SOX4 facilitates PGR protein stability and FOXO1 expression conducive for human endometrial decidualization

  1. Pinxiu Huang
  2. Wenbo Deng
  3. Haili Bao
  4. Zhong Lin
  5. Mengying Liu
  6. Jinxiang Wu
  7. Xiaobo Zhou
  8. Manting Qiao
  9. Yihua Yang
  10. Han Cai
  11. Faiza Rao
  12. Jingsi Chen
  13. Dunjin Chen
  14. Jinhua Lu
  15. Haibin Wang  Is a corresponding author
  16. Aiping Qin  Is a corresponding author
  17. Shuangbo Kong  Is a corresponding author
  1. The First Affiliated Hospital of Guangxi Medical University, China
  2. Xiamen University, China
  3. Liuzhou Maternity and Child Health Hospital, China
  4. The Third Affiliated Hospital of Guangzhou Medical University, China

Abstract

The establishment of pregnancy in human necessitates appropriate decidualization of stromal cells, which involves steroids regulated periodic transformation of endometrial stromal cells during menstrual cycle. However, the potential molecular regulatory mechanism underlying the initiation and maintenance of decidualization in humans is yet to be fully elucidated. In this investigation, we document that SOX4 is a key regulator of human endometrial stromal cells (HESCs) decidualization by directly regulating FOXO1 expression as revealed by whole genomic binding of SOX4 assay and RNA-Seq. Besides, our immunoprecipitation and mass spectrometry results unravel that SOX4 modulates progesterone receptor (PGR) stability through repressing E3 ubiquitin ligase HERC4 mediated degradation. More importantly, we provide evidence that dysregulated SOX4-HERC4-PGR axis is a potential cause of defective decidualization and recurrent implantation failure (RIF) in IVF patients. In summary, this study evidences that SOX4 is a new and critical regulator for human endometrial decidualization, and provides insightful information for the pathology of decidualization-related infertility and will pave the way for pregnancy improvement.

Data availability

The sequencing data generated in this study have been deposited in the Gene Expression Omnibus database under accession code GSE146280 (RNA-Seq), GSE174602 (ChIP-Seq in stromal cell line) and GSE174602 (ChIP-Seq in primary cultured stromal cell).

The following data sets were generated

Article and author information

Author details

  1. Pinxiu Huang

    Department of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Wenbo Deng

    Department of Obstetrics and Gynecology, Xiamen University, Xiamen, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Haili Bao

    Department of Obstetrics and Gynecology, Xiamen University, Xiamen, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Zhong Lin

    Department of Reproductive Medicine, Liuzhou Maternity and Child Health Hospital, Liuzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Mengying Liu

    Department of Obstetrics and Gynecology, Xiamen University, Xiamen, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5987-1287
  6. Jinxiang Wu

    Department of Obstetrics and Gynecology, Xiamen University, Xiamen, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Xiaobo Zhou

    Department of Obstetrics and Gynecology, Xiamen University, Xiamen, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Manting Qiao

    Department of Obstetrics and Gynecology, Xiamen University, Xiamen, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Yihua Yang

    Department of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Han Cai

    Department of Obstetrics and Gynecology, Xiamen University, Xiamen, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Faiza Rao

    Department of Obstetrics and Gynecology, Xiamen University, Xiamen, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Jingsi Chen

    Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  13. Dunjin Chen

    Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  14. Jinhua Lu

    Department of Obstetrics and Gynecology, Xiamen University, Xiamen, China
    Competing interests
    The authors declare that no competing interests exist.
  15. Haibin Wang

    Department of Obstetrics and Gynecology, Xiamen University, Xiamen, China
    For correspondence
    haibin.wang@vip.163.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9865-324X
  16. Aiping Qin

    Department of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
    For correspondence
    qinaiping@gxmu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
  17. Shuangbo Kong

    Department of Obstetrics and Gynecology, Xiamen University, Xiamen, China
    For correspondence
    shuangbo_kong@163.com
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Key R&D program of China (2021YFC2700302)

  • Haibin Wang

Guangxi natural science foundation project (2019JJB140179)

  • Pinxiu Huang

National Key R&D program of China (2018YFC1004404)

  • Shuangbo Kong

National Natural Science Foundation of China (81830045)

  • Haibin Wang

National Natural Science Foundation of China (82030040)

  • Haibin Wang

National Natural Science Foundation of China (81960280)

  • Aiping Qin

National Natural Science Foundation of China (82001553)

  • Pinxiu Huang

National Natural Science Foundation of China (81701483)

  • Wenbo Deng

National Natural Science Foundation of China (81971419)

  • Wenbo Deng

Fundamental Research Funds of the Central Universities (20720190073)

  • Wenbo Deng

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The studies for collecting the endometrial tissue was approved by The Ethical Committee of the Faculty of the Liuzhou Maternity and Child Health Hospital (2020-074). The studies for isolating the primary endometrial cells was approved by The Ethical Committee of The First Affiliated Hospital of Xiamen University (XMYY-2021KYSB044). All participants signed informed consent.

Reviewing Editor

  1. T Rajendra Kumar, University of Colorado, United States

Version history

  1. Received: July 9, 2021
  2. Preprint posted: July 19, 2021 (view preprint)
  3. Accepted: March 3, 2022
  4. Accepted Manuscript published: March 4, 2022 (version 1)
  5. Version of Record published: March 15, 2022 (version 2)

Copyright

© 2022, Huang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Pinxiu Huang
  2. Wenbo Deng
  3. Haili Bao
  4. Zhong Lin
  5. Mengying Liu
  6. Jinxiang Wu
  7. Xiaobo Zhou
  8. Manting Qiao
  9. Yihua Yang
  10. Han Cai
  11. Faiza Rao
  12. Jingsi Chen
  13. Dunjin Chen
  14. Jinhua Lu
  15. Haibin Wang
  16. Aiping Qin
  17. Shuangbo Kong
(2022)
SOX4 facilitates PGR protein stability and FOXO1 expression conducive for human endometrial decidualization
eLife 11:e72073.
https://doi.org/10.7554/eLife.72073

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