Kisspeptin-54通过调控人颗粒细胞血管活性因子表达参与卵巢过度刺激综合征发生的分子机制研究

卵巢过度刺激综合征(OHSS)是辅助生殖技术最严重的并发症，起因于血管活性因子(VEGF/ANGPT1/SPRY2)高表达，尚无有效的早期预防和治疗方法。Kisspeptin-54可替代传统hCG扳机促进卵母细胞成熟，同时降低不孕症患者重度OHSS发生率。我们前期研究发现OHSS患者卵泡液Kisspeptin-54低表达，在人颗粒细胞中加入Kisspeptin-54可抑制VEGF/ANGPT1/SPRY2表达，推测Kisspeptin-54可能通过降低VEGF/ANGPT1/SPRY2表达阻断OHSS发生，但具体调控机制不明。本课题将采用细胞模型从受体、信号通路和转录因子水平研究Kisspeptin-54抑制血管活性因子合成的分子机制，筛选OHSS发生的分子靶标；采用OHSS大鼠模型研究Kisspeptin-54是否可阻断OHSS发生及机制，为OHSS早期预防和靶向治疗提供新思路和方法。

Ovarian hyperstimulation syndrome (OHSS) is a serious complication during in vitro fertilization (IVF) procedure. The overexpressed VEGF, ANGPT1, and/or SPRY2 are suggested to be major factors that contribute to the pathogenesis of OHSS. To date, there is no efficient method for the early prevention and treatment of OHSS. Mimic the hCG effect, Kisspeptin-54 has been used to trigger oocyte maturation and can reduce the development of severe OHSS. Our preliminary results showed that OHSS patients had significantly lower Kisspeptin-54 levels in the follicle fluid. In addition, treatment of granulosa cells with Kisspeptin-54 downregulated VEGF, ANGPT1 and SPRY2 expression. These results suggest that Kisspeptin-54 suppresses OHSS development by inhibiting VEGF/ANGPT1/SPRY2 expression in human granulosa cells. However, the underlying molecular mechanism remains unknown. In this research proposal, we aim to examine the effects of Kisspeptin-54 on VEGF/ANGPT1/SPRY2 expression in human granulosa cells and explore the underlying molecular mechanism in order to identify the therapeutic target for OHSS. Using OHSS rat model, Kisspeptin-54 injection will be performed to study the effect of Kisspeptin-54 on the pathogenesis of OHSS and related mechanisms. These results will provide not only important insights into the molecular mechanisms mediating Kisspeptin-54-regulated OHSS but also identify potential targets that can be used for the prevention and treatment of OHSS.