我们前期研究结果证实NPPC与其受体NPR2维持了卵母细胞的成熟阻滞。进一步研究表明，FSH通过上调，而LH 可升高卵丘细胞中钙离子水平，直接下降鸟苷酸环化酶NPR2 的活性来诱导卵母细胞成熟。但是FSH上调，LH 引起钙离子升高、NPR2失活的分子机理不清楚。本项目将利用卵母细胞体外成熟培养模型，筛选E2上调NPPC/NPR2、LH诱导表皮样生长因子表达、EGF 受体引起卵丘细胞中钙离子升高以及钙离子升高导致NPR2 构象改变或与NPPC 结合率下降的作用机制。卵母细胞成熟排卵引起精子趋化的机制。并利用基因敲除小鼠模型进行功能验证。通过上述研究，最终确定促性腺激素通过调节NPPC/NPR2的表达来精确控制卵母细胞成熟的分子机理；排卵引起精子趋化受精的起始信号。为建立完善卵母细胞体外成熟体系、提高卵母细胞体外成熟质量提供理论基础，同时又对人类相关的临床研究和应用具有一定的借鉴意义。

Our previous results indicate that natriuretic peptide precursor C (NPPC, also commonly known as C-type natriuretic peptide, CNP) produced by follicular mural granulosa cells stimulates the generation of cyclic guanosine 3’,5’-monophosphate (cGMP) by its cognate natriuretic peptide receptor NPR2 in cumulus cells, maintain meiotic arrest of oocyte within antral follicle. Further studies suggest that FSH via E2 upregulates,but LH downregulates the expression of NPPC/NPR2. LH induces the expression of epidermal growth factor (EGF)-like proteins in mural granulosa cells that act on cumulus cells to trigger oocyte maturation.The activation of EGF receptor could decrease NPR2 activity by elevating calcium in cumulus cells, which is essential to induced oocyte maturation. However, it is not clear how LH increases calcium in cumulus cells, and how LH decreases NPR2 activity by elevating calcium. The signal for the chemotactic responsiveness in mammals is also unclear. The objective of the present project is to study the mechanism LH on calcium levels, NPR2 conformation,the rate of NPPC binding to NPR2, and to analysis their roles in LH-induced low cGMP levels and oocyte maturation; the role of NPPC on sperm chemotaxis and fertilization. These results will further understand the mechanism of LH-induced oocyte maturation, setup new culture system to improve oocyte quality for animal reproduction, and provide foundation for clinic application.