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ATF3 deficiency impairs the proliferative–secretory phase transition and decidualization in RIF patients

Decidualization is a complex process involving cellular proliferation and differentiation of the endometrial stroma and is required to establish and support pregnancy. Dysregulated decidualization has been reported to be a critical cause of recurrent implantation failure (RIF). In this study, we fou...

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Autores principales: Wang, Zhilong, Liu, Yang, Liu, Jingyu, Kong, Na, Jiang, Yue, Jiang, Ruiwei, Zhen, Xin, Zhou, Jidong, Li, Chaojun, Sun, Haixiang, Yan, Guijun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041902/
https://www.ncbi.nlm.nih.gov/pubmed/33846304
http://dx.doi.org/10.1038/s41419-021-03679-8
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author Wang, Zhilong
Liu, Yang
Liu, Jingyu
Kong, Na
Jiang, Yue
Jiang, Ruiwei
Zhen, Xin
Zhou, Jidong
Li, Chaojun
Sun, Haixiang
Yan, Guijun
author_facet Wang, Zhilong
Liu, Yang
Liu, Jingyu
Kong, Na
Jiang, Yue
Jiang, Ruiwei
Zhen, Xin
Zhou, Jidong
Li, Chaojun
Sun, Haixiang
Yan, Guijun
author_sort Wang, Zhilong
collection PubMed
description Decidualization is a complex process involving cellular proliferation and differentiation of the endometrial stroma and is required to establish and support pregnancy. Dysregulated decidualization has been reported to be a critical cause of recurrent implantation failure (RIF). In this study, we found that Activating transcription factor 3 (ATF3) expression was significantly downregulated in the endometrium of RIF patients. Knockdown of ATF3 in human endometrium stromal cells (hESCs) hampers decidualization, while overexpression could trigger the expression of decidual marker genes, and ameliorate the decidualization of hESCs from RIF patients. Mechanistically, ATF3 promotes decidualization by upregulating FOXO1 via suppressing miR-135b expression. In addition, the endometrium of RIF patients was hyperproliferative, while overexpression of ATF3 inhibited the proliferation of hESCs through CDKN1A. These data demonstrate the critical roles of endometrial ATF3 in regulating decidualization and proliferation, and dysregulation of ATF3 in the endometrium may be a novel cause of RIF and therefore represent a potential therapeutic target for RIF.
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spelling pubmed-80419022021-04-28 ATF3 deficiency impairs the proliferative–secretory phase transition and decidualization in RIF patients Wang, Zhilong Liu, Yang Liu, Jingyu Kong, Na Jiang, Yue Jiang, Ruiwei Zhen, Xin Zhou, Jidong Li, Chaojun Sun, Haixiang Yan, Guijun Cell Death Dis Article Decidualization is a complex process involving cellular proliferation and differentiation of the endometrial stroma and is required to establish and support pregnancy. Dysregulated decidualization has been reported to be a critical cause of recurrent implantation failure (RIF). In this study, we found that Activating transcription factor 3 (ATF3) expression was significantly downregulated in the endometrium of RIF patients. Knockdown of ATF3 in human endometrium stromal cells (hESCs) hampers decidualization, while overexpression could trigger the expression of decidual marker genes, and ameliorate the decidualization of hESCs from RIF patients. Mechanistically, ATF3 promotes decidualization by upregulating FOXO1 via suppressing miR-135b expression. In addition, the endometrium of RIF patients was hyperproliferative, while overexpression of ATF3 inhibited the proliferation of hESCs through CDKN1A. These data demonstrate the critical roles of endometrial ATF3 in regulating decidualization and proliferation, and dysregulation of ATF3 in the endometrium may be a novel cause of RIF and therefore represent a potential therapeutic target for RIF. Nature Publishing Group UK 2021-04-12 /pmc/articles/PMC8041902/ /pubmed/33846304 http://dx.doi.org/10.1038/s41419-021-03679-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wang, Zhilong
Liu, Yang
Liu, Jingyu
Kong, Na
Jiang, Yue
Jiang, Ruiwei
Zhen, Xin
Zhou, Jidong
Li, Chaojun
Sun, Haixiang
Yan, Guijun
ATF3 deficiency impairs the proliferative–secretory phase transition and decidualization in RIF patients
title ATF3 deficiency impairs the proliferative–secretory phase transition and decidualization in RIF patients
title_full ATF3 deficiency impairs the proliferative–secretory phase transition and decidualization in RIF patients
title_fullStr ATF3 deficiency impairs the proliferative–secretory phase transition and decidualization in RIF patients
title_full_unstemmed ATF3 deficiency impairs the proliferative–secretory phase transition and decidualization in RIF patients
title_short ATF3 deficiency impairs the proliferative–secretory phase transition and decidualization in RIF patients
title_sort atf3 deficiency impairs the proliferative–secretory phase transition and decidualization in rif patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041902/
https://www.ncbi.nlm.nih.gov/pubmed/33846304
http://dx.doi.org/10.1038/s41419-021-03679-8
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