多囊卵巢综合征（PCOS）是排卵障碍性不孕的最常见病因，发病机制不明。长链非编码RNA（lncRNA）在人类疾病、发育、干细胞等领域发挥重要调控作用，但在生殖领域的作用鲜有报道，其在卵巢功能调控及PCOS发病中的作用亦不明确。申请人前期通过lncRNA微阵列基因芯片检测发现：在PCOS患者卵泡液颗粒细胞中有862条lncRNA的表达水平出现显著变化；初步筛选4条lncRNA进行检测，发现其表达趋势与芯片结果相符，且表达水平与患者的取卵数呈正相关关系，提示lncRNA表达失调可能影响颗粒细胞功能进而影响卵泡发育。我们另一研究发现，lncRNA NEAT1在高龄不孕女性中的表达水平显著下调，而此前有动物研究表明，NEAT1缺失引起黄体功能缺陷而导致不孕，提示lncRNA可能参与调控卵巢性激素合成与代谢功能。本项目拟通过体内外模型，探索差异lncRNA在PCOS中的调控作用和机制。

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of reproductive age, whose etiology is still unknown. It is reported that long non-coding RNAs (lncRNAs) play important roles in human diseases, development and stem cells, however, its roles remains unclear in reproductive medicine, including the regulatory function involved in ovary and the mechanism of polycystic ovary syndrome. Our previous study showed that a total of 862 lncRNA transcripts were dysregulated in mural granulose cells from women with PCOS, compared with those from women with normal ovarian reserve. The expressions of the 4 chosen lncRNAs were found to be consistent with the result of microarray, and they both have a positive correlation with the number of retrieved oocytes, suggesting that the dysregulation of lncRNAs may affect the physiological function of granulosa cells and follicular development. In addition, we found that the expression level of lncRNA NEAT1 was significantly decreased in women with advanced maternal age. Previous animal studies showed that NEAT1 deletion might cause luteal phase deficiency and lead to infertility, suggesting that lncRNA may be involved in the steroid metabolism. We aim to explore the regulatory effect of lncRNA on the mechanism of polycystic ovary syndrome by using granulosa cell model and animal model, and it would provide prevention or treatment targets for female infertility associated with PCOS and improve their outcomes in assisted reproductive technology (ART).