LPCAT3在多囊卵巢综合征子宫内膜蜕膜化中的作用及机制

Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic diseases in women of childbearing age. However, the causes of endometrial dysfunctions in PCOS still remain unknown. Our previous studies demonstrated the elevation of LPCAT3 in endometrium in receptive phase, using RNA-seq and iTRAQ proteomics. There was also a close relationship between LPCAT3 and decidualization in PCOS patients. Diminished expression of LPCAT3 could induce cholesterol accumulation, promote cell proliferation and therefore inhibit decidualization of endometrial stromal cell significantly. Here, our first aim of this study is to demonstrate the involvement of LPCAT3 in endometrial decidualization. The second aim is to speculate the molecular mechanisms of LPCAT3 on decidualization. And thirdly, we aim to explore the possible role of LPCAT3 as a molecular marker or treatment target in decidualization. The exploration of these scientific problems will clarify the pivotal role of LPCAT3 in endometrial dysfunction in PCOS patients, and further improve the IVF outcomes.

多囊卵巢综合征（PCOS）是育龄期妇女最常见的生殖内分泌疾病，子宫内膜功能异常是其妊娠结局差的关键因素之一，但是其中的机理尚不明确。课题组利用RNA-seq和iTRAQ蛋白组学筛选到着床期人子宫内膜高表达的关键基因——LPCAT3，申请人前期预实验发现LPCAT3与PCOS患者子宫内膜蜕膜化障碍密切相关，同时发现敲减LPCAT3后细胞内胆固醇含量增加，促进细胞增殖，明显抑制间质细胞蜕膜化。因此申请人提出：LPCAT3在PCOS子宫内膜蜕膜化中发挥重要作用。为此本项目拟对如下科学问题进行研究：（1）LPCAT3在PCOS子宫内膜蜕膜化障碍中的作用；（2）LPCAT3通过调控胆固醇合成影响蜕膜化的分子机制；（3）LPCAT3作为PCOS患者子宫内膜蜕膜化障碍的标志物及治疗靶点的可行性。对这些问题的回答，将明确LPCAT3在PCOS子宫内膜蜕膜化中的作用，为进一步提高PCOS妊娠结局提供新思路。

多囊卵巢综合征（PCOS）是育龄期妇女最常见的内分泌代谢疾病之一，PCOS患者子宫内膜容受性下降是其妊娠结局差、着床率低、流产率高的关键因素之一，PCOS患者子宫内膜存在蜕膜化障碍，但其病因机制尚不清楚。本研究从课题组前期针对月经周期子宫内膜组织的转录组测序，筛选到溶血磷脂酰胆碱酰基转移酶LPCAT3在子宫内膜容受性建立中可能发挥重要作用，进一步通过收集PCOS患者子宫内膜组织，明确LPCAT3在PCOS患者中表达显著降低。在一系列体内体外研究中，我们发现LPCAT3在子宫内膜间质细胞蜕膜化中发挥重要作用，且进一步阐明了LPCAT3调控蜕膜化的分子机制：LPCAT3是通过影响脂质组成，进而影响子宫内膜间质细胞衰老调控子宫内膜间质细胞蜕膜化。本项目为解析PCOS患者流产率高、种植率低的临床现象提供了新的理论依据，提出LPCAT3作为重要脂质代谢酶参与调控子宫内膜容受性的新理论；同时脂质作为重要的细胞组成成分，其构成变化易检测易识别，可以为子宫内膜容受性的快速诊断提供新方法。