脯氨酰寡肽酶（POP）在卵泡发育中的作用及其异常表达与PCOS排卵障碍关系的研究

脯氨酰寡肽酶（POP）是特异水解脯氨酸残基羧基端肽键的丝氨酸蛋白酶，研究报道POP高表达于小鼠卵巢，发情期间POP活性显著增加，但其在卵巢中的功能尚不清楚。我们发现POP高表达于小鼠有腔卵泡壁层颗粒细胞和卵丘细胞，POP抑制剂减少了颗粒细胞孕酮分泌和抑制了LH诱导的卵丘扩散，提示POP可能通过影响颗粒细胞黄素化和卵丘扩散参与排卵过程；多囊卵巢综合症（PCOS）是女性生殖内分泌和代谢功能异常导致的排卵障碍性疾病，我们发现PCOS模型小鼠卵巢POP表达明显减少，提示POP表达异常可能与PCOS相关。本课题拟在动物和细胞水平，通过过表达和抑制POP，探索POP对颗粒细胞黄素化和卵丘扩散的影响及其机制；通过构建PCOS小鼠模型和分离PCOS病人颗粒细胞，探索POP异常表达与PCOS排卵障碍的关系。该研究将有助于了解POP在卵泡发育和排卵中的作用，为排卵异常相关疾病诊断治疗提供理论基础和实验依据。

Prolyl oligopeptidase (POP) is a serine protease that cleaves peptides at carboxyl side of an internal proline. Studies showed that POP was highly expressed in mouse ovaries. During estrus, POP activity was significantly increased, however, the function of POP in ovaries is still unclear. In previous studies, we found that POP was highly expressed in mural granulosa cells and cumulus cells in antral follicles. POP inhibitor decreased the progesterone production of granulosa cells and inhibited the LH induced cumulus expansion, which suggests that POP is possibly involved in ovulation through regulating granulosa cell luteinization and cumulus expansion. Polycystic ovary syndrome (PCOS) is the most prevalent ovulatory disorder due to female reproductive endocrine and metabolic dysfunction. We found that POP was decreased in mouse model of PCOS, implying that the abnormal expression of POP is possibly related to PCOS. In this study, we will explore the function and mechanism of POP on granulosa cell luteinization and cumulus expansion through overexpression of POP and inhibition of POP at animal level and cell level. We will construct mouse model of PCOS, culture granulosa cells from PCOS patients and further explore the relationship between deregulated expression of POP and ovulatory disorder of PCOS. Completion of this study will be instrumental to understand the function of POP on follicular development and provide the theoretical foundation and experiment evidences for diagnosis and treatment of ovulatory disorder related diseases.