TCF3 regulates human endometrial stromal cell proliferation and migration in RPL

in Reproduction
Authors:
Xiao-Wei Wei The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
Shanghai Municipal Key Clinical Specialty, Shanghai, China
Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

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https://orcid.org/0000-0001-8090-2431
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Xue-Qing Liu The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
Shanghai Municipal Key Clinical Specialty, Shanghai, China
Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

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Yu-Chen Zhang Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University of Medicine, Shanghai, China

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https://orcid.org/0000-0002-8505-6278
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Chuan-Mei Qin The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
Shanghai Municipal Key Clinical Specialty, Shanghai, China
Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

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Yi Lin The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
Shanghai Municipal Key Clinical Specialty, Shanghai, China
Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

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, and
Fu-Ju Tian The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
Shanghai Municipal Key Clinical Specialty, Shanghai, China
Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

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Correspondence should be addressed to F-J Tian; Email: fjtian@sibs.ac.cn

*(X-W Wei and X-Q Liu contributed equally to this work)

DOI:
https://doi.org/10.1530/REP-21-0463
Volume/Issue:
Volume 163: Issue 5
Page Range:
281–291
Article Type:
Research Article
Online Publication Date:
29 Mar 2022
Copyright:
© Society for Reproduction and Fertility 2022
Restricted access
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Recurrent pregnancy loss (RPL) is a multifactorial condition with no explanation of miscarriage in approximately half of the RPL patients, consequently leaving deep physical and emotional sequels. Transcription factor 3 (TCF3 or E2A), is a unique member of the LEF/TCF family and plays an important role in embryogenesis. However, its function in RPL is poorly understood. Using real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry, we demonstrated that TCF3 was downregulated in decidual tissues from RPL patients compared with healthy control (HC). Further, TCF3 knockdown inhibited proliferation, induced G0/G1 phase arrest, and promoted migration in human endometrial stromal cells (HESCs), while overexpression of TCF3 exhibited the opposite effects. RNA-sequencing analysis combined with gene-set enrichment analysis results showed that the mitogen-activated protein kinase pathway is potentially downstream of TCF3. Knockdown of TCF3 confirmed increased p38 phosphorylation, while overexpression of TCF3 inhibited p38 phosphorylation. Furthermore, we found that TCF3 protein level was decreased in HESCs under hypoxic incubation, while hypoxia-inducible factor-1α (HIF1A) knockdown increased the expression of TCF3. TCF3 overexpression recovered the proliferation ability of HESCs inhibited by hypoxia and reversed hypoxia-induced migration. Consistently, we found that RPL patients had a significantly higher level of HIF1A in the decidual tissue than HC. Overall, this study clarifies that increased HIF1A in the decidua contributes to the occurrence of RPL through the TCF3/p38 signaling pathway.

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

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