植入前胚胎的正常发育是辅助生殖治疗成功的前提，研究表明仅40-70%胚胎具备持续发育潜能。随着高通量测序技术的完善，近年来从遗传变异角度只能解释不到20%的病患的致病机理。项目申请人前期工作发现BTG4变异会造成母源性mRNA降解障碍，导致完全卵裂失败的发生，同时申请人在卵裂停滞病例中筛查到另一个mRNA调控因子ZFP36L2的罕见变异。为了进一步从mRNA精准调控层面研究人类胚胎卵裂停滞的原因，在本项目中，我们将在阐述ZFP36L2的致病分子机制的同时，对同为mRNA降解调控因子的ZFP36L2和BTG4导致表型的差异予以探究，并通过构建Btg4定点突变小鼠模型来深入探讨补救性治疗母源性因子缺陷的有效性及安全性。以期最终为BTG4及ZFP36L2基因作为卵裂停滞诊断标记分子的临床应用提供有力的实验支持，并加深对mRNA降解与植入前胚胎发育的关联性认识。

Normal development of preimplantation embryo is the premise of the success of assisted reproductive therapy. Previous research indicates that only 40-70% of embryos have the potential of sustainable development. With the improvement of high-throughput sequencing technology, less than 20% of the patients' pathogenic mechanism has been explained from the perspective of genetic variation in recent years. We have revealed that BTG4 variation can lead to complete cleavage failure via maternal mRNA degradation disorder. Moreover, we screened a rare variation of ZFP36L2, another mRNA cleaner in patient with embryonic arrest. In order to further study the causes of human embryonic arrest from the perspective of mRNA precise regulation. In this project, we will explore the phenotypic differences caused by ZFP36L2 and BTG4, while elaborating the pathogenic molecular mechanism of ZFP36L2, and further explore the effectiveness and safety of remedial injection after maternal factor defect by using Btg4 site-specific mutant mouse model. Our work will provide strong experimental support for the clinical application of BTG4 and ZFP36L2 genes as the diagnostic markers, and deepen the understanding of the relationship between maternal mRNA degradation and preimplantation embryo development.