胎盘滋养层合体化必需分子syncytin单核苷酸多态性对基因转录和蛋白质功能的影响及与妊娠结局相关性的研究

项目名称： 胎盘滋养层合体化必需分子syncytin单核苷酸多态性对基因转录和蛋白质功能的影响及与妊娠结局相关性的研究

项目编号： No.31271603

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 林海燕

作者单位： 中国科学院动物研究所

项目金额： 80万元

中文摘要： 胎盘绒毛合体滋养层由细胞滋养层细胞融合形成，分泌人绒毛膜促性腺激素和孕酮等激素，对于正常妊娠的建立和维持至关重要。合体化异常能引起子痫前期和习惯性流产等妊娠疾病。Syncytin是迄今发现的唯一的胎盘滋养层合体化的必需分子(fusogen)，其表达直接介导细胞融合。目前已发现syncytin-1和-2启动子和编码区的数十种单核苷酸多态性(SNP)，其中很多SNP位于启动子转录因子结合元件或蛋白质重要功能结构域中。然而，迄今没有报道表明这些SNP是否影响syncytin的基因转录、fusogen功能及胎盘合体化。本项目拟利用妊娠标本库和多种滋养层合体化模型，以搭建好的SNP鉴定、转录调控分析、体外蛋白质功能检测平台，研究影响syncytin转录和蛋白质功能的SNP与妊娠结局的相关性，以阐明胎盘滋养层合体化的分子机制，为揭示妊娠疾病胎盘发育障碍的机制及临床早期诊断和干预治疗提供重要的理论依据。

中文关键词： syncytin；胎盘；单核苷酸多态性；细胞融合；子痫前期

英文摘要： Placental syncytiotrophoblast, which is formed by cell-cell fusion of cytotrophoblast cells and secretes human chorionic gonadotropin and progesterone, is indispensable for the establishment and maintenance of normal pregnancy. Dysregulation in syncytialization leads to gestational diseases such as pre-eclampsia and habitual abortion. To date, syncytin-1 and -2 are the only genuine placenta-specific fusogens that have been discovered, whose expression can induce fusion of nonfusogenic cells. In the promoter and coding sequences of syncytin-1 and -2, dozens of single nucleotide polymorphisms (SNPs) have been released from public SNP database, and some of these SNPs are located within transcription factor binding sites of the promoter or important functional motifs of syncytins. However, whether these SNPs affect gene transcription/fusogenic function of syncytins and placental syncytialization remains unelucidated. Utilizing pregnancy-related clinical samples, multiple placental syncytialization models and research platform of SNP identification, transcriptional regulation and in vitro fusion assays, we sets out to investigate the linkage of SNPs, which affect gene transcription and fusogenic function of syncytins, to pregnancy outcome. We aim to elucidate the molecular mechanism of syncytialization and pathologic

英文关键词： syncytin；placenta；single-nucleotide polymorphism；cell-cell fusion；pre-eclampsia