HDAC5 inhibits ovarian angiogenesis in dehydroepiandrosterone-induced mouse model of polycystic ovary syndrome

被引:3
作者
Wang, Ying [1 ]
Wang, Yu [2 ]
Chen, Yao [2 ]
Gao, Qianqian [2 ]
Hou, Lihui [1 ]
Feng, Xiaoling [1 ]
机构
[1] Heilongjiang Univ Chinese Med, Affiliated Hosp 1, Dept Gynecol 2, 26 Heping Rd, Harbin, Peoples R China
[2] Heilongjiang Univ Chinese Med, Grad Sch, Harbin, Peoples R China
基金
中国国家自然科学基金;
关键词
mouse; polycystic ovary syndrome; HDAC5; overexpression; angiogenesis; oxidative stress; ENDOTHELIAL GROWTH-FACTOR; FOLLICULAR DEVELOPMENT; OXIDATIVE STRESS; RAT MODEL; EXPRESSION; GENE; RESISTANCE;
D O I
10.5603/FHC.a2022.0024
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Introduction. Abnormal ovarian angiogenesis is a common feature of polycystic ovary syndrome (PCOS), a typical endocrine disorder affecting women of reproductive age. Histone deacetylase 5 (HDAC5) has been documented as a suppressor of angiogenesis. The aim of this study was to explore the effect of HDAC5 on ovarian angiogenesis in a PCOS mouse model. Material and methods. PCOS was induced in female C57BL/6 mice by 20-day administration of dehydroepiandrosterone (DHEA). HDAC5 was over-expressed in PCOS mice by corresponding adenovirus injection. In total, 120 mice were used in this study. Western-blotting, real-time PCR, hematoxylin and eosin staining, enzyme-linked immunosorbent assay (ELISA), immunohistochemical staining, flow cytometry, and co-immunoprecipitation were respectively used to evaluate the effect of HDAC5 on PCOS mice. Results. PCOS ovaries showed a compensatory increase in HDAC5 expression, while HDAC5 over-expression alleviated abnormalities in ovarian morphology and serum hormone levels after PCOS modeling. HDAC5 inhibited ovarian angiogenesis in PCOS mice by regulating angiogenesis-related factors, such as VEGFA, platelet-derived growth factors B and D (PDGFB/D), and angiopoietins 1 and 2 (ANGPT1/2) and CD31. HDAC5 over-expression decreased levels of reactive oxygen species (ROS) and malondialdehyde, while promoting activities of catalase and superoxide dismutase in ovaries of PCOS mice, suggesting its suppressive effects on oxidative stress, an inducer of uncontrolled angiogenesis. Moreover, HDAC5 suppressed activation of angiogenesis-related HIF-1a/VEGFA/VEGFR2 signaling in PCOS ovaries partly via inhibiting VEGFR2 acetylation. Conclusions. This study reveals the protective role of HDAC5 in PCOS by inhibiting ovarian angiogenesis and provides a molecular candidate for PCOS therapy in the future.
引用
收藏
页码:260 / 270
页数:11
相关论文
共 50 条
  • [21] MiR-185-5p Protects Against Angiogenesis in Polycystic Ovary Syndrome by Targeting VEGFA
    Wei, Jingzan
    Zhao, Yanyan
    FRONTIERS IN PHARMACOLOGY, 2020, 11
  • [22] Yogurt Enriched with Inulin Ameliorated Reproductive Functions and Regulated Gut Microbiota in Dehydroepiandrosterone-Induced Polycystic Ovary Syndrome Mice
    Li, Tiange
    Zhang, Yue
    Song, Jiajia
    Chen, Lijun
    Du, Min
    Mao, Xueying
    NUTRIENTS, 2022, 14 (02)
  • [23] Beneficial effects of apigenin on ovarian histological changes and angiogenesis gene expression in rat model of polycystic ovary syndrome
    Samani, Sanaz Lotfi
    Yadi, Mahsa
    Aflatoonian, Behrouz
    Zarehmehrjerdi, Fatemeh
    Hafizibarjin, Zeynab
    Rezvani, Mohammad Ebrahim
    Izadi, Mahin
    NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2024, : 2641 - 2649
  • [24] The ameliorative effects of marjoram in dehydroepiandrosterone induced polycystic ovary syndrome in rats
    Rababa'h, Abeer M.
    Matani, Bayan R.
    Ababneh, Mera A.
    LIFE SCIENCES, 2020, 261
  • [25] Chinese medicine compound prescription HeQi San ameliorates chronic inflammatory states and modulates gut flora in dehydroepiandrosterone-induced polycystic ovary syndrome mouse model
    Li, Juntong
    Liu, Deliang
    Zhao, Hengxia
    Zhang, Pengxiang
    Cai, Fangying
    Li, Huilin
    Chu, Shufang
    INTERNATIONAL IMMUNOPHARMACOLOGY, 2024, 137
  • [26] Korean Red Ginseng alleviates dehydroepiandrosterone-induced polycystic ovarian syndrome in rats via its antiinflammatory and antioxidant activities
    Choi, Jong Hee
    Jang, Minhee
    Kim, Eun-Jeong
    Lee, Min Jung
    Park, Kyoung Sun
    Kim, Seung-Hyun
    In, Jun-Gyo
    Kwak, Yi-Seong
    Park, Dae-Hun
    Cho, Seung-Sik
    Nah, Seung-Yeol
    Cho, Ik-Hyun
    Bae, Chun-Sik
    JOURNAL OF GINSENG RESEARCH, 2020, 44 (06) : 790 - 798
  • [27] Lysyl oxidase and MMP-2 expression in dehydroepiandrosterone-induced polycystic ovary in rats
    Henmi, H
    Endo, T
    Nagasawa, K
    Hayashi, T
    Chida, M
    Akutagawa, N
    Iwasaki, M
    Kitajima, Y
    Kiya, T
    Nishikawa, A
    Manase, K
    Kudo, R
    BIOLOGY OF REPRODUCTION, 2001, 64 (01) : 157 - 162
  • [28] Endoplasmic Reticulum Stress in Myometrial Smooth Muscle Cells and Spontaneous Contraction Changes in the Uterus of Dehydroepiandrosterone-induced Polycystic Ovary Syndrome Rats
    Karagul, Meryem Ilkay
    Yildirim, Ayse
    Asoglu, Zehra Demiray
    Dogan, Serdar
    Aktas, Savas
    Un, Ismail
    Barlas, Ibrahim Omer
    CELL BIOCHEMISTRY AND BIOPHYSICS, 2025, 83 (01) : 893 - 904
  • [29] The anti-androgenic effect of quercetin on hyperandrogenism and ovarian dysfunction induced in a dehydroepiandrosterone rat model of polycystic ovary syndrome
    Mahmoud, Asmaa A.
    Elfiky, Asmaa M.
    Abo-Zeid, Faten S.
    STEROIDS, 2022, 177
  • [30] The effect of cinnamon on polycystic ovary syndrome in a mouse model
    Dou, Lei
    Zheng, Yahong
    Li, Lu
    Gui, Xiaowei
    Chen, Yajuan
    Yu, Meng
    Guo, Yi
    REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY, 2018, 16