highest level reproductive technologies give the best current prospects for pregnancy in patients with this difficult problem but also are invasive and costly. It is hoped that further work in the laboratory will give rise to newer, safer, and less expensive effective treatments in the very near future.
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PMID:Infertility due to antisperm antibodies. 757 Dec 38

A fertilization antigen (FA-1) has been identified on human sperm cells that is involved in human fertilization. To better explain the participation of FA-1 in human infertility, the relationship of anti-FA-1 antibodies with the presence of general antisperm antibodies and with sperm function was examined in the sera of 30 men and women. None of the sera from fertile men and women (n = 10) reacted with FA-1. In contrast, 55% of the immunoinfertile sera (n = 20) that were positive for antisperm antibodies detected by OPTI-BEAD (immune-labeled microsphere) tested positive with FA-1 (p < .05). In these sera, penetration of hamster oocytes was reduced and was inversely related to monospecific anti-FA-1 absorbance values determined by an ELISA and with heterospecific general antisperm antibody binding to sperm in the OPTI-BEAD test (p < .05). Anti-FA-1 activity approached significance with antisperm antibody binding to the sperm head (p = .052). It is concluded that immunoinfertile sera have antibodies reacting with the FA-1 sperm antigen and their presence is significantly related to results of other functional tests, such as the SPA and the OPTI-BEAD test. The association of anti-FA-1 antibodies with antibody binding site (sperm head) may be relevant to the diagnosis and treatment of immunoinfertility.
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PMID:Significance of antibodies against human sperm FA-1 antigen in immunoinfertility. 812 33

Development of a vaccine(s) based on sperm antigens represents a promising approach to contraception. The utility of a sperm antigen in immunocontraception is contingent upon its tissue specificity, involvement in fertility and on raising high antibody titer, especially locally in the genital tract, that is capable of inducing reversible infertility. Several sperm antigens, such as lactate dehydrogenase C4, PH-20, sperm protein (SP)-10, fertilization antigen (FA)-1, FA-2, cleavage signal (CS)-1, NZ-1, and NZ-2 have been proposed as potential candidates for the vaccine development. Spermzona pellucida (ZP) binding is a pivotal tissue- and mostly species-specific event in the fertilization process, and the molecules involved in this site constitute the most exciting candidates for immuno-contraception. FA-1 is a sperm-specific glycoprotein having receptor activity for ZP recognition and binding. Complementary DNA encoding for FA-1 antigen has been cloned and sequenced. Active immunization of animals with recombinant FA-1 antigen causes a long-lasting reversible inhibition in fertility by raising a sperm-specific immune response. This antigen is also involved in human immunoinfertility. The exciting findings from the recent trial in immunoinfertile couples indicate that the FA-1 antigen may have clinical application in the treatment of male infertility. A vaccine having most appropriate tissue-specific and effective recombinant and/or synthetic epitopes of various sperm antigens, such as the FA-1 antigen, in a single formulation may provide a highly immunogenic and efficacious antisperm vaccine for contraception. The advances made during the last 5 years suggest that it may be a realistic proposition.
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PMID:Vaccine for contraception targeting sperm. 1058 72


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