热应激对动物生殖影响日益突显，已成国际研究热点。申请者前期研究发现，热应激能级联激活小鼠囊胚ERK1/2信号通路，但在附植前哪个时期激活、是否调控胚胎耐热应激损伤及其机制尚不清楚。本研究拟以ERK1/2信号通路参与调控小鼠胚胎耐热损伤及其受内、外因调节为理论假说，从附植前胚胎不同发育时期入手，以胚胎耐热损伤及其受ERK1/2信号级联调控为研究切入点，利用发育生物学、分子生物学和细胞生物学等方法，研究热应激时小鼠附植前胚胎：①各发育时期获得耐热能力；②ERK1/2信号通路级联（Ras-ERK）激活；③ERK1/2信号通路调控耐热损伤（氧化和凋亡）和调节因子（HSPs）合成；④母源性胚胎因子（CSF2和IGF-1）和黄芩苷（解热安胎）对胚胎耐热的影响及ERK1/2信号通路调控。明确ERK1/2信号激活时期及其对胚胎耐热的级联调控机制，为揭示热应激影响动物生殖机理和预防夏季奶牛不孕提供理论依据。

Heat stress disturbing animal reproduction which has been increasingly more and more prominent is, in nowadays, becoming a hotspot in the international research. Our previous research revealed that heat stress activated ERK1/2 signal cascade transduction in mouse blastocyst. However, neither at which stage of the preimplantation embryonic development activated or whether it regulates thermotolerance of the embryo to heat stress nor the signal transduction mechanism involved in the process is clear. We hypothesize that ERK1/2 signal pathway participates in regulating or control of embryonic thermotolerance, which is influenced by both internal and external factors. In vitro derived mouse embryos in their various preimplantation development stages (2-4 cells to blastocyst) will be heat-stressed and advanced technologies in modern developmental biology, molecular biology and cytobiology will be employed to study：①developmental acquisition ability of the embryo in thermotolerance to heat stress; ②cascade activation (Ras-ERK) of ERK1/2 signal pathway; ③regulating and control of ERK1/2 signal pathway in thermotolerance of the embryo to heat-stress including antioxidation and antiapoptosis or regulating embryo itself to produce cytoprotective factors; and ④influence of maternal embryokines including colony-stimulating factor 2（CSF2）and insulin-like growth factors-1 (IGF-1) and baicalin (antipyretic and tocolysis) on the embryonic thermotolerance and their regulations to ERK1/2 signal pathway of the embryo under heat stress. The results will reveal activation stage of ERK1/2 signal pathway and its cascade regulating mechanism in thermotolerance of preimplantation mouse embryo under heat stress, which will provide a theoretic base for revealing the mechanism of heat stress disrupting animal reproduction and preventing summer infertility of dairy cows.