多囊卵巢综合征合并代谢综合征患者卵巢颗粒细胞瘦素启动子甲基化的研究  

Methylation of leptin promoter in ovarian granulosa cells of polycystic ovary syndrome-metabolic syndrome patients

作　　者：袁浩 牛志宏[2] YUAN Hao;NIU Zhi-hong(Department of Obstetrics and Gynecology,Tonglu First People′s Hospital,Tonglu 311500,China;Center for Reproductive Medicine,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China)

机构地区：[1]浙江省桐庐县第一人民医院妇产科,桐庐311500 [2]上海交通大学医学院附属瑞金医院生殖医学中心,上海200025

出　　处：《上海交通大学学报（医学版）》2018年第11期1312-1317,共6页Journal of Shanghai Jiao tong University:Medical Science

基　　金：上海市自然科学基金(16ZR1421500)~~

摘　　要：目的·研究多囊卵巢综合征(polycystic ovary syndrome,PCOS)合并代谢综合征(metabolic syndrome,MS)患者卵巢颗粒细胞瘦素基因(leptin,Lep)启动子甲基化及瘦素分泌特征。方法·选取2016年9—12月于上海交通大学医学院附属瑞金医院生殖医学中心因输卵管因素进行体外受精助孕的患者20例,单纯PCOS患者(PCOS组)及PCOS合并MS患者(PCOS-MS组)各10例。化学发光法检测血清性激素和糖代谢指标,甘油磷酸氧化酶-过氧化物酶-4-氨基安替比林和酚法检测脂代谢指标,酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)检测血清及卵泡液瘦素水平,联合亚硫酸氢钠的限制性内切酶分析法检测颗粒细胞瘦素基因启动子甲基化程度,并采用Wilcoxon秩和检验和χ~2检验对结果进行统计分析。结果·2组患者年龄及基础性激素水平并无差异。与PCOS组相比,PCOS-MS组胰岛素抵抗指数、三酰甘油水平显著升高(P=0.045,P=0.044),高密度脂蛋白水平有所下降(P=0.048),血清及卵泡液中瘦素水平明显升高(P=0.031,P=0.042),黄素化颗粒细胞瘦素DNA启动子转录起始位点上游299～556序列CpG岛甲基化位点明显减少(P=0.026),优质胚胎率也有所下降(P=0.043)。结论·血清及卵泡液中瘦素水平的升高,黄素化颗粒细胞瘦素DNA启动子甲基化程度的降低及优质胚胎比例的下降,可能是导致PCOS合并MS患者生育力下降的部分原因。Objective · To investigate the characteristics of leptin secretion and DNA methylation of leptin gene of ovarian granulosa cells in patients with polycystic ovary syndrome （PCOS） associated with metabolic syndrome （MS）. Methods · Twenty patients underwent in vitro fertilization for fallopian tube factor at the Reproductive Medical Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from September to December 2016 were selected. They were divided into two groups, i.e. PCOS group （n=10） and PCOS-MS group （n=10）. Chemiluminescence method was used to detect serum sex hormones and glucose metabolism indexes. Glycerol phosphate oxidase-peroxidase-4-aminoantipyrine and phenolic method was used to detect lipid metabolism indexes. Enzyme-linked immunosorbent assay （ELISA） was used to detect the concentration of leptin in serum and follicular fuid. Combined bisulfte restriction analysis was used to test methylation level of the leptin DNA promoter in ovarian granulosa cells. Wilcoxon rank and χ2 test were used for statistical analysis. Results · There was no difference in age and basic hormone levels between two groups. Compared with the PCOS group, the insulin resistance index and triglyceride level in patients with PCOS-MS group were signifcantly higher （P=0.045, P=0.044）, high density lipoprotein level was decreased signifcantly （P=0.048）, the level of leptin in serum and follicular fuid was increased signifcantly （P=0.031, P=0.042）, the methylation sites of CpG island in leptin DNA promoter upstream 299-556 sequence of luteinized granulosa cells were reduced signifcantly （P=0.026）, and the good quality embryo rate was signifcantly lower （P=0.043）. Conclusion · The leptin levels in the serum and follicular fuid of patients with PCOS-MS are elevated, accompanied by a decrease in the methylation level of the leptin DNA promoter in luteinized granulosa cells and in the proportion of high-quality embryos, which may be one of the reasons leading to the de

关 键 词：多囊卵巢综合征 代谢综合征 瘦素 甲基化 胚胎 

分 类 号：R715.9[医药卫生—妇产科学]