MAX deficiency impairs human endometrial decidualization through down-regulating OSR2 in women with recurrent spontaneous abortion
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Published:2022-02-11
Issue:2
Volume:388
Page:453-469
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ISSN:0302-766X
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Container-title:Cell and Tissue Research
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language:en
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Short-container-title:Cell Tissue Res
Author:
Ma Weixu, Cao Mingzhu, Bi Shilei, Du Lili, Chen Jingsi, Wang Haibin, Jiang Yufei, Wu Yixuan, Liao Yixin, Kong Shuangbo, Liu JianqiaoORCID
Abstract
AbstractHuman uterine stromal cell undergoes decidualization for pregnancy establishment and maintenance, which involved extensive proliferation and differentiation. Increasing studies have suggested that recurrent spontaneous abortion (RSA) may result from defective endometrial stromal decidualization. However, the critical molecular mechanisms underlying impaired decidualization during RSA are still elusive. By using our recently published single-cell RNA sequencing (scRNA-seq) atlas, we found that MYC-associated factor X (MAX) was significantly downregulated in the stromal cells derived from decidual tissues of women with RSA, followed by verification with immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR). MAX knockdown significantly impairs human endometrial stromal cells (HESCs) proliferation as determined by MTS assay and Ki67 immunostaining, and decidualization determined by F-actin, and decidualization markers. RNA-seq together with chromatin immunoprecipitation sequencing (ChIP-seq) and cleavage under targets and release using nuclease sequencing (CUT&RUN-seq) analysis were applied to explore the molecular mechanisms of MAX in regulation of decidualization, followed by dual-luciferase reporter assay to verify that MAX targets to (odd-skipped related transcription factor 2) OSR2 directly. Reduced expression of OSR2 was also confirmed in decidual tissues in women with RSA by IHC and qRT-PCR. OSR2 knockdown also significantly impairs HESCs decidualization. OSR2-overexpression could at least partly rescue the downregulated insulin-like growth factor binding protein 1 (IGFBP1) expression level in response to MAX knockdown. Collectively, MAX deficiency observed in RSA stromal cells not only attenuates HESCs proliferation but also impairs HESCs decidualization by downregulating OSR2 expression at transcriptional level directly.
Funder
the National Key R&D Program of China the National Natural Science Foundation of China the Medical Key Discipline of Guangzhou General Program of Guangdong Province Natural Science Foundation
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Histology,Pathology and Forensic Medicine
Reference54 articles.
1. Ali S, Majid S, Niamat AM, Taing S, El-Serehy HA, Al-Misned FA (2020) Evaluation of etiology and pregnancy outcome in recurrent miscarriage patients. Saudi J Biol Sci 27:2809–2817 2. Augert A, Mathsyaraja H, Ibrahim AH, Freie B, Geuenich MJ, Cheng PF, Alibeckoff SP, Wu N, Hiatt JB, Basom R, Gazdar A, Sullivan LB, Eisenman RN, MacPherson D (2020) MAX functions as a tumor suppressor and rewires metabolism in small cell lung cancer. Cancer Cell 38:97–114 3. Ayer DE, Eisenman RN (1993) A switch from Myc: Max to Mad: Max heterocomplexes accompanies monocyte/ macrophage differentiation. Genes Dev 7:2110–2119 4. Bender AR, Christiansen OB, Elson J, Kolte AM, Lewis S, Middeldorp S, Nelen W, Peramo B, Quenby S, Vermeulen N, Goddijn M (2018) ESHRE guideline: recurrent pregnancy loss. Hum Reprod Open 2018:hoy004 5. Brighton PJ, Maruyama Y, Fishwick K, Vrljicak P, Tewary S, Fujihara R, Muter J, Lucas ES, Yamada T, Woods L, Lucciola R, Lee YH, Takeda S, Ott S, Hemberger M, Quenby S, Brosens JJ (2017) Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium. Elife 6:e31274
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