MECHANISM OF IMMUNOLOGICAL INFERTILITY DUE TO THE 75kD HUMAN SPERM ANTIGEN AND ITS SIGNIFICANCE AS CONTRACEPTIVE VACCINE
75kD人类精子抗原导致免疫性不孕的机制及其作为避孕疫苗的意义
基本信息
- 批准号:06671656
- 负责人:
- 金额:$ 1.22万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for General Scientific Research (C)
- 财政年份:1994
- 资助国家:日本
- 起止时间:1994 至 1995
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Identification of the epitope recognized by antisperm antibodies is important to clarify for the mechanism of immunological infertility and development of immunocontraceptive vaccine. We are trying the active immunization of experimental animals with synthetic peptides fragments corresponding to the sperm specific antigens. Among them, two peptides, YAL-198 (YAL) and rSMP-230, cause infertility of female rats by active immunization. In this project, we synthesized new sperm antigen peptides originated from the deduced amino acid sequence of the 75kD human sperm antigen reacted antisperm antibody produced in the infertile women. Furthermore, we prepared antibodies to YAL,which is corresponding to the extracellular domain of a human sperm protein interacting monoclonal antibody (YWK-II) which induces agglutination of human and rat sperm, and elucidated the contraceptive mechanism by active immunization with YAL.1. Synthesis of the extracellular domain of the 75kD human sperm antigenTwo p … More eptide segments corresponding to the extracellular domain of the 75kD human sperm antigen were synthesized by Fmoc solid phase method. The peptides that composed of 16 residue amino acids were yielded 17mg and 15mg. Amino acid analysis showed that the composition corresponds to the theoretical ratio.2. Effects of anti-YAL antibodies on fertilization and embryo development.(1) Rabbit polyclonal and murine monoclonal antibodies (pAb and mAb) were prepared as described previously, and IgG fraction was separated by Protein G column chromatography. The pAb and mAb caused neither agglutination nor immobilization of human spermatozoa. Furthermore, hamster test was not inhibited following exposure of human sperm to anti-YAL antibodies.(2) We examined the effects of antibodies to YAL on fertilization and development of the fertilized eggs in murine model to elucidate the contraceptive mechanism of the active immunization with YAL.Fertilization rates were not different between in control group and in anti-YAL antibody group. However, the development to 4 cell stage embryo or morula was significantly (p<0.05) inhibited, when exposed to antibodies.These results suggest that active immunization of YAL causes infertility by impairment of embryo growth, but not by inhibition of fertilization, which is the main etiology of infertile women possessing antisperm antibodies. Less
抗精子抗体识别的抗原表位的鉴定对阐明免疫性不孕的机制和研制免疫避孕疫苗具有重要意义。我们正在尝试用合成的与精子特异性抗原相对应的肽片段对实验动物进行主动免疫。其中YAL-198 (YAL)和rSMP-230两种多肽通过主动免疫引起雌性大鼠不孕。在本项目中,我们从不育妇女产生的75kD人精子抗原反应抗精子抗体的氨基酸序列中推断合成了新的精子抗原肽。此外,我们制备了一种诱导人和大鼠精子凝集的人精子蛋白相互作用单克隆抗体(YWK-II)胞外结构域对应的YAL抗体,并通过YAL.1主动免疫阐明了其避孕机制。用Fmoc固相法合成了更多与75kD人精子抗原胞外结构域相对应的肽段。由16个残基氨基酸组成的肽得到17mg和15mg。氨基酸分析表明,其组成符合理论配比。抗yal抗体对受精和胚胎发育的影响。(1)按上述方法制备兔多克隆抗体和鼠单克隆抗体(pAb和mAb),用蛋白G柱层析分离IgG部分。pAb和mAb既不引起人精子的凝集也不引起人精子的固定。此外,仓鼠试验不受人类精子暴露于抗yal抗体后的抑制。(2)在小鼠模型上检测了YAL抗体对受精卵受精和发育的影响,以阐明YAL主动免疫的避孕机制。抗yal抗体组与对照组受精率无显著差异。然而,抗体对4细胞期胚或桑葚胚的发育有显著抑制作用(p<0.05)。这些结果表明,YAL的主动免疫通过损害胚胎生长而不是抑制受精导致不孕,这是不孕妇女具有抗精子抗体的主要原因。少
项目成果
期刊论文数量(44)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Hirano M.: "Significance of immunoglobulin binding factor as the sperm coating antigen" Proceedings of the 9th Annual Meeting of JSIR. 9. 25-26 (1995)
Hirano M.:“免疫球蛋白结合因子作为精子包被抗原的意义”,JSIR 第九届年会论文集。
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- 影响因子:0
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Hirano M.: "Significance of immunoglobulin binding factor as the sperm coating antigen." Proceedings of the 9th Annual Meeting of Japan Society for Immunology of Reproduction. 25-26 (1995)
Hirano M.:“免疫球蛋白结合因子作为精子包被抗原的意义。”
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- 影响因子:0
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Takikawa M.: "Complement inhibiting factor in human seminal plasma and semen analysis." Proceedings of the 9th Annual Meeting of Japan Society for Immunology of Reproduction. 21-22 (1995)
Takikawa M.:“人精浆和精液分析中的补体抑制因子。”
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- 影响因子:0
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Takikawa M.: "Complement inhibiting factor in human seminal plasma and semen analysis" Proceedings of the 9th Annual Meeting of JSIR. 9. 21-22 (1995)
Takikawa M.:“人精浆和精液分析中的补体抑制因子”JSIR 第九届年会论文集。
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- 影响因子:0
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Kamada M.: "Detection of immunoglobulin binding factor by enzyme-linked immunosorbent assay using two monoclonal antibodies" Biochem.Mol.Biol.Int.34. 837-844 (1994)
Kamada M.:“使用两种单克隆抗体通过酶联免疫吸附测定检测免疫球蛋白结合因子”Biochem.Mol.Biol.Int.34。
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MORI Hidetoshi其他文献
MORI Hidetoshi的其他文献
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{{ truncateString('MORI Hidetoshi', 18)}}的其他基金
Development of prevention technique for the silica scale deposition interfering with utility systems of geothermal energy
硅垢沉积干扰地热能利用系统防治技术开发
- 批准号:
14550735 - 财政年份:2002
- 资助金额:
$ 1.22万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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SEX RATION DISTORTION AND THE PH-20 SPERM ANTIGEN
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ISOLATION AND CHARACTERIZATION OF A NOVEL HUMAN SPERM ANTIGEN (H-SP-1)
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- 批准号:
06671697 - 财政年份:1994
- 资助金额:
$ 1.22万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
Production of human monoclona. antibody to spermatozoa and its application for purification of the corresponding sperm antigen.
人单克隆抗体的生产。
- 批准号:
61570815 - 财政年份:1986
- 资助金额:
$ 1.22万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)