IL-22/IL-22受体信号通路在卵巢早衰发生发展中的作用及机制

项目名称： IL-22/IL-22受体信号通路在卵巢早衰发生发展中的作用及机制

项目编号： No.81471509

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 秦莹莹

作者单位： 山东大学

项目金额： 73万元

中文摘要： 以卵巢早衰（Premature Ovarian Failure, POF）为代表的生育力降低是妇科内分泌领域的常见病、棘手病，是导致女性不孕不育的重要原因之一。既无可靠的标记物预测其发生，也无有效的治疗措施，POF的病因研究及识别高风险人群十分必要。本课题组前期研究首次发现IL-22在POF患者中显著升高，卵巢和颗粒细胞均表达IL-22受体，推测IL-22/IL-22Rs信号通路异常可能参与POF的发生。目前尚无IL-22与卵巢功能的相关报道。本课题组拟在前期研究的基础上，借助体外实验和动物模型，从卵巢激素合成、细胞增殖凋亡、其他炎性因子协同、JAK-STAT/MAPK/PI3K-AKT信号通路等方面，深入探讨IL-22/IL-22受体信号通路异常影响卵巢功能的分子机制，明确免疫性卵巢炎在POF发生发展中的作用，为POF临床诊断、分型、干预和病情跟踪提供依据。

中文关键词： 卵巢早衰；自身免疫；白介素22；白介素22受体；发生机制

英文摘要： Premature ovarian failure (POF), the representative and final stage of diminished ovarian reserve, is one of the commonest diseases responsible for female infertility. Neither reliable biomarkers to predict its occurrence or effective treatment have been discovered. Since the etiology of majority of POF patients remain unknown, how to identify high- risk population beforehand become necessary. It is presumed that POF might be the result of interaction of endogenous genetic defects and exogenous stimulating factors. Previous studies suggest that autoimmune imbalance may be involved in POF. However, the mechanism is elusive. Our preliminary data revealed that the level of serum IL-22 was significantly higher in the idiopathic POF group compared with controls, and IL-22 receptor complex (IL-22R1 / IL-10R2) were expressed in human ovary and granulosa cells. It has been reported that the binding of IL-22 with its receptor complex could activate the downstream signaling pathways of JAK-STAT and MAPK. Therefore, our results suggest that IL-22/IL-22Rs signaling pathway may participate in the development of POF. There is no related report at present. Based on previous results, we will explore the molecular mechanism of IL-22/IL-22 receptor signaling pathway on ovarian function by studies both in vitro and in vivo. The results will provide new clues to clarify the contribution of autoimmune oophoritis for the etiology of POF. The project would be helpful for clinical diagnosis, prevention, interference, and treatment, especially for women with diminished ovarian reserve.

英文关键词： POF;autoimmunity;IL-22;IL-22 receptors;mechanism