卵裂中胚胎碎片形成是人类体外受精常见现象，但其形成机制尚不清楚。申请者通过临床观察及建立的模拟小鼠精子激活力减弱技术，发现卵激活强度（AIO）不足与胚胎卵裂碎片形成相关。本项目将在此基础上进一步阐明AIO与胚胎碎片形成的关系及临床对策。拟采用激活力减弱小鼠精子进行显微授精，联合辅助激活法，构建不同AIO胚胎模型，观测碎片化的亚微结构改变与钙信号的联系，比较基因表达谱及骨架蛋白动力学调控相关基因的表达，以分析AIO异常导致胚胎碎片形成的分子机制。且建立出生小鼠模型，进一步探究AIO对胚胎后期发育影响。同时通过人精子激活力检测的新技术，在临床上验证AIO与胚胎碎片的关系，通过检测人类捐赠废胚的相关分子，在人类胚胎验证上述发现的碎片形成机制，并综合临床显微授精辅助激活的资料分析辅助激活的利弊。本项目将不仅阐明AIO相关的胚胎碎片形成机制，而且为人胚质量分析提供新理论，对辅助激活应用提供新策略。

Fragmentation during embryonic cleavage is quite common in human in-vitro fertilization embryos, but the underlying mechanism is unclear. Our previous clinical observation and the model research through new established technique to artificially decrease mice sperm activation ability, suggest that activation intensity of oocyte (AIO) correlates with embryo fragmentation. On this basis, this project will further clarify the corelation between AIO and fragmentation and provide clinical strategy. To construct divers AIO embryo models, sperms with different artificially decreased activation ability will be used in intracytoplasmic sperm injection, and combine with different intensity of assisted oocyte activation. Comparing these models, we will first analyze the correlation between Ca2+ message and submicron change of fragmentation. At the same time, the gene expression pattern and cytoskeleton correlated gene expression of AIO models will be detected to determine the molecular mechanism of embryo fragmentation caused by abnormal AIO. Further,we will construct adult mice models to detect the effects of AIO on embryonic late development. Also, we will use the new technique that we have set up to examine the activation ability of human sperms, so to validate the correlation of AIO and embryo fragmentation in clinic. Then we will detect expression patterns of the associated genes as above in the denoted human embryos, so to validate the mechanism of fragmentation found in mouse embryonic model in human embryo. We will also evaluate the assisted oocyte activation techniques following intracytoplasmic sperm injection based on clinical samples. Our research will not only describe the AIO correlated mechanism of embryo fragmentation, but also provide novel theory for evaluation of human embryo quality and strategies for application of assisted oocyte activation technique following intracytoplasmic sperm injection.