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Role of ARID1A in the Regulation of Human Trophoblast Migration and Invasion

  • Reproductive Biology: Original Article
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Abstract

Migration and invasion of trophoblasts is critical for human placental development, trophoblastic differentiation, and pregnancy-associated diseases. AT-rich interactive domain-containing protein 1A (ARID1A), a subunit of the SWI-SNF complex, has been suggested to participate in the regulation of fertility via placental disruption in mice. However, whether ARID1A regulates human placental development and function remains unknown. Here, using human trophoblast-like JEG-3 cell line, we report that ARID1A controls trophoblast cell migration and invasion. Overexpression of ARID1A inhibits JEG-3 cell migration and invasion, whereas knockdown of ARID1A promotes migration and invasion in JEG-3 cells. Mechanistically, while ARID1A reduces JEG-3 cell migration by down-regulation of Snail transcription, it restrains JEG-3 cell invasion by binding to and destabilization of MMP-9 protein. Finally, ARID1A is apparently up-regulated in placental tissues of preeclampsia compared to that of normal pregnancies. Our results thereby imply that ARID1A acts as a critical gene in supporting the physiological function of human mature placenta.

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Abbreviations

ARID1A:

AT-rich interactive domain-containing protein 1A

CHX:

Cycloheximide

CTB:

Cytotrophoblast

DAB:

Diaminobenzidine

DAPI:

4′,6-Diamidino-2-phenylindole

EMT:

Epithelial-mesenchymal transition

EVT:

Extravillous trophoblast

HET293T:

Human embryonic kidney 293T

MMP:

Matrix metalloproteinase

PE:

Preeclampsia

PLA:

Proximity ligation assay

STB:

Syncytiotrophoblast

ZEB:

Zinc-finger E-box-binding

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Availability of Data and Material

All data generated or analyzed during this study are included in this published article.

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Funding

This work is supported by the Medical and Health Science and Technology Project of Zhejiang Province (No. 2020KY504) to M. Jin and by the Starting Research Fund from the Children’s Hospital, Zhejiang University School of Medicine (No. 481) and National Natural Science Foundation of China (No. 31801207) to C. Tang.

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Author notes

  1. Meiyuan Jin and Shouying Xu contributed equally to this work.

Authors and Affiliations

  1. Department of Obstetrics, Tongde Hospital of Zhejiang Province, Hangzhou, 310012, China

    Meiyuan Jin

  2. National Clinical Research Center for Child Health of the Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China

    Shouying Xu & Chao Tang

  3. Department of Ophthalmology, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, China

    Jiayong Li

  4. College of Pharmaceutical Science, Zhejiang University, Hangzhou, 310058, China

    Lu Li

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  1. Meiyuan Jin
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  4. Lu Li
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  5. Chao Tang
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Contributions

M. Jin and S. Xu performed the research and analyzed the data. J. Li and L. Li edited the manuscript. C. Tang designed the experiments and wrote the manuscript.

Corresponding author

Correspondence to Chao Tang.

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The Ethics Committee of Tongde Hospital of Zhejiang Province approved all the protocols of the study.

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All participants provided written informed consent for the use of placental villus tissues.

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Jin, M., Xu, S., Li, J. et al. Role of ARID1A in the Regulation of Human Trophoblast Migration and Invasion. Reprod. Sci. 29, 2363–2373 (2022). https://doi.org/10.1007/s43032-021-00686-0

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