SOX4 facilitates PGR protein stability and FOXO1 expression conducive for human endometrial decidualization
- The First Affiliated Hospital of Guangxi Medical University, China
- Xiamen University, China
- Liuzhou Maternity and Child Health Hospital, China
- 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).
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Gene expression in human endometrium cells (ATCC 4003) after Sox4 was abolished by siRNANCBI Gene Expression Omnibus, GSE146280.
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Gene expression in human endometrium cells (ATCC 4003) after Sox4 was abolished by siRNANCBI Gene Expression Omnibus, GSE174602.
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Gene expression in human endometrium cells (ATCC 4003) after Sox4 was abolished by siRNANCBI Gene Expression Omnibus, GSE174602.
Article and author information
Author details
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
- T Rajendra Kumar, University of Colorado, United States
Version history
- Received: July 9, 2021
- Preprint posted: July 19, 2021 (view preprint)
- Accepted: March 3, 2022
- Accepted Manuscript published: March 4, 2022 (version 1)
- 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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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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