您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报 (医学版) ›› 2019, Vol. 57 ›› Issue (2): 75-79.doi: 10.6040/j.issn.1671-7554.0.2018.831

• 临床医学 • 上一篇    

多囊卵巢综合征患者颗粒细胞叉头框蛋白O1 mRNA的表达与意义

贺婷婷,刘昕,刘洪彬,赵世刚,张秀清,刘庆庆,游力,石玉华   

  1. 山东大学附属生殖医院 国家辅助生殖与优生工程技术研究中心 生殖内分泌教育部重点实验室 山东省生殖健康临床医学研究中心, 山东 济南 250001
  • 发布日期:2022-09-27
  • 通讯作者: 游力. E-mail:youlijn@126.com
  • 基金资助:
    国家重点研发计划(2017YFC1001004);国家自然科学基金(81471428);泰山学者工程专项经费(ts201712103)

Expression of Forkhead box protein O1 mRNA in granulosa cells of polycystic ovary sydrome patients and its significance

HE Tingting, LIU Xin, LIU Hongbin, ZHAO Shigang, ZHANG Xiuqing, LIU Qingqing, YOU Li, SHI Yuhua   

  1. Center for Reproductive Medicine, Shandong University;
    National Research Center for Assisted Reproductive Technology and Reproductive Genetics;
    The Key Laboratory of Reproductive Endocrinology(Shandong University), Ministry of Education;
    Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Jinan 250001, Shandong, China
  • Published:2022-09-27

摘要: 目的 探讨转录因子叉头框蛋白O1(FOXO1)在多囊卵巢综合征(PCOS)患者卵巢颗粒细胞中的表达及意义。 方法 采用逆转录实时定量PCR(qRT-PCR)检测67例PCOS患者(PCOS组)与63例对照患者(对照组)卵巢颗粒细胞中FOXO1的表达,并分析其临床意义。 结果 PCOS组的体质量指数(BMI)、胰岛素抵抗指数(HOMA-IR)、黄体生成素(LH)、睾酮(T)、抗苗勒氏管激素(AMH)、卵巢基础卵泡数(AFC)明显高于对照组(P均<0.05),但PCOS组的卵泡刺激素(FSH)低于对照组(P<0.05)。与对照患者相比,FOXO1在 PCOS患者卵巢颗粒细胞中的表达下降(P<0.05)。采用二元Logistic回归分析发现,FOXO1、AFC、HOMA-IR是影响PCOS的危险因素(P<0.05)。 结论 FOXO1在PCOS患者卵巢颗粒细胞低表达,可能在PCOS的发生发展中发挥重要作用。

关键词: 多囊卵巢综合征, 颗粒细胞, 叉头框蛋白O1

Abstract: Objective To explore the expression and significance of Forkhead box protein O1(FOXO1)in ovarian granulosa cells of patients suffering from polycystic ovary syndrome(PCOS). Methods A total of 130 patients, including 67 PCOS patients and 63 controls, were enrolled. The expression of FOXO1 in ovarian granulosa cells was examined by real-time quantitative reverse transcription PCR(qRT-PCR), and the clinical significance was analyzed. Results PCOS patients had significantly higher body mass index(BMI), homeostasis model assessment-insulin resistance(HOMA-IR), luteotropic hormone(LH), testosterone(T), anti-Mullerian hormone(AMH), average follicle count(AFC)levels(all P<0.05), but lower FSH level(P<0.05)than controls. Compared with controls, the expression of FOXO1 was much lower in granulosa cells of PCOS patients(P<0.05). Binary Logistic regression analysis revealed that FOXO1, AFC and HOMA-IR were risk factors influencing the occurrence of PCOS(P<0.05). Conclusion The lower expression of FOXO1 in the granulosa cells of PCOS patients may play an important role in the occurrence and development of PCOS.

Key words: Polycystic ovary syndrome, Granulosa cell, Forkhead box protein O1

中图分类号: 

  • R711.75
[1] Goodarzi MO, Dumesic DA, Chazenbalk G, et al. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis[J]. Nat Rev Endocrinol, 2011, 7(4): 219-231.
[2] Webber LJ, Stubbs S, Stark J, et al. Formation and early development of follicles in the polycystic ovary[J]. Lancet, 2003, 362(9389): 1017-1021.
[3] Maciel GA, Baracat EC, Benda JA, et al. Stockpiling of transitional and classic primary follicles in ovaries of women with polycystic ovary syndrome[J]. J Clin Endocrinol Metab, 2004, 89(11): 5321-5327.
[4] Das M, Djahanbakhch O, Hacihanefioglu B, et al. Granulosa cell survival and proliferation are altered in polycystic ovary syndrome[J]. J Clin Endocrinol Metab, 2008, 93(3): 881-887.
[5] Stubbs SA, Stark J, Dilworth SM, et al. Abnormal preantral folliculogenesis in polycystic ovaries is associated with increased granulosa cell division[J]. J Clin Endocrinol Metab, 2007, 92(11): 4418-4426.
[6] Webber LJ, Stubbs SA, Stark J, et al. Prolonged survival in culture of preantral follicles from polycystic ovaries[J]. J Clin Endocrinol Metab, 2007, 92(5): 1975-1978.
[7] Song HM, Song JL, Li DF, et al. Inhibition of FOXO1 by small interfering RNA enhances proliferation and inhibits apoptosis of papillary thyroid carcinoma cells via Akt/FOXO1/Bim pathway[J]. Onco Targets Ther, 2015, 8: 3565-3573. doi: 10.2147/OTT.S95395.
[8] Prasad SB, Yadav SS, Das M, et al. Down regulation of FOXO1 promotes cell proliferation in cervical cancer[J]. J Cancer, 2014, 5(8): 655-662.
[9] He W, Lin F, Xia D, et al. MiR-374a promotes the proliferation of human osteosarcoma by downregulating FOXO1 expression[J]. Int J Clin Exp Med, 2014, 8(3): 3482-3489.
[10] Shi F, LaPolt PS. Relationship between FoxO1 protein levels and follicular development, atresia, and luteinization in the rat ovary[J]. J Endocrinol, 2003, 179(2): 195-203.
[11] Richards JS, Sharma SC, Falender AE, et al. Expression of FKHR, FKHRL1, and AFX genes in the rodent ovary: evidence for regulation by IGF-I, estrogen, and the gonadotropins[J]. Mol Endocrinol, 2002, 16(3): 580-599.
[12] Cunningham MA, Zhu Q, Unterman TG, et al. Follicle-stimulating hormone promotes nuclear exclusion of the forkhead transcription factor FoxO1a via phosphatidylinositol 3-kinase in porcine granulosa cells[J]. Endocrinology, 2003, 144(12): 5585-5594.
[13] Gebremedhn S, Salilewwondim D, Hoelker M, et al. MicroRNA-183-96-182 cluster regulates bovine granulosa cell proliferation and cell cycle transition by coordinately targeting FOXO1[J]. Biol Reprod, 2016, 94(6): 127. doi: 10.1095/biolreprod.115.137539.
[14] 夏雅仙.多囊卵巢综合征(PCOS)诊断—中华人民共和国卫生行业标准[S]. 2012 浙江省计划生育与生殖医学学术年会论文集[C]. 2012: 130-137.
[15] 贾月月,刘洪彬,李婧博,等.多囊卵巢综合征患者颗粒细胞microRNA-200b的表达及影响[J].山东大学学报(医学版), 2017, 55(1): 63-68. JIA Yueyue, LIU Hongbin, LI Jingbo, et al. Expression of microRNA-200b in granulosa cells of PCOS patients and its significance[J]. Journal of Shandong University(Health Sciences), 2017, 55(1): 63-68.
[16] Sanchez AM, Candau RB, Bernardi H. FoxO transcription factors: their roles in the maintenance of skeletal muscle homeostasis[J]. Cell Mol Life Sci, 2014, 71(9): 1657-1671.
[17] Anderson MJ, Viars CS, Czekay S, et al. Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily[J]. Genomics, 1998, 47(2): 187-199.
[18] Sumarac-Dumanovic M, Apostolovic M, Janjetovic K, et al. Downregulation of autophagy gene expression in endometria from women with polycystic ovary syndrome[J]. Mol Cell Endocrinol, 2017, 440: 116-124. doi: 10.1016/j.mce.2016.11.009.
[19] Lan ZJ, Krause MS, Redding SD, et al. Selective deletion of Pten in theca-interstitial cells leads to androgen excess and ovarian dysfunction in mice[J]. Mol Cell Endocrinol, 2017, 444: 26-37. doi: 10.1016/j.mce.2017.01.043.
[20] Kajihara T, Uchino S, Suzuki M, et al. Increased ovarian follicle atresia in obese Zucker rats is associated with enhanced expression of the forkhead transcription factor FOXO1[J]. Med Mol Morphol, 2009, 42(4): 216-221.
[21] Liu Z, Ren YA, Pangas SA, et al. FOXO1/3 and PTEN depletion in granulosa cells promotes ovarian granulosa cell tumor developmen[J]. Mol Endocrinol, 2015, 29(7): 1006-1024.
[22] Gebremedhn S, Salilew-Wondim D, Hoelker M, et al. MicroRNA-183-96-182 cluster regulates bovine granulosa cell proliferation and cell cycle transition by coordinately targeting FOXO1[J]. Biol Reprod, 2016, 94(6): 127. doi: 10.1095/biolreprod.115.137539.
[23] Shen M, Liu Z, Li B, et al. Involvement of FoxO1 in the effects of follicle-stimulating hormone on inhibition of apoptosis in mouse granulosa cells[J]. Cell Death Dis, 2014, 5: e1475-e1475. doi:10.1038/cddis.2014.400.
[24] Chang RJ, Cook-Andersen H. Disordered follicle development[J]. Mol Cell Endocrinol, 2013, 373(1-2): 51-60.
[25] Fang D, Huang Z, Guan H, et al. The Akt/FoxO1/p27 pathway mediates the proliferative action of liraglutide in beta cells[J]. Mol Med Rep, 2012, 5(1): 233-238.
[26] Han DF, Zhang JX, Wei WJ, et al. Fenofibrate induces G0/G1 phase arrest by modulating the PPARalpha/FoxO1/p27 kip pathway in human glioblastoma cells[J]. Tumour Biol, 2015, 36(5): 3823-3829.
[27] Alikhani M, Alikhani Z, Graves DT. FOXO1 functions as a master switch that regulates gene expression necessary for tumor necrosis factor-induced fibroblast apoptosis[J]. J Biol Chem, 2005, 280(13): 12096-12102.
[1] 虎娜,孙苗,邢莎莎,许丹霞,海小明,马玲,杨丽,勉昱琛,何瑞,陈冬梅,马会明. 月见草油抵抗多囊卵巢综合征大鼠卵巢氧化应激[J]. 山东大学学报 (医学版), 2022, 60(5): 22-30.
[2] 宋甜,付琳琳,王秋敏,杨晓,王莹,边月红,石玉华. 脂肪酸转运蛋白1在多囊卵巢综合征患者颗粒细胞中的表达[J]. 山东大学学报 (医学版), 2022, 60(2): 22-26.
[3] 牛群,石婧婧,符江. WNT5A基因对卵巢颗粒细胞胰岛素反应性和胰岛素抵抗的调控作用[J]. 山东大学学报 (医学版), 2021, 59(6): 57-63.
[4] 韩笑,李雷,刘聪聪. 睾酮对于多囊卵巢综合征易感基因Tox3表达的影响[J]. 山东大学学报 (医学版), 2021, 59(4): 42-47.
[5] 宫小舒, 吴日超, 李秀芳, 潘烨, 王泽, 石玉华. 603例多囊卵巢综合征患者不同促排卵内膜准备方案对冻胚移植结局的影响[J]. 山东大学学报 (医学版), 2021, 59(3): 48-54.
[6] 哈灵侠,殷婷,吴阳阳,黎维霞,杜玉冬. 多囊卵巢综合征患者中胰岛素抵抗与子宫内膜局部炎症因子及葡萄糖转运蛋白-4表达的相关性[J]. 山东大学学报 (医学版), 2021, 59(11): 41-47.
[7] 丁祥云,于清梅,张文芳,庄园,郝晶. 胰岛素样生长因子II在84例多囊卵巢综合征患者颗粒细胞中的表达和促排卵结局的相关性[J]. 山东大学学报 (医学版), 2020, 1(7): 60-66.
[8] 刘聪聪,刘洪彬,符江,李雷. 多囊卵巢综合征易感基因dennd1a在斑马鱼模型中的表达特性[J]. 山东大学学报 (医学版), 2019, 57(1): 48-54.
[9] 舒心,王群,黄涛,赵世刚,石玉华,刘洪彬. 多囊卵巢综合征高雄激素血症患者颗粒细胞FBP1基因的表达及影响[J]. 山东大学学报 (医学版), 2018, 56(4): 58-63.
[10] 王玉红,张丽红,王林省,陈月芹,王彦辉,王皆欢,李传福. 消化道颗粒细胞瘤的影像学表现[J]. 山东大学学报(医学版), 2017, 55(8): 66-70.
[11] 张素萍,王泽,周亚丽, 李敬,路西兰,柏宏伟,石玉华. 来曲唑治疗不同体质量指数多囊卵巢综合征患者的临床效果[J]. 山东大学学报(医学版), 2017, 55(5): 81-85.
[12] 张琳,李敬,王泽,张江涛,马增香,石玉华. 多囊卵巢综合征患者促甲状腺激素对血糖、血脂的影响[J]. 山东大学学报(医学版), 2017, 55(1): 80-84.
[13] 李婧博,刘洪彬,贾月月,王泽,孙梅,石玉华. microRNA-183在PCOS胰岛素抵抗中的表达及其临床意义[J]. 山东大学学报(医学版), 2017, 55(1): 69-74.
[14] 贾月月,刘洪彬,李婧博,李敬,张江涛, 孙梅,石玉华. 多囊卵巢综合征患者颗粒细胞microRNA-200b的表达及影响[J]. 山东大学学报(医学版), 2017, 55(1): 63-68.
[15] 杨冬梓,麦卓瑶. 高龄多囊卵巢综合征患者的卵巢储备特点及其助孕结局[J]. 山东大学学报(医学版), 2017, 55(1): 26-32.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!