NGF在多囊卵巢综合征发生中的作用及其机制

Polycystic ovarian syndrome (PCOS) is the most common cause of female infertility. This complex disorder is characterized by hyperandrogenism, chronic anovulation, and polycystic ovaries. However, the specific pathogenesis of PCOS is still unknown. It has been reported that excessive ovarian NGF production causes a polycystic ovary-like syndrome in mice models. Moreover, an overproduction of NGF has been shown in PCOS patients. According to our study, NGF promotes the proliferation of granulosa cells (GCs) through regulating p21, and TrkA (the receptor of NGF) regulates cumulus expansion and ovulation mediated by IL-6 (interleukin-6) in mice. Abnormal ovulation and GCS’ proliferation is the important pathologic features of PCOS, but so far the role of NGF in the PCOS occurrence is not clear. Based on the above, we propose to examine the expression of NGF in serum, follicular fluid and GCs from PCOS patients; determine which signal pathway play a role in PCOS; and validate all the above in the rat model of PCOS. Our goal is to gain insight into how NGF modulates granulosa cell function in PCOS patients, in hope to better understand the pathology of PCOS and develop new diagnostic and treatment methods.

多囊卵巢综合征（PCOS）是导致女性不孕最常见的因素，主要表现为高雄激素血症，慢性无排卵和卵巢多囊化。但其发病的具体分子机制至今不明。有研究表明，小鼠卵巢内高浓度的NGF能够导致类似多囊卵巢综合征的症状，且PCOS患者血及卵泡液中NGF的含量显著升高。而且我们前期的研究表明，小鼠中NGF可通过调控p21影响颗粒细胞（GCs）增殖，其受体TrkA通过白细胞介素6（IL-6）调控卵丘扩展及排卵，而颗粒细胞增殖及排卵异常是PCOS的重要特征。这些证据提示NGF在PCOS中发挥作用，但NGF通过何种机制影响PCOS的发生尚不明确。本课题通过检测PCOS患者血、卵泡液及GCs中NGF表达含量，鉴定出介导NGF影响PCOS发生的信号通路，最后在PCOS患者及大鼠模型中进行验证。本研究有助于了解NGF在PCOS发病过程中的作用，深入探讨PCOS病理生理过程，为该病的预防与治疗提供新的潜在靶标。