Enhanced Inflammatory Transcriptome in the Granulosa Cells of Women With Polycystic Ovarian Syndrome
Enhanced Inflammatory Transcriptome in the Granulosa Cells of Women With Polycystic Ovarian Syndrome
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DOI：
10.1210/jc.2015-4275
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发表时间：
2016-09-01
影响因子：
5.8
通讯作者：
Richards, JoAnne
中科院分区：
文献类型：
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作者：
Adams, Jaye;Liu, Zhilin;Richards, JoAnne
内容：多囊卵巢综合征（PCOS）是育龄期妇女最常见的内分泌疾病，与全身性低度炎症反应有关。目的：我们提出PCOS患者排卵期卵泡内炎症反应的增加或改变。设计：在从PCOS和非PCOS患者收集的颗粒黄体细胞（GC）中进行基因谱分析和定量PCR（qPCR）分析。PCOS妇女接受体外受精与血清和卵泡液（FF）水平的细胞因子和趋化因子进行比较。设置：这是一个大学为基础的研究。患者：21名PCOS和45名对照患者被招募：从患者数据文件中提取人口统计学、激素、体重指数和妊娠结局。干预措施：在与人绒毛膜促性腺激素，DHT，IL-6，或IL-8;主要结果测量：比较培养前后血清/FF细胞因子水平和GC细胞因子表达与体重指数的关系。1）PCOS GC表达升高的编码细胞因子、趋化因子和免疫细胞标志物的转录物，2）基于基因谱和qPCR分析，肥胖PCOS患者定义了一种独特的PCOS疾病亚型，其具有促炎和免疫相关因子的最显著增加，和3）人绒毛膜促性腺激素和DHT增加培养的GC中的细胞因子产生，而细胞因子增强细胞因子和血管基因，表明高雄激素血症/LH升高和肥胖在PCOS妇女增加卵泡内细胞因子production.Conclusions：卵泡内雄激素和细胞因子可能包括一个局部调节回路，影响GC表达的细胞因子和趋化因子和免疫细胞的存在;该环在肥胖型PCOS亚型中进一步增强。
Context: Polycystic ovarian syndrome (PCOS), the most common endocrine disorder of reproductive-aged women, is associated with systemic low-grade inflammation.Objective: We propose that increased or altered intrafollicular inflammatory reactions also occur in periovulatory follicles of PCOS patients.Design: Gene profiling and quantitative PCR (qPCR) analyses in granulosa-lutein cells (GCs) collected from PCOS and non-PCOS women undergoing in vitro fertilization were compared with serum and follicular fluid (FF) levels of cytokines and chemokines.Setting: This was a university-based study.Patients: Twenty-one PCOS and 45 control patients were recruited: demographic, hormone, body mass index, and pregnancy outcomes were abstracted from patient data files.Interventions: GC cytokine/chemokinem RNAs were identified and analyzed by gene-chip microarrays/qPCR before and after culture with human chorionic gonadotropin, DHT, IL-6, or IL-8; serum/FF cytokine levels were also analyzed.Main Outcome Measures: Relative serum/FF cytokine levels and GC cytokine expression before and after culture were compared and related to body mass index.Results: The following results were found: 1) PCOS GCs express elevated transcripts encoding cytokines, chemokines, and immune cell markers, 2) based on gene profiling and qPCR analyses, obese PCOS patients define a distinct PCOS disease subtype with the most dramatic increases in proinflammatory and immune-related factors, and 3) human chorionic gonadotropin and DHT increased cytokine production in cultured GCs, whereas cytokines augmented cytokine and vascular genes, indicating that hyperandrogenism/elevated LH and obesity in PCOS women augment intrafollicular cytokine production.Conclusions: Intrafollicular androgens and cytokines likely comprise a local regulatory loop that impacts GC expression of cytokines and chemokines and the presence of immune cells; this loop is further enhanced in the obese PCOS subtype.