Downregulated ETV4 inhibits the proliferation, migration, and invasion of trophoblast cells in preeclampsia

in Reproduction
Authors:
Qiuling JieHainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China
Department of Reproductive Medicine, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China
Hainan Provincial Clinical Research Center for Thalassemia, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China
Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou, China
Haikou Key Laboratory for Preservation of Human Genetic Resource, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China

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Lijun ChenHainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China
Department of Reproductive Medicine, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China
Hainan Provincial Clinical Research Center for Thalassemia, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China
Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou, China
Haikou Key Laboratory for Preservation of Human Genetic Resource, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China

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Jiangying LiangHainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China
Department of Reproductive Medicine, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China
Hainan Provincial Clinical Research Center for Thalassemia, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China
Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou, China
Haikou Key Laboratory for Preservation of Human Genetic Resource, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China

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Xiaohui YangHainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China
Department of Reproductive Medicine, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China
Hainan Provincial Clinical Research Center for Thalassemia, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China
Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou, China
Haikou Key Laboratory for Preservation of Human Genetic Resource, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China

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Fei SunHainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China
Department of Reproductive Medicine, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China
Hainan Provincial Clinical Research Center for Thalassemia, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China
Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou, China
Haikou Key Laboratory for Preservation of Human Genetic Resource, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China
Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China

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Yanlin MaHainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China
Department of Reproductive Medicine, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China
Hainan Provincial Clinical Research Center for Thalassemia, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China
Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou, China
Haikou Key Laboratory for Preservation of Human Genetic Resource, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China

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Correspondence should be addressed to Y Ma; Email: mayl1990@foxmail.com

*(Q Jie and L Chen contributed equally to this work)

DOI:
https://doi.org/10.1530/REP-22-0184
Volume/Issue:
Volume 165: Issue 4
Page Range:
373–381
Article Type:
Research Article
Online Publication Date:
08 Mar 2023
Copyright:
© Society for Reproduction and Fertility 2023
Restricted access

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In brief

Preeclampsia is a pregnancy complication that can lead to severe adverse maternal and fetal outcomes, but the mechanisms underlying the development of preeclampsia are not fully understood. This study shows that ETV4 plays an essential role in the proliferation, invasion, and migration of trophoblast cells by regulating MMP-2 and MMP-9 and is involved in the pathogenesis of preeclampsia.

Abstract

Preeclampsia (PE) is a pregnancy complication that can lead to severe adverse maternal and fetal outcomes. However, the mechanisms underlying the development of PE are not fully understood. ETS Variant Transcription Factor 4 (ETV4) plays an important role in cell proliferation, migration, and invasion. In this study, we aimed to explore the potential function of ETV4 in placental trophoblast cells. We analyzed the expression and location of ETV4 in PE and uncomplicated placental tissues using RT-qPCR, Western blotting, immunohistochemistry, and immunofluorescence staining. The results showed that both the mRNA and protein levels of ETV4 were markedly decreased in PE placental tissues compared with placental tissues from women with uncomplicated pregnancies (P < 0.05). Then, the effects of ETV4 on HTR-8/SVneo and Bewo cell proliferation, migration, and invasion were evaluated by MTT, 5-ethynyl-2-deoxyuridine (EdU), wound healing, and Transwell assays, respectively. The results showed that ETV4 knockdown inhibited both HTR-8/SVneo and Bewo cell proliferation, migration, and invasion (P < 0.05). Conversely, overexpression of ETV4 promoted both HTR-8/SVneo and Bewo cell proliferation, migration, and invasion (P < 0.05). We then measured the expression of MMP-2 and MMP-9 in HTR8/SVneo cells. We found that ETV4 knockdown decreased the mRNA and protein expression of MMP-2 and MMP-9, while ETV4 overexpression increased MMP-2 and MMP-9 mRNA and protein expression (P < 0.05). In conclusion, ETV4 plays an essential role in the proliferation, invasion, and migration of trophoblast cells by regulating MMP-2 and MMP-9. Our findings provide novel insight into the mechanisms underlying the occurrence of PE.

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Print ISSN:
1470-1626
Online ISSN:
1741-7899

     An official journal of

    Society for Reproduction and Fertility

 

Copyright:
© Society for Reproduction and Fertility 2023
Page(s):
9
Received Date:
03 Jun 2022
Accepted Date:
30 Jan 2023
Print Publication Date:
01 Apr 2023
Online Publication Date:
08 Mar 2023

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