The mechanism of pregnancy from the viewpoint of mutual control system of mother and embryo

从母体与胚胎相互控制系统看妊娠机制

基本信息

批准号：
11307031
负责人：
TAKETANI Yuji
金额：
$ 17.52万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

For the breakthrough of reproductive medicine, the comprehensive understanding on the implantation mechanism is indispensable. In this study, we focused on mutual control system of embryo and mother in the implantation phenomenon, and intended to grasp the dynamic mechanism of implantation polyphyletically.To begin with, we examined how the peripheral blood lymphocyte and the decidual lymphocyte in the implantation site respond to a membrane bound HLA- G antigen on the villus. It was demonstrated that the secretion of the Th1 cytokine is decreased when the peripheral blood lymphocyte recognizes HLA-G, while the secretion of the Th2 cytokine is increased. On the other hand, for the decidual lymphocyte, the secretion of the Th1 cytokine is stimulated by the contact with HLA-G, while the secretion of the Th2 cytokine does not change. The differential response between the peripheral blood lymphocyte and the decidual lymphocyte may be explained by the fact that the B cell exist in the perip … More heral blood but not in decidua, and the blocking antibody crucial for the maintenance of pregnancy can be produced only by the peripheral B cell.Next, we investigated the expression of angiogenin, the potent angiogenic substance, in the human ovaries and its regulatory mechanisms. Angiogenin was shown to be present in follicular fluid and granulosa cell obtained from the patient for in vitro fertilization and embryo transfer. In the granulosa cell culture, the secretion of angiogenin was stimulated 3 times by hCG or CAMP, 5.5 times by the hypoxia stimulation. The mRNA level of angiogenin was 12.5 times up regulated by the hypoxia stimulation.In addition, we attempted to elucidate the physiological roles of cholesterol sulfate, which increased in the uterine endometrium at the implantation period. As a result, it was shown that cholesterol sulfate inhibited the invasion of trophoblast into the endometrium, and the mechanism of the inhibition was non-competitive inhibition of the plasmin activity. Less

生殖医学的突破离不开对着床机制的全面认识，本研究重点关注胚胎与母体在着床现象中的相互控制系统，旨在从多系角度把握着床的动态机制。我们检查了植入部位的外周血淋巴细胞和蜕膜淋巴细胞如何响应绒毛上的膜结合HLA-G抗原，结果表明，当外周血淋巴细胞减少时，Th1细胞因子的分泌减少。识别HLA-G，而Th2细胞因子的分泌增加；另一方面，对于蜕膜淋巴细胞来说，与HLA-G接触会刺激Th1细胞因子的分泌，而Th2细胞因子的分泌则不会。外周血淋巴细胞和蜕膜淋巴细胞之间的差异反应可能是由于 B 细胞存在于围周血中而不是蜕膜中，而封闭抗体对于维持妊娠至关重要。只能由外周B细胞产生。接下来，我们研究了血管生成素（一种有效的血管生成物质）在人卵巢中的表达及其调节机制，结果表明血管生成素存在于从患者体内获得的卵泡液和颗粒细胞中。体外受精和颗粒胚胎移植在osa细胞培养中，hCG或CAMP刺激血管生成素的分泌3倍，缺氧刺激5.5倍。缺氧刺激下血管生成素的mRNA水平上调12.5倍。此外，我们试图阐明硫酸胆固醇的生理作用，硫酸胆固醇在着床期子宫内膜中增加。结果表明，硫酸胆固醇具有抑制作用。抑制滋养层细胞向子宫内膜的侵袭，其抑制机制为非竞争性抑制纤溶酶活性。