Hypoxia/reoxygenation attenuates migration and invasion of human extracellular villus trophoblast cells <italic style="font-style: italic">via</italic> DNA methyltransferase pathway

Sichen HU; Xi LAN; Yubin DING; Fangfang LI; Enxiang CHEN; Lijuan FU

doi:10.16016/j.2097-0927.202304072

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Hypoxia/reoxygenation attenuates migration and invasion of human extracellular villus trophoblast cells via DNA methyltransferase pathway

Basic Medicine | 更新时间：2026-01-09

- Hypoxia/reoxygenation attenuates migration and invasion of human extracellular villus trophoblast cells via DNA methyltransferase pathway
- Journal of Army Medical University Vol. 45, Issue 19, Pages: 2057-2064(2023)
- 作者机构：
  
  1.401331 重庆，重庆医科大学：公共卫生学院
  2.400016 重庆，生殖生物学实验室，教育部生殖与发育国际合作联合实验室
  3.400016 重庆，重庆医科大学基础医学院
  4.410219 长沙，长沙医学院基础医学院
  5.401331 重庆，重庆医科大学：中医药学院
- 作者简介：
- 基金信息：
  
  the Natural Science Foundation of Chongqing(cstc2021jcyj-msxmX0236)
- DOI：10.16016/j.2097-0927.202304072
  CLC： R321.4;R363.21;R364.4
- Received：17 April 2023，
  
  Revised：2023-05-12，
  
  Published：15 October 2023
- 稿件说明：
移动端阅览
Sichen HU, Xi LAN, Yubin DING, et al. Hypoxia/reoxygenation attenuates migration and invasion of human extracellular villus trophoblast cells via DNA methyltransferase pathway[J]. Journal of Army Medical University, 2023, 45(19): 2057-2064.
DOI：

Sichen HU, Xi LAN, Yubin DING, et al. Hypoxia/reoxygenation attenuates migration and invasion of human extracellular villus trophoblast cells via DNA methyltransferase pathway[J]. Journal of Army Medical University, 2023, 45(19): 2057-2064. DOI： 10.16016/j.2097-0927.202304072.

摘要

目的

探讨缺氧/复氧(hypoxia/reoxygenation，H/R)对人绒毛外滋养细胞(extravillous trophoblast，EVT)侵袭能力的调控机制。

方法

体外培养EVT永生化细胞系HTR-8/SVneo、早孕胎盘绒毛分离的原代EVT细胞和绒毛外植体，1% O

和20% O

浓度转换条件下模拟EVT细胞侵入子宫时的H/R环境，Western blot、免疫荧光技术检测细胞侵袭等关键因子的表达，Transwell小室法检测细胞迁移和侵袭。

结果

经H/R诱导后，HTR-8/SVneo细胞迁移和侵袭能力减弱，体外培养的绒毛外植体的外延能力和分离的原代EVT细胞迁移、侵袭能力均减弱；H/R条件下，HTR-8/SVneo细胞中基质金属蛋白酶MMP-2和MMP-9，整合素integrin-β1和integrin-α5蛋白水平降低(

＜0.05)，DNA甲基转移酶(DNA methyltransferase

DNMTs)的蛋白表达亦下调(

＜0.01)；H/R条件下，原代EVT细胞中上皮-间充质转化(epithelial-mesenchymal transition，EMT)的正调控因子Slug、Snails等被抑制(

＜0.05)，上皮细胞标志因子E-cadherin表达上升(

＜0.01)，MMP-2和-9、integrin-β1和-α5蛋白水平下降(

＜0.05)，细胞侵袭能力下降并伴随DNMT1、DNMT3A的表达下降(

＜0.05)。HTR-8/SVneo细胞中过表达DNMT1、DNMT3A和DNMT3B可促进间质型标志因子N-cadherin、MMP-2和-9的蛋白表达上调(

＜0.05)。

结论

H/R通过DNMTs调控MMP-2/9等EMT相关因子的表达从而减弱EVT细胞迁移和侵袭能力。

Abstract

Objective

To explore the regulative mechanism of hypoxia/reoxygen (H/R) for invasion ability of extravillous trophoblast (EVT).

Methods

Immortalized human EVT cell line HTR-8/SVneo in early pregnancy

primary EVT cells isolated from the villi of placenta in early pregnancy

and villi explants were cultured re

spectively. A simulation model of H/R environment in EVT cells invading the uterus was established under the conversion conditions of 1% O

for 24 h to 20% O

for another 24 h. Western blotting and immunofluorescence assay were used to detect the expression of key factors such as cell invasion

and Transwell chamber test was employed to observe cell migration and invasion.

Results

After H/R induction

the migration and invasion abilities of HTR-8/SVneo cells were weakened

and the epitaxial ability of cultured villi explants and the migration and invasion abilities of isolated primary EVT cells were also weakened. Under H/R conditions

the expression levels of MMP-2 and MMP-9

integrin-β1 and integrin-α5 were decreased in HTR-8/SVneo cells (

0.05)

and the protein expression of DNA methyltransferase (DNMTs) was also down-regulated (

0.01). In the primary EVT cells under H/R condition

the expression levels of epithelial-mesenchymal transition (EMT) positive regulatory factors

Slug and Snails

were inhibited (

0.05)

that of epithelial cell marker E-cadherin was increased (

0.01)

protein levels of MMP-2 and MMP-9

integrin-β1 and integrin-α5 were decreased (

0.05)

and cell invasion ability was reduced along with decreased DNMT1 and DNMT3A expression (

0.05). However

overexpression of DNMT1

DNMT3A and DNMT3B in HTR-8/SVneo cells promoted the up-regulation of interstitial markers N-cadherin

and MMP-2 and MMP-9 (

0.05).

Conclusion

H/R regulates the expression of EMT-related factors such as MMP-2/-9 through DNMTs

and thereby reduces the migration and invasion abilities of EVT cells.

关键词

Keywords

references

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⁰

Hypoxia/reoxygenation attenuates migration and invasion of human extracellular villus trophoblast cells via DNA methyltransferase pathway

DOI：10.16016/j.2097-0927.202304072

摘要

Abstract

关键词

Keywords

references