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

Pinxiu Huang; Wenbo Deng; Haili Bao; Zhong Lin; Mengying Liu; Jinxiang Wu; Xiaobo Zhou; Manting Qiao; Yihua Yang; Han Cai; Faiza Rao; Jingsi Chen; Dunjin Chen; Jinhua Lu; Haibin Wang; Aiping Qin; Shuangbo Kong

doi:10.7554/eLife.72073

eLife (Mar 2022)

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

Pinxiu Huang,
Wenbo Deng,
Haili Bao,
Zhong Lin,
Mengying Liu,
Jinxiang Wu,
Xiaobo Zhou,
Manting Qiao,
Yihua Yang,
Han Cai,
Faiza Rao,
Jingsi Chen,
Dunjin Chen,
Jinhua Lu,
Haibin Wang,
Aiping Qin,
Shuangbo Kong

Affiliations

Pinxiu Huang: Department of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China; Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; Department of Reproductive Medicine, Liuzhou Maternity and Child Health Hospital, Liuzhou, China; Affiliated Maternity Hospital and Affiliated Children’s Hospital of Guangxi University of Science and Technology, Liuzhou, China
Wenbo Deng: Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
Haili Bao: Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
Zhong Lin: Department of Reproductive Medicine, Liuzhou Maternity and Child Health Hospital, Liuzhou, China
Mengying Liu: ORCiD; Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
Jinxiang Wu: Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
Xiaobo Zhou: Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
Manting Qiao: Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
Yihua Yang: Department of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
Han Cai: Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
Faiza Rao: Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
Jingsi Chen: Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Dunjin Chen: Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Jinhua Lu: Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
Haibin Wang: ORCiD; Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
Aiping Qin: Department of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
Shuangbo Kong: ORCiD; Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China

DOI: https://doi.org/10.7554/eLife.72073
Journal volume & issue: Vol. 11

Abstract

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The establishment of pregnancy in human necessitates appropriate decidualization of stromal cells, which involves steroids regulated periodic transformation of endometrial stromal cells during the 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 decidualization by directly regulating FOXO1 expression as revealed by whole genomic binding of SOX4 assay and RNA sequencing. 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 in in-vitro fertilization (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.

Published in eLife

ISSN: 2050-084X (Online)
Publisher: eLife Sciences Publications Ltd
Country of publisher: United Kingdom
LCC subjects: Medicine; Science: Biology (General)
Website: https://elifesciences.org

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