• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验

多囊卵巢综合征患者滤泡液中的花生四烯酸诱导人卵巢颗粒细胞瘤细胞系(KGN)氧化应激,并作为一种应对方式上调 GDF15 的表达。

Arachidonic Acid in Follicular Fluid of PCOS Induces Oxidative Stress in a Human Ovarian Granulosa Tumor Cell Line (KGN) and Upregulates GDF15 Expression as a Response.

机构信息

Reproductive Medical Center, Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, China.

Cardiovascular Medicine Department, The First Hospital of Jilin University, Changchun, China.

出版信息

Front Endocrinol (Lausanne). 2022 May 11;13:865748. doi: 10.3389/fendo.2022.865748. eCollection 2022.

DOI:10.3389/fendo.2022.865748
PMID:35634503
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9132262/
Abstract

Polycystic ovarian ovary syndrome (PCOS) is the main cause of ovulatory infertility and a common reproductive endocrine disease of women in reproductive age. In addition, nearly half of PCOS patients are associated with obesity, and their total free fatty acids tend to increase. Arachidonic acid (AA) is a polyunsaturated fatty acid. Oxidation products of AA reacting with various enzymes[cyclooxygenases (COX), lipoxygenases (LOX), cytochrome P450s (CYP)] can change cellular mitochondrial distribution and calcium ion concentration, and increase reactive oxygen species (ROS) production. In this study, we analyzed the follicular fluid fatty acids and found higher levels of C20:4n6 (AA) in PCOS patients than in normal control subjects. Also, to determine whether AA induces oxidative stress (OS) in the human ovarian granulosa tumor cell line (KGN) and affects its function, we treated KGN cells with or without reduced glutathione (GSH) and then stimulated them with AA. The results showed that AA significantly reduced the total antioxidant capacity (TAC) and activity of antioxidant enzymes and increased the malondialdehyde (MDA), ROS and superoxide anion(O)levels in KGN cells. In addition, AA was also found to impair the secretory and mitochondrial functions of KGN cells and induce their apoptosis. We further investigated the downstream genes affected by AA in KGN cells and its mechanism of action. We found that AA upregulated the expression of growth differentiation factor 15 (GDF15), which had a protective effect on inflammation and tissue damage. Therefore, we investigated whether AA-induced OS in KGN cells upregulates GDF15 expression as an OS response.Through silencing of GDF15 and supplementation with recombinant GDF15 (rGDF15), we found that GDF15, expressed as an OS response, protected KGN cells against AA-induced OS effects, such as impairment of secretory and mitochondrial functions and apoptosis. Therefore, this study suggested that AA might induce OS in KGN cells and upregulate the expression of GDF15 as a response to OS.

摘要

多囊卵巢综合征(PCOS)是排卵性不孕的主要原因,也是育龄妇女常见的生殖内分泌疾病。此外,近一半的 PCOS 患者与肥胖有关,他们的总游离脂肪酸往往会增加。花生四烯酸(AA)是一种多不饱和脂肪酸。AA 与各种酶(环氧化酶(COX)、脂氧合酶(LOX)、细胞色素 P450s(CYP))反应的氧化产物可以改变细胞线粒体的分布和钙离子浓度,并增加活性氧(ROS)的产生。在本研究中,我们分析了卵泡液中的脂肪酸,发现 PCOS 患者的 C20:4n6(AA)水平高于正常对照组。此外,为了确定 AA 是否会在人卵巢颗粒细胞瘤系(KGN)中诱导氧化应激(OS)并影响其功能,我们用或不用还原型谷胱甘肽(GSH)处理 KGN 细胞,然后用 AA 刺激它们。结果表明,AA 显著降低了 KGN 细胞的总抗氧化能力(TAC)和抗氧化酶的活性,增加了 MDA、ROS 和超氧阴离子(O)的水平。此外,AA 还损害了 KGN 细胞的分泌和线粒体功能,并诱导其凋亡。我们进一步研究了 AA 在 KGN 细胞中影响的下游基因及其作用机制。我们发现 AA 上调了生长分化因子 15(GDF15)的表达,GDF15 对炎症和组织损伤有保护作用。因此,我们研究了 AA 是否通过诱导 KGN 细胞中的 OS 而上调 GDF15 表达作为 OS 反应。通过沉默 GDF15 并补充重组 GDF15(rGDF15),我们发现 GDF15 作为 OS 反应表达,可保护 KGN 细胞免受 AA 诱导的 OS 效应的影响,如分泌和线粒体功能障碍和凋亡。因此,本研究表明 AA 可能诱导 KGN 细胞中的 OS,并上调 GDF15 的表达作为 OS 反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/17507951bf71/fendo-13-865748-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/e8d68f57ec03/fendo-13-865748-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/176c56aa96d7/fendo-13-865748-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/9b672acf5d48/fendo-13-865748-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/37adbdf4998c/fendo-13-865748-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/f040fa6dbe6f/fendo-13-865748-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/ec16e5fec10d/fendo-13-865748-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/2637b3f352b5/fendo-13-865748-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/1120390a0d41/fendo-13-865748-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/aa51fa7927e6/fendo-13-865748-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/2bfae412cf5f/fendo-13-865748-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/17507951bf71/fendo-13-865748-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/e8d68f57ec03/fendo-13-865748-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/176c56aa96d7/fendo-13-865748-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/9b672acf5d48/fendo-13-865748-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/37adbdf4998c/fendo-13-865748-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/f040fa6dbe6f/fendo-13-865748-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/ec16e5fec10d/fendo-13-865748-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/2637b3f352b5/fendo-13-865748-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/1120390a0d41/fendo-13-865748-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/aa51fa7927e6/fendo-13-865748-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/2bfae412cf5f/fendo-13-865748-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47da/9132262/17507951bf71/fendo-13-865748-g011.jpg

相似文献

1
Arachidonic Acid in Follicular Fluid of PCOS Induces Oxidative Stress in a Human Ovarian Granulosa Tumor Cell Line (KGN) and Upregulates GDF15 Expression as a Response.多囊卵巢综合征患者滤泡液中的花生四烯酸诱导人卵巢颗粒细胞瘤细胞系(KGN)氧化应激,并作为一种应对方式上调 GDF15 的表达。
Front Endocrinol (Lausanne). 2022 May 11;13:865748. doi: 10.3389/fendo.2022.865748. eCollection 2022.
2
Corrigendum: Arachidonic acid in follicular fluid of PCOS induces oxidative stress in a human ovarian granulosa tumor cell line (KGN) and upregulates GDF15 expression as a response.勘误:多囊卵巢综合征患者卵泡液中的花生四烯酸可诱导人卵巢颗粒细胞瘤细胞系(KGN)产生氧化应激,并上调生长分化因子15(GDF15)的表达作为一种反应。
Front Endocrinol (Lausanne). 2022 Oct 4;13:988767. doi: 10.3389/fendo.2022.988767. eCollection 2022.
3
GIMAP7 induces oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome by inhibiting sonic hedgehog signalling pathway.GIMAP7 通过抑制 sonic hedgehog 信号通路诱导多囊卵巢综合征患者卵巢颗粒细胞发生氧化应激和凋亡。
J Ovarian Res. 2022 Dec 30;15(1):141. doi: 10.1186/s13048-022-01092-z.
4
YKL-40 Knockdown Decreases Oxidative Stress Damage in Ovarian Granulosa Cells.YKL-40 敲低减少卵巢颗粒细胞的氧化应激损伤。
Genet Test Mol Biomarkers. 2024 May;28(5):199-206. doi: 10.1089/gtmb.2023.0361. Epub 2024 Apr 18.
5
Dopamine in human follicular fluid is associated with cellular uptake and metabolism-dependent generation of reactive oxygen species in granulosa cells: implications for physiology and pathology.人卵泡液中的多巴胺与颗粒细胞中细胞摄取和代谢依赖性活性氧生成有关:对生理学和病理学的影响。
Hum Reprod. 2014 Mar;29(3):555-67. doi: 10.1093/humrep/det422. Epub 2013 Nov 27.
6
The Release of Peripheral Immune Inflammatory Cytokines Promote an Inflammatory Cascade in PCOS Patients Altering the Follicular Microenvironment.外周免疫炎症细胞因子的释放促进 PCOS 患者的炎症级联反应,改变卵泡微环境。
Front Immunol. 2021 May 17;12:685724. doi: 10.3389/fimmu.2021.685724. eCollection 2021.
7
IL-15 Participates in the Pathogenesis of Polycystic Ovary Syndrome by Affecting the Activity of Granulosa Cells.IL-15 通过影响颗粒细胞的活性参与多囊卵巢综合征的发病机制。
Front Endocrinol (Lausanne). 2022 Feb 18;13:787876. doi: 10.3389/fendo.2022.787876. eCollection 2022.
8
Follicular fluid-derived exosomal miR-143-3p/miR-155-5p regulate follicular dysplasia by modulating glycolysis in granulosa cells in polycystic ovary syndrome.卵泡液来源的外泌体 miR-143-3p/miR-155-5p 通过调节多囊卵巢综合征颗粒细胞中的糖酵解来调节卵泡发育异常。
Cell Commun Signal. 2022 May 9;20(1):61. doi: 10.1186/s12964-022-00876-6.
9
Chitosan oligosaccharide improves ovarian granulosa cells inflammation and oxidative stress in patients with polycystic ovary syndrome.壳寡糖可改善多囊卵巢综合征患者卵巢颗粒细胞炎症和氧化应激。
Front Immunol. 2023 Mar 1;14:1086232. doi: 10.3389/fimmu.2023.1086232. eCollection 2023.
10
Elevated Levels of Follicular Fatty Acids Induce Ovarian Inflammation via ERK1/2 and Inflammasome Activation in PCOS.多囊卵巢综合征中,滤泡内脂肪酸水平升高通过 ERK1/2 和炎性小体激活诱导卵巢炎症。
J Clin Endocrinol Metab. 2022 Jul 14;107(8):2307-2317. doi: 10.1210/clinem/dgac281.

引用本文的文献

1
Microbial metabolites short chain fatty acids, tight junction, gap junction, and reproduction: a review.微生物代谢产物短链脂肪酸、紧密连接、间隙连接与生殖:综述
Front Cell Dev Biol. 2025 Aug 22;13:1624415. doi: 10.3389/fcell.2025.1624415. eCollection 2025.
2
Reactive oxygen species in polycystic ovary syndrome: Mechanistic insights into pathogenesis and therapeutic opportunities.多囊卵巢综合征中的活性氧:发病机制及治疗机会的机制性见解
Redox Biol. 2025 Jul 17;85:103776. doi: 10.1016/j.redox.2025.103776.
3
Feedback Regulation of sPLA2-COX/5-LOX-Ca2+ in Seminal Plasma and Its Impact on Sperm Quality Parameters.

本文引用的文献

1
Myricetin protects against H O -induced oxidative damage and apoptosis in bovine mammary epithelial cells.杨梅素可防止 H₂O₂诱导的奶牛乳腺上皮细胞氧化损伤和凋亡。
J Cell Physiol. 2021 Apr;236(4):2684-2695. doi: 10.1002/jcp.30035. Epub 2020 Sep 3.
2
Antibody-mediated inhibition of GDF15-GFRAL activity reverses cancer cachexia in mice.抗体介导的 GDF15-GFRAL 活性抑制可逆转小鼠癌症恶病质。
Nat Med. 2020 Aug;26(8):1264-1270. doi: 10.1038/s41591-020-0945-x. Epub 2020 Jul 13.
3
Recent advances in functional analysis of polyunsaturated fatty acid synthases.
精浆中sPLA2-COX/5-LOX-Ca2+的反馈调节及其对精子质量参数的影响
J Inflamm Res. 2025 Jun 13;18:7381-7400. doi: 10.2147/JIR.S523172. eCollection 2025.
4
Plumbagin ameliorates ferroptosis of ovarian granulosa cells in polycystic ovary syndrome by down-regulating SLC7A5 m6A methylation modification through inhibition of YTHDF1.白花丹醌通过抑制YTHDF1下调SLC7A5的m6A甲基化修饰,改善多囊卵巢综合征中卵巢颗粒细胞的铁死亡。
J Ovarian Res. 2025 Jun 2;18(1):115. doi: 10.1186/s13048-025-01700-8.
5
Granulosa cell RNA-Seq insights into senescence and sphingolipid metabolism disorder in PCOS: aspirin as a potential therapeutic drug.颗粒细胞RNA测序揭示多囊卵巢综合征中的衰老和鞘脂代谢紊乱:阿司匹林作为一种潜在的治疗药物
Reprod Biol Endocrinol. 2025 Apr 26;23(1):61. doi: 10.1186/s12958-025-01396-x.
6
Mechanisms of Granulosa Cell Programmed Cell Death and Follicular Atresia in Polycystic Ovary Syndrome.多囊卵巢综合征中颗粒细胞程序性细胞死亡与卵泡闭锁的机制
Physiol Res. 2025 Mar 21;74(1):31-40. doi: 10.33549/physiolres.935485.
7
Oxidative stress and energy metabolism abnormalities in polycystic ovary syndrome: from mechanisms to therapeutic strategies.多囊卵巢综合征中的氧化应激与能量代谢异常:从机制到治疗策略
Reprod Biol Endocrinol. 2024 Dec 26;22(1):159. doi: 10.1186/s12958-024-01337-0.
8
Unraveling the complexity of follicular fluid: insights into its composition, function, and clinical implications.揭开卵泡液的复杂性:解析其组成、功能及临床意义。
J Ovarian Res. 2024 Nov 26;17(1):237. doi: 10.1186/s13048-024-01551-9.
9
The association between dietary obesity-prevention score (DOS) and polycystic ovary syndrome: a case-control study.饮食肥胖预防评分(DOS)与多囊卵巢综合征的关联:一项病例对照研究。
Sci Rep. 2024 Nov 19;14(1):28618. doi: 10.1038/s41598-024-80238-z.
10
GDF-15 levels in patients with polycystic ovary syndrome treated with metformin: a combined clinical and in silico pathway analysis.多囊卵巢综合征患者经二甲双胍治疗后的 GDF-15 水平:一项联合临床和计算机途径分析。
Arch Endocrinol Metab. 2024 Aug 27;68:e230416. doi: 10.20945/2359-4292-2023-0416. eCollection 2024.
多不饱和脂肪酸合酶功能分析的最新进展。
Curr Opin Chem Biol. 2020 Dec;59:30-36. doi: 10.1016/j.cbpa.2020.04.015. Epub 2020 May 19.
4
Comprehensive Proteomics Analysis of Stressed Human Islets Identifies GDF15 as a Target for Type 1 Diabetes Intervention.应激状态下人胰岛的全面蛋白质组学分析鉴定 GDF15 为 1 型糖尿病干预靶点。
Cell Metab. 2020 Feb 4;31(2):363-374.e6. doi: 10.1016/j.cmet.2019.12.005. Epub 2020 Jan 9.
5
GDF15 Is an Inflammation-Induced Central Mediator of Tissue Tolerance.GDF15 是炎症诱导的组织耐受的中枢介质。
Cell. 2019 Aug 22;178(5):1231-1244.e11. doi: 10.1016/j.cell.2019.07.033. Epub 2019 Aug 8.
6
Metabolic syndrome in polycystic ovary syndrome: a systematic review, meta-analysis and meta-regression.多囊卵巢综合征中的代谢综合征:系统评价、荟萃分析和荟萃回归。
Obes Rev. 2019 Feb;20(2):339-352. doi: 10.1111/obr.12762. Epub 2018 Oct 19.
7
Cytotoxicity induced by fine particulate matter (PM) via mitochondria-mediated apoptosis pathway in human cardiomyocytes.细颗粒物 (PM) 通过线粒体介导的细胞凋亡途径诱导人心肌细胞的细胞毒性。
Ecotoxicol Environ Saf. 2018 Oct;161:198-207. doi: 10.1016/j.ecoenv.2018.05.092. Epub 2018 Jun 6.
8
Luteinizing Hormone Facilitates Antral Follicular Maturation and Survival via Thecal Paracrine Signaling in Cattle.黄体生成素通过牛卵巢膜旁旁分泌信号促进腔前卵泡的成熟和存活。
Endocrinology. 2018 Jun 1;159(6):2337-2347. doi: 10.1210/en.2018-00123.
9
Systematic evaluation of phenolic compounds and protective capacity of a new mulberry cultivar J33 against palmitic acid-induced lipotoxicity using a simulated digestion method.采用模拟消化法系统评价新型桑品种 J33 中酚类化合物及其对棕榈酸诱导的脂毒性的保护作用。
Food Chem. 2018 Aug 30;258:43-50. doi: 10.1016/j.foodchem.2018.03.049. Epub 2018 Mar 13.
10
Alterations of polyunsaturated fatty acid metabolism in ovarian tissues of polycystic ovary syndrome rats.多囊卵巢综合征大鼠卵巢组织中多不饱和脂肪酸代谢的改变。
J Cell Mol Med. 2018 Jul;22(7):3388-3396. doi: 10.1111/jcmm.13614. Epub 2018 Mar 30.