早发性卵巢功能不全中AQP7对卵泡发育的作用及机制研究

Premature ovarian insufficiency (POI) is a reproductive endocrinological disease characterized by ovulation dysfunction with various symptoms and causes. Our preliminary study showed that expression of aquaporin-7 (AQP7), the water channel was down-regulated in oocytes and granular cells of POI women and we found a significantly negative correlation between AQP7 expression and serum baseline follicle-stimulating hormone (FSH). In vitro oocyte maturation model indicated that AQP7 expression and location in oocytes showed dynamic changes from the GV stage to the MⅡ stage. In vitro granular cells culture showed that FSH down-regulated AQP7 expression via FSH receptor.The findings suggest that AQP7 may play an important role in follicle development, and, AQP7 expression downregulation and dysfunction are probably potential causes of POI. The study starts from analyzing the characteristics of AQP7 expression and location in oocytes and granular cells of POI patients. Oocytes and granular cells conditional gene knock-out mice and in vitro operation models are utilized to clarify effects of AQP7 knock-out on oocyte development and permeability of granular cells. We try to clarify the mechanisms underlying the regulation effect of high concentration FSH on AQP7 via FSHR-cAMP-PKA-CREB/AP-1 pathway in POI. The results will provide a new insight into the mechanisms of follicle development, and, be helpful for the improvement of reproductive ability for POI patients in clinical practice in future.

早发性卵巢功能不全（POI）为临床高度异质、病因混合复杂的一类排卵障碍疾病。我们前期研究发现POI女性卵母细胞和颗粒细胞水通道蛋白AQP7表达量显著下降，且与血清基础FSH水平显著负相关；体外卵母成熟模型显示 AQP7在GV期和MⅡ期呈现动态差异表达与分布；体外颗粒细胞培养显示高浓度FSH通过其受体FSHR下调AQP7表达，提示AQP7在卵泡发育中发挥重要功能，而AQP7表达和功能异常为POI的潜在病因。本项目拟从分析POI患者AQP7表达分布特征入手，应用卵母细胞、颗粒细胞条件性基因敲除小鼠和体外培养模型，研究AQP7敲除对小鼠卵母细胞发育和颗粒细胞通透性的影响；力图阐明POI中高FSH通过FSHR-cAMP-PKA-CREB/AP-1途径对颗粒细胞AQP7实施调控作用的分子机制。其成果将为卵泡发育提供新的理论基础，对医学临床实践中改善POI患者的生殖能力有着一定的指导意义。

早发性卵巢功能不全（POI）为临床高度异质、病因混合复杂的一类排卵障碍疾病。我们前期研究发现POI女性卵母细胞和颗粒细胞水通道蛋白AQP7表达量显著下降，且与血清基础FSH水平显著负相关；体外卵母成熟模型显示 AQP7在GV期和MⅡ期呈现动态差异表达与分布；体外颗粒细胞培养显示高浓度FSH通过其受体FSHR下调AQP7表达，提示AQP7在卵泡发育中发挥重要功能，而AQP7表达和功能异常为POI的潜在病因。本项目从分析POI患者AQP7表达分布特征入手，应用卵母细胞、颗粒细胞体外培养模型，研究AQP7对小鼠卵母细胞发育和颗粒细胞通透性的影响；阐明了POI中高FSH通过FSHR-cAMP-PKA-CREB/AP-1途径对颗粒细胞AQP7实施调控作用的分子机制。结合上述结果，本研究为卵泡发育提供新的理论基础，对医学临床实践中改善POI患者的生殖能力有着一定的指导意义。项目资助发表SCI论文2篇，核心期刊论文1篇，待发表论文2篇。项目执行期间培养在读博士研究生1名，培养在读硕士研究生2名。项目预算经费20万元，支出12.0815万元，各项支出与预算相符，结余经费7.9185万元，结余资金占比39.59%。结余经费计划用于本项目后续支出。.