Zhang Bochun, Qi Xinyu, Zhao Yue, Li Rong, Zhang Chunmei, Chang Hsun-Ming, Pang Yanli, Qiao Jie
1 Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing, China.
2 Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China.
Reprod Sci. 2018 Dec;25(12):1629-1636. doi: 10.1177/1933719118756772. Epub 2018 Feb 13.
Hyperhomocysteinemia, chronic low-grade inflammation, and insulin resistance are predominant features in women with polycystic ovary syndrome (PCOS). CD14CD16 inflammatory monocytes are elevated in cardiovascular diseases and diabetes, in which inflammation is one of the pathogenesis. We aimed to determine whether homocysteine levels are associated with monocyte subtypes or insulin resistance in women with PCOS.
A cross-sectional study was conducted between December 2014 and June 2015 at Peking University Third Hospital. Among 196 Chinese patients with PCOS enrolled, 102 had homocysteine levels ≥10 µmol/L and 94 exhibited normal homocysteine levels. Monocyte surface markers and related cytokines were detected in peripheral blood samples using a flow cytometry, and data on insulin resistance and homocysteine levels were collected.
Our results showed that fasting insulin and homeostasis model assessment indices that reflect the severity of insulin resistance were increased in the hyperhomocysteinemia PCOS group. Simple linear regression analysis revealed that homocysteine level is one of the influence factors of insulin resistance in PCOS. Compared with the normal homocysteine group, patients with hyperhomocysteinemia had increased numbers of CD14CD16 inflammatory monocyte in their peripheral blood and elevated plasma levels of interleukin-1β and interleukin-6, 2 typical cytokines secreted by the inflammatory monocytes. Unlike CD14CD16 nonclassical monocytes, CD14CD16 inflammatory monocytes are characterized by high expression of Human leukocyte antigen-antigen D related (HLA-DR).
Our findings indicate that CD14CD16 inflammatory monocytes are associated with hyperhomocysteinemia and insulin resistance in patients with PCOS. Notably, CD14CD16 monocytes may contribute to the pathogenesis of insulin resistance in women with PCOS.
高同型半胱氨酸血症、慢性低度炎症和胰岛素抵抗是多囊卵巢综合征（PCOS）女性的主要特征。CD14CD16炎性单核细胞在心血管疾病和糖尿病中升高，炎症是其发病机制之一。我们旨在确定PCOS女性的同型半胱氨酸水平是否与单核细胞亚群或胰岛素抵抗相关。
2014年12月至2015年6月在北京大学第三医院进行了一项横断面研究。在196名纳入研究的中国PCOS患者中，102名同型半胱氨酸水平≥10µmol/L，94名同型半胱氨酸水平正常。使用流式细胞术检测外周血样本中的单核细胞表面标志物和相关细胞因子，并收集胰岛素抵抗和同型半胱氨酸水平的数据。
我们的结果显示，高同型半胱氨酸血症PCOS组中反映胰岛素抵抗严重程度的空腹胰岛素和稳态模型评估指标升高。简单线性回归分析显示，同型半胱氨酸水平是PCOS中胰岛素抵抗的影响因素之一。与同型半胱氨酸正常组相比，高同型半胱氨酸血症患者外周血中CD14CD16炎性单核细胞数量增加，血浆中白细胞介素-1β和白细胞介素-6水平升高，这是炎性单核细胞分泌的2种典型细胞因子。与CD14CD16非经典单核细胞不同，CD14CD16炎性单核细胞的特征是人类白细胞抗原-D相关（HLA-DR）高表达。
我们的研究结果表明，CD14CD16炎性单核细胞与PCOS患者的高同型半胱氨酸血症和胰岛素抵抗相关。值得注意的是，CD14CD16单核细胞可能在PCOS女性胰岛素抵抗的发病机制中起作用。
