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アセトアルデヒド脱水素酵素群の基質選択性に着目した卵胞発育機構の分子内分泌的解析

以乙醛脱氢酶基团底物选择性为中心的卵泡发育机制的分子内分泌分析

基本信息

批准号：
13J02153
负责人：
川合智子
金额：
$ 1.15万
依托单位：
Hiroshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for JSPS Fellows
财政年份：
2013
资助国家：
日本
起止时间：
2013-04-01 至 2015-03-31
项目状态：
已结题

项目摘要

FSHが誘起し，排卵刺激を感受する排卵前卵胞形成に顆粒膜細胞のLH受容体(Lhcgr)発現が必須であるが，Lhcgrは排卵刺激(LHサージ)直前まで発現しない．Lhcgr発現は，FSHにより活性化される転写因子Sp1がプロモーター領域に結合することで誘起されるが，その時期をLHサージと同調させる仕組みは不明である．従って，この発現機構を解明することで，家畜繁殖異常で高い割合を占める卵胞発育障害の解明にも繋がると考えられた．本研究では，Lhcgr発現に必要な新規因子探索に遺伝子発現網羅解析を行い，レチノイン酸（RA）合成酵素を見出し，LHサージに同調した顆粒膜細胞のLhcgr発現機構の解明を試みた．RAとLhcgr発現の関係を調べるため，内因性RAに反応しLacZを発現するRARE-LacZ遺伝子導入マウスを用いた．FSH刺激を受けた顆粒膜細胞でLacZ陽性が認められ，同じ細胞にLhcgrも局在していた．LacZ活性は，RA合成の抑制剤により低下した．そこで，RA合成抑制剤を卵胞発育ホルモン（eCG）と同時投与するとLhcgr発現が有意に抑制され，排卵数，卵の成熟・発生能も低下した．しかし，Lhcgrプロモーター領域にRA応答配列がない．つまり，RAによるLhcgr発現制御は間接的と考え，Sp1結合サイトのCpG配列に着目し，DNAメチル化解析を行った．eCG投与前では CpG配列のメチル化割合は高いが，eCG投与によりその割合は著しく減少した．一方，eCGとRA合成抑制剤の同時投与はメチル化を維持していた．排卵前卵胞形成時には，Lhcgr以外にも多くの遺伝子で脱メチル化が起こっていることも見出している．引き続き詳細に検討し，RAが誘起する脱メチル化と共に核内の遺伝子発現基盤を解明することで，顆粒膜細胞の機能変化と卵の成熟・発生能の関係性が明らかになると期待している．

FSH pregnancy occurs, ovulation stimulation induces the formation of granulosa membrane cells before ovulation, LH receptive bodies (Lhcgr) must be detected, Lhcgr ovulation stimulation (LH stimulation) can be detected directly before ovulation, Lhcgr response is detected, and FSH activation response writing factor Sp1 response is activated by the combination of domain analysis and domain analysis. In this study, Lhcgr found that it is necessary to use new rule factors to explore the network analysis network, and to find out that it is necessary for Lhcgr to explore new regulation factors in this study. In this study, Lhcgr found that it is necessary to use new regulation factors to explore the network analysis network, and to detect the synthesis of enzymes in the production of fatty acid (RA) in livestock breeding. The mechanism of LH receptor homoplasmic membrane cytoskeleton Lhcgr showed that there was no significant difference between Ra and RA Lhcgr, while the internal cause of RA response LacZ showed that the receptor RARE-LacZ was activated. FSH stimulated the recipient granulosa membrane cell to induce LacZ response. Lacz activity was detected in the same cell Lhcgr. RA synthesis suppresses low energy levels, RA synthesis inhibits oocyte rearing cycle (eCG) simultaneously, and the number of ovulations, the number of ovulations, and the energy production of mature oocytes are significantly lower than those of the control group. The number of ovulations, the number of ovulations, and the energy production of mature oocytes are significantly lower than those of the control group. The results show that Lhcgr synthesis inhibits the growth of mature oocytes, the field of Lhcgr synthesis, the field of RA response, and the monitoring of RA responses. The combination of Sp1 and CpG was used to determine the target, and the DNA assay was used to analyze the target. ECG was coupled with the previous CpG to cut off the high temperature, and the eCG was cut off with the previous one. On the one hand, the inhibition of eCG RA synthesis was simultaneous with the maintenance of the cycle, and the formation of preovulatory oocytes was maintained. In addition to the Lhcgr, you need to know how to make a difference. In this way, you can learn how to do it. In addition, you need to know how to do it. In addition, you need to know that there is a lot of trouble in the whole nucleus. In addition to the Lhcgr, you can learn more about the problem that you need to know that there is a problem in the development of a mature egg.