Li Shengxian, Qi Jia, Tao Yongzhen, Zhu Qinling, Huang Rong, Liao Yu, Yue Jiang, Liu Wei, Zhao Hanting, Yin Huiyong, Sun Yun
Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Reproduction. 2020 Feb;159(2):159-169. doi: 10.1530/REP-19-0136.
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women usually accompanied by lipid metabolic disorders. However, it remains unknown whether arachidonic acid (AA) and its metabolites in follicular fluid (FF) were altered in PCOS patients. This study was intended to measure the levels of AA and its metabolites in the FF of non-obese PCOS patients that underwent in vitro fertilization (IVF) and to explore the possible causes of the alterations. Thirty-nine non-obese women with PCOS and 30 non-obese women without PCOS were enrolled. AA and its metabolites were measured by liquid chromatography-mass spectrometry. The levels of AA metabolites generated via cyclooxygenase-2 (COX-2) pathway and cytochrome P450 epoxygenase pathway but not lipoxygenase (LOX) pathway were significantly higher in the FF of PCOS patients. The metabolites generated via COX-2 pathway were significantly correlated with levels of testosterone and fasting insulin in serum. The in vitro study further demonstrated that insulin but not testosterone could promote the IL-1β and hCG-induced COX-2 expression and prostaglandin E2 (PGE2) secretion in primary human granulosa cells. In conclusion, there was an elevation in AA metabolites in FF of PCOS patients. Insulin played a pivotal role in the increased AA metabolites generated via COX-2, which could be interpreted as another novel molecular pathophysiological mechanism of PCOS.
多囊卵巢综合征（PCOS）是育龄女性中最常见的内分泌紊乱疾病，通常伴有脂质代谢紊乱。然而，PCOS患者卵泡液（FF）中的花生四烯酸（AA）及其代谢产物是否发生改变仍不清楚。本研究旨在测量接受体外受精（IVF）的非肥胖PCOS患者FF中AA及其代谢产物的水平，并探讨其改变的可能原因。招募了39名非肥胖PCOS女性和30名非肥胖非PCOS女性。通过液相色谱 - 质谱法测量AA及其代谢产物。PCOS患者FF中通过环氧合酶 - 2（COX - 2）途径和细胞色素P450环氧化酶途径而非脂氧合酶（LOX）途径产生的AA代谢产物水平显著更高。通过COX - 2途径产生的代谢产物与血清中睾酮和空腹胰岛素水平显著相关。体外研究进一步表明，胰岛素而非睾酮可促进原代人颗粒细胞中IL - 1β和hCG诱导的COX - 2表达及前列腺素E2（PGE2）分泌。总之，PCOS患者FF中AA代谢产物升高。胰岛素在通过COX - 2产生的AA代谢产物增加中起关键作用，这可被解释为PCOS的另一种新的分子病理生理机制。
