Volume 20 Issue 11
Nov.  2022
Turn off MathJax
Article Contents
Article Navigation >  Chinese Journal of General Practice  > 2022  >  20(11): 1836-1840
YU Xiao-yan, WANG Lie-hong, YANG Hui-lin, MA Ying-lan, LI Yan-zi. Role of EZH2 in endometriosis-related infertility induced by oxidative stress in ovarian granulosa cells[J]. Chinese Journal of General Practice, 2022, 20(11): 1836-1840. doi: 10.16766/j.cnki.issn.1674-4152.002714
Citation: YU Xiao-yan, WANG Lie-hong, YANG Hui-lin, MA Ying-lan, LI Yan-zi. Role of EZH2 in endometriosis-related infertility induced by oxidative stress in ovarian granulosa cells[J]. Chinese Journal of General Practice, 2022, 20(11): 1836-1840. doi: 10.16766/j.cnki.issn.1674-4152.002714
shu

Role of EZH2 in endometriosis-related infertility induced by oxidative stress in ovarian granulosa cells

doi: 10.16766/j.cnki.issn.1674-4152.002714

  • Department of Reproductive Center, Qinghai Red Cross Hospital, Xining, Qinghai 810000, China

Funds:

 2019-q-051

  • Received Date: 2021-09-03
    Available Online: 2022-12-30
    Abstract
  •   Objective  To explore the role of enhancer of Zeste homologue 2 (EZH2) in ovarian granulosa cells (GCs) and oxidative stress (OS)-induced infertility related to endometriosis (EM).  Methods  The GCs were collected from 66 patients with deep invasive EM and 63 patients with tubal infertility (control group) in the Department of Reproductive Medicine, Qinghai Red Cross Hospital from April 2019 to November 2020. Flow cytometry was used in analysing the level of ROS in GCs. The COV434 cell model with low EZH2 expression was established in vitro and treated with H2O2. Cell senescence was measured by SA-β-gal. A mouse EM model was established, treated with an intraperitoneal injection of the EZH2 inhibitor DZNep and subjected to 6-month fertility test.  Results  Compared with the control group, the chronic pelvic pain score, dysmenorrhea pain score and serum CA-125 antigen significantly increased in the EM group (all P < 0.001), and the number of cells, average number of 2 PN embryos, average number of high-quality embryos and clinical pregnancy rate per embryo transfer cycle significantly decreased (all P < 0.001). Compared with control GCs, the intracellular ROS in GCs of patients with EM increased significantly (3.62±0.26 vs. 12.25±0.74, P < 0.001), and the expression levels of iNOS and SOD1 in the GCs decreased significantly (all P < 0.05). EZH2 knockdown significantly reversed H2O2-induced increase in ROS levels and SA-β-Gal activity (all P < 0.05) and down-regulated the expression of senescence-related proteins (all P < 0.05). The EM lesions in the EM+DZNep group was significantly smaller than those in the EM group [(433±74) mm3 vs. (1 624±182)mm3, P < 0.001], and the mean number of pups per delivery was significantly greater than in the EM group (all P < 0.05).  Conclusion  EZH2 is involved in EM-related infertility induced by GC cell OS.

     

    • FullText(HTML)
  • loading
    • References(20)
  • [1]
    钟方圆, 罗金, 谢青贞. 子宫内膜异位症性不孕的研究进展[J]. 中华生殖与避孕杂志, 2019, 39(7): 592-595. https://www.cnki.com.cn/Article/CJFDTOTAL-AMYD202214020.htm

    ZHONG F Y, LUO J, XIE Q Z. Progress of endometriosis-associated infertility[J]. Chinese Journal of Reproduction and Contraception, 2019, 39(7): 592-595. https://www.cnki.com.cn/Article/CJFDTOTAL-AMYD202214020.htm
    [2]
    FERRERO H, CORACHÁN A, AGUILAR A, et al. Single-cell RNA sequencing of oocytes from ovarian endometriosis patients reveals a differential transcriptomic profile associated with lower quality[J]. Hum Reprod, 2019, 34(7): 1302-1312. doi: 10.1093/humrep/dez053
    [3]
    郭琴, 骆婕, 廖凤儿, 等. FBW7通过促进NOX1降解抑制ox-LDL诱导的颗粒细胞凋亡[J]. 中国病理生理杂志, 2020, 36(12): 2234-2243. doi: 10.3969/j.issn.1000-4718.2020.12.016

    GUO Q, LUO J, LIAO F E, et al. FBW7 inhibits ox-LDL-induced granulosa cell apoptosis by promoting NOX1 degradation[J]. Chinese Journal of Pathophysiology, 2020, 36(12): 2234-2243. doi: 10.3969/j.issn.1000-4718.2020.12.016
    [4]
    王莉萍, 孙祖越. 抗氧化剂拮抗子宫内膜异位症的研究进展[J]. 中国比较医学杂志, 2019, 29(10): 131-135. doi: 10.3969/j.issn.1671-7856.2019.10.023

    WANG L P, SUN Z Y. Progress in research on the effects of antioxidants on endometriosis[J]. Chinese Journal of Comparative Medicine, 2019, 29(10): 131-135. doi: 10.3969/j.issn.1671-7856.2019.10.023
    [5]
    ZHANG L Y, WANG Z C, LU T F, et al. Mitochondrial Ca2+ overload leads to mitochondrial oxidative stress and delayed meiotic resumption in mouse oocytes[J]. Front Cell Dev Biol, 2020, 8: 1053.
    [6]
    WAN S S, PAN Y M, YANG W J, et al. Inhibition of EZH2 alleviates angiogenesis in a model of corneal neovascularization by blocking FoxO3a-mediated oxidative stress[J]. FASEB J, 2020, 34(8): 10168-10181. doi: 10.1096/fj.201902814RRR
    [7]
    HUO S W, QI H R, SI Y X, et al. MicroRNA 26a targets Ezh2 to regulate apoptosis in mouse ovarian granulosa cells[J]. Syst Biol Reprod Med, 2021, 67(3): 221-229. doi: 10.1080/19396368.2021.1895362
    [8]
    ZHANG Q Q, SUN H, ZHUANG S G, et al. Novel pharmacological inhibition of EZH2 attenuates septic shock by altering innate inflammatory responses to sepsis[J]. Int Immunopharmacol, 2019, 76: 105899. DOI: 10.1016/j.intimp.2019.105899.
    [9]
    赵嘉欣, 汤小晗, 卢美松. 氧化应激标志物与子宫内膜异位症的研究进展[J]. 中国计划生育和妇产科, 2020, 12(9): 5-7. https://www.cnki.com.cn/Article/CJFDTOTAL-JHFC202009002.htm

    ZHAO J X, TANG X H, LU M S. Research progress of oxidative stress markers and endometriosis[J]. Chinese Journal of Family Planning & Gynecotokology, 2020, 12(9): 5-7. https://www.cnki.com.cn/Article/CJFDTOTAL-JHFC202009002.htm
    [10]
    徐允剑, 金妲娜, 薛亚东. 月经周期各阶段不同中药方剂辅助治疗对多囊卵巢综合征不孕患者卵巢功能及妊娠的影响[J]. 中华全科医学, 2018, 16(4): 626-629. doi: 10.16766/j.cnki.issn.1674-4152.000173

    XU Y J, JIN D N, XUE Y D. Effects of different Chinese medicine prescriptions treating at different stages of menstrual cycle on ovarian function and pregnancy in infertile women with polycystic ovary syndrome[J]. Chinese Journal of General Practice, 2018, 16(4): 626-629. doi: 10.16766/j.cnki.issn.1674-4152.000173
    [11]
    LIM D W, PARK J, JUNG J, et al. Dicaffeoylquinic acids alleviate memory loss via reduction of oxidative stress in stress-hormone-induced depressive mice[J]. Pharmacol Res, 2020, 161: 105252. DOI: 10.1016/j.phrs.2020.105252.
    [12]
    陈波, 彭文勇, 屠文龙, 等. 右美托咪定对腹腔镜胃癌根治术患者氧化应激、糖代谢及术后镇痛的影响[J]. 中华全科医学, 2018, 16(3): 395-397, 451. doi: 10.16766/j.cnki.issn.1674-4152.000109

    CHEN B, PENG W Y, TU W L, et al. Effect of dexmedetomidine on oxidative stress, glycometabolism and postoperative analgesia in patients with laparoscopic radical gastrectomy[J]. Chinese Journal of General Practice, 2018, 16(3): 395-397, 451. doi: 10.16766/j.cnki.issn.1674-4152.000109
    [13]
    XU H T, MU X Y, DING Y B, et al. Melatonin alleviates benzo (a) pyrene-induced ovarian corpus luteum dysfunction by suppressing excessive oxidative stress and apoptosis[J]. Ecotoxicol Environ Saf, 2021, 207: 111561. DOI: 10.1016/j.ecoenv.2020.111561.
    [14]
    KHADRAWY O, GEBREMEDHN S, SALILEW-WONDIM D, et al. Endogenous and exogenous modulation of Nrf2 mediated oxidative stress response in bovine granulosa cells: Potential implication for ovarian function[J]. Int J Mol Sci, 2019, 20(7): 1635. doi: 10.3390/ijms20071635
    [15]
    LAI Q H, XIANG W P, LI Q, et al. Oxidative stress in granulosa cells contributes to poor oocyte quality and IVF-ET outcomes in women with polycystic ovary syndrome[J]. Front Med, 2018, 12(5): 518-524.
    [16]
    FRIESEN C R, NOBLE D W A, OLSSON M. The role of oxidative stress in postcopulatory selection[J]. Philos Trans R Soc Lond B Biol Sci, 2020, 375(1813): 20200065. DOI: 10.1098/rstb.2020.0065.
    [17]
    LIANG X R, YAN Z J, MA W W, et al. Peroxiredoxin 4 protects against ovarian ageing by ameliorating d-galactose-induced oxidative damage in mice[J]. Cell Death Dis, 2020, 11(12): 1053-1062.
    [18]
    丁祥云, 于清梅, 张文芳, 等. 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, 58(7): 60-66, 76. https://www.cnki.com.cn/Article/CJFDTOTAL-SDYB202007009.htm

    DING X Y, YU Q M, ZHANG W F, et al. Correlation of the expression of insulin-like growth factor Ⅱ in granulosa cells and ovulation induction outcomes of 84 patients with polycystic ovary syndrome[J]. Journal of Shandong University (Health Sciences), 2020, 58(7): 60-66, 76. https://www.cnki.com.cn/Article/CJFDTOTAL-SDYB202007009.htm
    [19]
    CHEN S Q, LI J Q, WANG X Q, et al. EZH2-inhibitor DZNep enhances apoptosis of renal tubular epithelial cells in presence and absence of cisplatin[J]. Cell Div, 2020, 15(1): 8.
    [20]
    LIU H, CHEN Z Y, WENG X D, et al. Enhancer of zeste homolog 2 modulates oxidative stress-mediated pyroptosis in vitro and in a mouse kidney ischemia-reperfusion injury model[J]. FASEB J, 2020, 34(1): 835-852.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(4)  / Tables(1)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (353) PDF downloads(9) Cited by()
    Proportional views
    Related

    Address：No. 287, Changhuai Road, Bengbu, Anhui Province, 233004, P.R.ChinaphoneNo：0552-3066635； 0552-3051890Email：zhqkyx@163.com

    Copyright © Chinese Journal of General Practice皖ICP备2020018345号-2

    Supported by: Beijing Renhe Information Technology Co., Ltd.    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return