Mechanism of estrogen downregulating hypoxia⁃inducible factor⁃1α to promote invasion and migration of endometriosis

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Mechanism of estrogen downregulating hypoxia⁃inducible factor⁃1α to promote invasion and migration of endometriosis

更新时间：2026-11-05

- Mechanism of estrogen downregulating hypoxia⁃inducible factor⁃1α to promote invasion and migration of endometriosis
- Medical Journal of Wuhan University Vol. 46, Issue 9, Pages: 1124-1129(2025)
- 作者机构：
  
  1.武汉市第四医院武胜路院区妇产科湖北武汉 430030
  2.湖北省妇幼保健院湖北武汉 430070
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.0181
  CLC： R71
- Received：16 March 2024，
  
  Published：26 September 2025
- 稿件说明：
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盛慧,常亚男,杨贵云等.雌激素下调低氧诱导因子⁃1α促进子宫内膜异位症侵袭和迁移的作用机制[J].武汉大学学报（医学版）,2025,46(09):1124-1129.

SHENG Hui,CHANG Yanan,YANG Guiyun,et al.Mechanism of estrogen downregulating hypoxia⁃inducible factor⁃1α to promote invasion and migration of endometriosis[J].Medical Journal of Wuhan University,2025,46(09):1124-1129.
盛慧,常亚男,杨贵云等.雌激素下调低氧诱导因子⁃1α促进子宫内膜异位症侵袭和迁移的作用机制[J].武汉大学学报（医学版）,2025,46(09):1124-1129. DOI： 10.14188/j.1671-8852.2024.0181.

SHENG Hui,CHANG Yanan,YANG Guiyun,et al.Mechanism of estrogen downregulating hypoxia⁃inducible factor⁃1α to promote invasion and migration of endometriosis[J].Medical Journal of Wuhan University,2025,46(09):1124-1129. DOI： 10.14188/j.1671-8852.2024.0181.

摘要

目的

2

探讨雌激素和低氧诱导因子⁃1α（HIF⁃1α）在子宫内膜异位病灶侵袭和迁移的作用和调控机制。

方法

2

将子宫内膜间质细胞（ESCs）分为3组，分别为oe⁃vector组（过表达vector质粒的ESCs），oe⁃HIF⁃1α组（转染了过表达HIF⁃1α质粒的ESCs），oe⁃HIF⁃1α+E

2

组[成功转染oe⁃HIF⁃1α质粒的ESCs后再用10

-8

mol·L

-1

17β⁃雌二醇(E

2

)处理

]

，检测ESCs侵袭和迁移能力以及上皮细胞⁃间质转化（EMT）相关分子E⁃Cadherin和Vimentin的表达水平。

结果

2

oe⁃HIF⁃1α+E

2

组ESCs中HIF⁃1α表达水平均低于oe⁃HIF⁃1α组和oe⁃vector组，且oe⁃HIF⁃1α组HIF⁃1α表达高于oe⁃vector组（均

P

<

0.05）；oe⁃HIF⁃1α+E

2

组ESCs侵袭迁移能力均高于oe⁃HIF⁃1α和oe⁃vector组，且oe⁃HIF⁃1α组ESCs侵袭迁移能力在3组中最低（均

P

<

0.05）；oe⁃HIF⁃1α+E

2

组E⁃Cadherin蛋白和mRNA水平均高于oe⁃HIF⁃1α和oe⁃vector组，且oe⁃HIF⁃1α组E⁃Cadherin蛋

白和mRNA水平的表达在3组中最低（均

P

<

0.05）。oe⁃HIF⁃1α+E

2

组Vimentin蛋白和mRNA水平均低于oe⁃HIF⁃1α和oe⁃vector组，且oe⁃HIF⁃1α组Vimentin蛋白和mRNA水平的表达在3组中最高（均

P

<

0.05）。

结论

2

E

2

可能是通过抑制HIF⁃1α促进子宫内膜细胞EMT过程从而促进异位的子宫内膜发生侵袭和转移，HIF⁃1α有望成为子宫内膜异位症治疗的靶点之一。

Abstract

Objective

2

To explore the roles and regulatory mechanisms of estrogen and hypoxia⁃inducible factor⁃1α(HIF⁃1α) in the invasion and migration of endometriosis lesions.

Methods

2

Endometrial stromal cells (ESCs) were divided into three groups： oe⁃vector group (overexpressing vector plasmid in ESCs)

oe⁃HIF⁃1 group (overexpressing vector plasmid in ESCs)

and oe⁃HIF⁃1α+E

2

group (overexpressing vector plasmid in ESCs and using 17β⁃Estradiol

E

2

). The invasion and migration ability of ESCs were evaluated

as well as the expression levels of epithelial⁃mesenchymal transition （EMT） related molecules E⁃Cadherin and Vimentin were determined.

Results

2

The expression of HIF⁃1α in the oe⁃HIF⁃1α+E

2

group was lower than that in oe⁃HIF⁃1 group and oe⁃vector group

and the expression of HIF⁃1α in oe⁃HIF⁃1 group was the highest (all

P

<

0.05). The invasion and migration ability of oe⁃HIF⁃1α+E

2

group was higher than that of oe⁃HIF⁃1α and oe⁃vector group

but the ability of oe⁃HIF⁃1α group was the lowest (

P

<

0.05). The protein and mRNA levels of E⁃Cadherin in oe⁃HIF⁃1α+E

2

group were higher than those in oe⁃HIF⁃1α and oe⁃vector group

but the levels in oe⁃HIF⁃1α group were lower than those in the oe⁃vector group (

P

<

0.05). The protein and mRNA levels of Vimentin in oe⁃HIF⁃1α+E

2

group were lower than oe⁃HIF⁃1α and oe⁃vector group

but the levels inVimentin in oe⁃HIF⁃1α group were higher than in oe⁃vector group (

P

<

0.05).

Conclusion

2

E

2

may be inhibited by HIF⁃1α to promote the EMT process in ESCs

thereby promoting the invasion and metastasis of ectopic endometrium

HIF⁃1α is expected to become one of the targets for the treatment of endometriosis.

关键词

Keywords

references

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HEINEMANN K , IMTHURN B , MARIONS L , et al . Safety of dienogest and other hormonal treatments for endometriosis in real⁃world clinical practice (VIPOS): A large noninterventional study [J ] . Adv Ther , 2020 , 37 ( 5 ): 2528 ⁃ 2537 .

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AGOSTINIS C , BALDUIT A , MANGOGNA A , et al . Immunological basis of the endometriosis: The complement system as a potential therapeutic target [J ] . Front Immunol , 2021 , 11 : 599117 .

OSUGA Y , SEKI Y , TANIMOTO M , et al . Relugolix, an oral gonadotropin⁃releasing hormone (GnRH) receptor antagonist, in women with endometriosis⁃associated pain: Phase 2 safety and efficacy 24⁃week results [J ] . BMC Womens Health , 2021 , 21 ( 1 ): 250 .

SIMOPOULOU M , RAPANI A , GRIGORIADIS S , et al . Getting to know endometriosis⁃related infertility better: A review on how endometriosis affects oocyte quality and embryo development [J ] . Biomedicines , 2021 , 9 ( 3 ): 273 .

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GODWIN T D , THOMAS KELLY S , BREW T P , et al . E⁃cadherin⁃deficient cells have synthetic lethal vulnerabilities in plasma membrane organisation, dynamics and function [J ] . Gastric Cancer , 2019 , 22 ( 2 ): 273 ⁃ 286 .

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