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Vol 60, No 3 (2022)
Original paper
Submitted: 2022-05-15
Accepted: 2022-08-17
Published online: 2022-09-16
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HDAC5 inhibits ovarian angiogenesis in dehydroepiandrosterone-induced mouse model of polycystic ovary syndrome

Ying Wang1, Yu Wang2, Yao Chen2, Qianqian Gao2, Lihui Hou1, Xiaoling Feng1
DOI: 10.5603/FHC.a2022.0024
·
Pubmed: 36124413
·
Folia Histochem Cytobiol 2022;60(3):260-270.
Affiliations
  1. The Second Department of Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
  2. Graduate School, Heilongjiang University of Chinese Medicine, Harbin, China

open access

Vol 60, No 3 (2022)
ORIGINAL PAPERS
Submitted: 2022-05-15
Accepted: 2022-08-17
Published online: 2022-09-16

Abstract

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-1α/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.

Abstract

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-1α/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.

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Keywords

mouse; polycystic ovary syndrome; HDAC5 overexpression; angiogenesis; oxidative stress

About this article
Title

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

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 60, No 3 (2022)

Article type

Original paper

Pages

260-270

Published online

2022-09-16

Page views

4574

Article views/downloads

831

DOI

10.5603/FHC.a2022.0024

Pubmed

36124413

Bibliographic record

Folia Histochem Cytobiol 2022;60(3):260-270.

Keywords

mouse
polycystic ovary syndrome
HDAC5 overexpression
angiogenesis
oxidative stress

Authors

Ying Wang
Yu Wang
Yao Chen
Qianqian Gao
Lihui Hou
Xiaoling Feng

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