未成熟卵母细胞体外培养对F2代小鼠脑组织基因表达影响、作用机理及隔代效应研究

未成熟卵母细胞体外培养(IVM)技术目前已经成为多囊卵巢综合症、卵巢反应不良和反复胚胎质量不良妇女不孕症治疗的重要手段，也是保存生殖能力及建立卵子库的重要方法。IVM包括了IVF-ET或ICSI的所有体外操作，并有长时间脱离卵巢内环境体外培养成熟的过程，受到额外的化学物理因素刺激，其影响将是全基因组水平的，引发的基因表达改变将会因某些通路激活或关闭、或不同基因之间的相互调节。目前七、八十年代出生的IVF儿已进入婚育期，ART对人类的影响和效应将开始跨代显现，但迄今为止，有关IVM跨代安全性的研究仍完全空白。本项目以小鼠为模式生物，拟以本课题业已开展的F1代IVM小鼠脑组织全基因表达谱研究为基础，分析IVM过程对F2代小鼠基因表达变化的影响，进行IVM小鼠F2代脑组织相关基因表达及动态变化、调控机制以及相关组织形态和行为学变化研究，为ART神经系统跨代安全性提供依据。

IVM has now become an important means for treatment of female infertility , such as PCOS, repeated poor embryo quality, poor ovarian response, and as important means of preserving reproductive capacity and the establishment of the egg bank. IVM covering around all the in-vitro manipulations existed in the IVF-ET or ICSI, the oocytes are long periods away of in vitro maturing process from environments in the ovaries,and are subjected to additional stimulations orgined from chemical or physical factors. Therefore, we think the effects of IVM could be the whole genome level, and the changes of gene expression would vary based on certain pathways activated or closed, or between different genes mutual adjustment. Now IVF people born in the eighties have entered a period of marriage and childbirth, ART will begin cross-generational effects, but so far, the safety about IVM inter-generations is still completely blank. By establishing the IVM mice model, and with the foundation of the research about the whole genome expression in the F1 generation, our project will analyze the effects of IVM on gene expressions, their dynamic changes and regulation mechanism in mice brains of F2 generations. Meanwhile the related organization form and behavior learning changes in F2 generations will be clarified. The results above will offer the reliable evidence for ART intergenerational security on nervous system.