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Microgravity inhibits decidualization via decreasing Akt activity and FOXO3a expression in human endometrial stromal cells

Decidualization is characterized by the differentiation of endometrial stromal cells (eSCs), which is critical for embryo implantation and maintenance of pregnancy. In the present study, we investigated the possible effect of simulated microgravity (SM) on the process of proliferation and in vitro d...

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Autores principales: Cho, Hye-Jeong, Baek, Mi-Ock, Khaliq, Sana Abdul, Chon, Seung Joo, Son, Kuk Hui, Lee, Sung Ho, Yoon, Mee-Sup
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702225/
https://www.ncbi.nlm.nih.gov/pubmed/31431660
http://dx.doi.org/10.1038/s41598-019-48580-9
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author Cho, Hye-Jeong
Baek, Mi-Ock
Khaliq, Sana Abdul
Chon, Seung Joo
Son, Kuk Hui
Lee, Sung Ho
Yoon, Mee-Sup
author_facet Cho, Hye-Jeong
Baek, Mi-Ock
Khaliq, Sana Abdul
Chon, Seung Joo
Son, Kuk Hui
Lee, Sung Ho
Yoon, Mee-Sup
author_sort Cho, Hye-Jeong
collection PubMed
description Decidualization is characterized by the differentiation of endometrial stromal cells (eSCs), which is critical for embryo implantation and maintenance of pregnancy. In the present study, we investigated the possible effect of simulated microgravity (SM) on the process of proliferation and in vitro decidualization using primary human eSCs. Exposure to SM for 36 h decreased the proliferation and migration of eSCs significantly, without inducing cell death and changes in cell cycle progression. The phosphorylation of Akt decreased under SM conditions in human eSCs, accompanied by a simultaneous decrease in the level of matrix metalloproteinase (MMP)-2 and FOXO3a. Treatment with Akti, an Akt inhibitor, decreased MMP-2 expression, but not FOXO3a expression. The decreased level of FOXO3a under SM conditions impeded autophagic flux by reducing the levels of autophagy-related genes. In addition, pre-exposure of eSCs to SM significantly inhibited 8-Br-cAMP induced decidualization, whereas restoration of the growth status under SM conditions by removing 8-Br-cAMP remained unchanged. Treatment of human eSCs with SC-79, an Akt activator, restored the reduced migration of eSCs and decidualization under SM conditions. In conclusion, exposure to SM inhibited decidualization in eSCs by decreasing proliferation and migration through Akt/MMP and FOXO3a/autophagic flux.
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spelling pubmed-67022252019-08-23 Microgravity inhibits decidualization via decreasing Akt activity and FOXO3a expression in human endometrial stromal cells Cho, Hye-Jeong Baek, Mi-Ock Khaliq, Sana Abdul Chon, Seung Joo Son, Kuk Hui Lee, Sung Ho Yoon, Mee-Sup Sci Rep Article Decidualization is characterized by the differentiation of endometrial stromal cells (eSCs), which is critical for embryo implantation and maintenance of pregnancy. In the present study, we investigated the possible effect of simulated microgravity (SM) on the process of proliferation and in vitro decidualization using primary human eSCs. Exposure to SM for 36 h decreased the proliferation and migration of eSCs significantly, without inducing cell death and changes in cell cycle progression. The phosphorylation of Akt decreased under SM conditions in human eSCs, accompanied by a simultaneous decrease in the level of matrix metalloproteinase (MMP)-2 and FOXO3a. Treatment with Akti, an Akt inhibitor, decreased MMP-2 expression, but not FOXO3a expression. The decreased level of FOXO3a under SM conditions impeded autophagic flux by reducing the levels of autophagy-related genes. In addition, pre-exposure of eSCs to SM significantly inhibited 8-Br-cAMP induced decidualization, whereas restoration of the growth status under SM conditions by removing 8-Br-cAMP remained unchanged. Treatment of human eSCs with SC-79, an Akt activator, restored the reduced migration of eSCs and decidualization under SM conditions. In conclusion, exposure to SM inhibited decidualization in eSCs by decreasing proliferation and migration through Akt/MMP and FOXO3a/autophagic flux. Nature Publishing Group UK 2019-08-20 /pmc/articles/PMC6702225/ /pubmed/31431660 http://dx.doi.org/10.1038/s41598-019-48580-9 Text en © The Author(s) 2019 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/.
spellingShingle Article
Cho, Hye-Jeong
Baek, Mi-Ock
Khaliq, Sana Abdul
Chon, Seung Joo
Son, Kuk Hui
Lee, Sung Ho
Yoon, Mee-Sup
Microgravity inhibits decidualization via decreasing Akt activity and FOXO3a expression in human endometrial stromal cells
title Microgravity inhibits decidualization via decreasing Akt activity and FOXO3a expression in human endometrial stromal cells
title_full Microgravity inhibits decidualization via decreasing Akt activity and FOXO3a expression in human endometrial stromal cells
title_fullStr Microgravity inhibits decidualization via decreasing Akt activity and FOXO3a expression in human endometrial stromal cells
title_full_unstemmed Microgravity inhibits decidualization via decreasing Akt activity and FOXO3a expression in human endometrial stromal cells
title_short Microgravity inhibits decidualization via decreasing Akt activity and FOXO3a expression in human endometrial stromal cells
title_sort microgravity inhibits decidualization via decreasing akt activity and foxo3a expression in human endometrial stromal cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702225/
https://www.ncbi.nlm.nih.gov/pubmed/31431660
http://dx.doi.org/10.1038/s41598-019-48580-9
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