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
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
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
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
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.
