凋亡相关调控基因在早期胚胎发育中作用机制的研究

项目名称： 凋亡相关调控基因在早期胚胎发育中作用机制的研究

项目编号： No.30872769

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 李红

作者单位： 南方医科大学

项目金额： 32万元

中文摘要： 细胞凋亡是着床前胚胎细胞死亡的主要方式，也是导致胚胎发育停滞和IVF-ET失败的主要原因。细胞凋亡的机制十分复杂，至今仍未完全明确。目前研究认为，抗凋亡分子和促凋亡分子在调节胚胎发育和胚胎细胞凋亡方面起关键性作用，其相互间的平衡决定胚胎细胞的命运。其中，Bcl-2家族和天冬氨酸特异性半胱氨酸蛋白酶（半胱天冬酶，Caspase）家族是早期胚胎中表达的两大主要细胞凋亡调控基因。抗凋亡人工干预胚胎措施可能成为促进早期胚胎发育、提高胚胎质量和IVF成功率的新途径。本课题拟以小鼠早期胚胎为研究对象，在体外胚胎培养基中加入1-磷酸鞘氨醇（S1P）、Caspase广谱抑制剂（CAI）和干细胞因子（SCF），分析上述抗凋亡因子对胚胎早期发育的影响，探讨其对C2-神经酰胺（CED）或过氧化氢（H2O2）诱导胚胎细胞凋亡的抑制作用，并通过深入探讨1-磷酸鞘氨醇抑制CED在诱导小鼠早期胚胎细胞凋亡的可能机制，研究结果显示抗凋亡因子能够提高小鼠早期胚胎的质量，为将来建立一种有效稳定安全的多因素协同抗凋亡干预促胚胎发育方法并最终将其应用于人类辅助生殖技术上提供一定的理论和实验依据。

中文关键词： 细胞凋亡；抗凋亡因子；1-磷酸鞘氨醇；C2-神经氨酸；着床前胚胎

英文摘要： Apoptosis is the main form of cell death of preimplantation embryos, and it can cause arrest of embryonic development and failure of in vitro fertilization and embryo transfer(IVF-ET). The mechanism of molecular regulation of apoptosis may be very complicated and has not yet been clear. The current study suggested that both proapoptotic factors and antiapoptotic factors play important roles in regulating embryonic development and cell apoptosis, and that the balance of the two contrary factors determines the survival or death of embryonic cells. As we know,the members of Bcl-2 family and Caspases are the two main apoptotic regulary genes expressed in early embryos. Antiapoptotic artificial interfering technique may be a new approach of improving embryonic quality and promoting the successful rate of IVF-ET. Therefore, in this study we used mouse early embryos to evaluate the effects of antiapoptotic factors such as Sphingosine 1-phosphate(S1P), broad-spectrum Caspase inhibitor(CAI), stem cell factor(SCF) during mouse preimplantation embryonic development and to determine effective concentrations of these antiapoptotic factors, and to further investigate effects of them on suppressing apoptosis of early mouse embryos induced by C2-ceramide(CED) or hydrogen peroxide(H2O2). Furthermore,we detected the mechanism about the effects of S1P to decrease the apoptosis of embeyonic cells induced by CED. The results showed that antiapoptotic factors especially S1P can improve the quality of mouse early embryos.The results suggested that application of antiapoptotic artificial interfering technique is a feasible way to enhance the quality of embryos in human assisted reproductive technology(ART).

英文关键词： cell apoptosis; antiapoptotic factor;Sphingosine 1-phosphate;C2-ceramide;preimplantation embryo