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Dysregulated Gln-Glu-α-ketoglutarate axis impairs maternal decidualization and increases the risk of recurrent spontaneous miscarriage
Recurrent spontaneous miscarriage (RSM) affects 1%–2% of fertile women worldwide and poses a risk of future pregnancy complications. Increasing evidence has indicated that defective endometrial stromal decidualization is a potential cause of RSM. Here, we perform liquid chromatography with mass spec...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10213857/ https://www.ncbi.nlm.nih.gov/pubmed/37137303 http://dx.doi.org/10.1016/j.xcrm.2023.101026 |
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author | Tang, Linchen Xu, Xiang-Hong Xu, Sha Liu, Zeying He, Qizhi Li, Wenxuan Sun, Jiaxue Shuai, Wen Mao, Jingwen Zhao, Jian-Yuan Jin, Liping |
author_facet | Tang, Linchen Xu, Xiang-Hong Xu, Sha Liu, Zeying He, Qizhi Li, Wenxuan Sun, Jiaxue Shuai, Wen Mao, Jingwen Zhao, Jian-Yuan Jin, Liping |
author_sort | Tang, Linchen |
collection | PubMed |
description | Recurrent spontaneous miscarriage (RSM) affects 1%–2% of fertile women worldwide and poses a risk of future pregnancy complications. Increasing evidence has indicated that defective endometrial stromal decidualization is a potential cause of RSM. Here, we perform liquid chromatography with mass spectrometry (LC-MS)-based metabolite profiling in human endometrial stromal cells (ESCs) and differentiated ESCs (DESCs) and find that accumulated α-ketoglutarate (αKG) derived from activated glutaminolysis contributes to maternal decidualization. Contrarily, ESCs obtained from patients with RSM show glutaminolysis blockade and aberrant decidualization. We further find that enhanced Gln-Glu-αKG flux decreases histone methylation and supports ATP production during decidualization. In vivo, feeding mice a Glu-free diet leads to a reduction of αKG, impaired decidualization, and an increase of fetal loss rate. Isotopic tracing approaches demonstrate Gln-dependent oxidative metabolism as a prevalent direction during decidualization. Our results demonstrate an essential prerequisite of Gln-Glu-αKG flux to regulate maternal decidualization, suggesting αKG supplementation as a putative strategy to rectify deficient decidualization in patients with RSM. |
format | Online Article Text |
id | pubmed-10213857 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-102138572023-05-27 Dysregulated Gln-Glu-α-ketoglutarate axis impairs maternal decidualization and increases the risk of recurrent spontaneous miscarriage Tang, Linchen Xu, Xiang-Hong Xu, Sha Liu, Zeying He, Qizhi Li, Wenxuan Sun, Jiaxue Shuai, Wen Mao, Jingwen Zhao, Jian-Yuan Jin, Liping Cell Rep Med Report Recurrent spontaneous miscarriage (RSM) affects 1%–2% of fertile women worldwide and poses a risk of future pregnancy complications. Increasing evidence has indicated that defective endometrial stromal decidualization is a potential cause of RSM. Here, we perform liquid chromatography with mass spectrometry (LC-MS)-based metabolite profiling in human endometrial stromal cells (ESCs) and differentiated ESCs (DESCs) and find that accumulated α-ketoglutarate (αKG) derived from activated glutaminolysis contributes to maternal decidualization. Contrarily, ESCs obtained from patients with RSM show glutaminolysis blockade and aberrant decidualization. We further find that enhanced Gln-Glu-αKG flux decreases histone methylation and supports ATP production during decidualization. In vivo, feeding mice a Glu-free diet leads to a reduction of αKG, impaired decidualization, and an increase of fetal loss rate. Isotopic tracing approaches demonstrate Gln-dependent oxidative metabolism as a prevalent direction during decidualization. Our results demonstrate an essential prerequisite of Gln-Glu-αKG flux to regulate maternal decidualization, suggesting αKG supplementation as a putative strategy to rectify deficient decidualization in patients with RSM. Elsevier 2023-05-02 /pmc/articles/PMC10213857/ /pubmed/37137303 http://dx.doi.org/10.1016/j.xcrm.2023.101026 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Report Tang, Linchen Xu, Xiang-Hong Xu, Sha Liu, Zeying He, Qizhi Li, Wenxuan Sun, Jiaxue Shuai, Wen Mao, Jingwen Zhao, Jian-Yuan Jin, Liping Dysregulated Gln-Glu-α-ketoglutarate axis impairs maternal decidualization and increases the risk of recurrent spontaneous miscarriage |
title | Dysregulated Gln-Glu-α-ketoglutarate axis impairs maternal decidualization and increases the risk of recurrent spontaneous miscarriage |
title_full | Dysregulated Gln-Glu-α-ketoglutarate axis impairs maternal decidualization and increases the risk of recurrent spontaneous miscarriage |
title_fullStr | Dysregulated Gln-Glu-α-ketoglutarate axis impairs maternal decidualization and increases the risk of recurrent spontaneous miscarriage |
title_full_unstemmed | Dysregulated Gln-Glu-α-ketoglutarate axis impairs maternal decidualization and increases the risk of recurrent spontaneous miscarriage |
title_short | Dysregulated Gln-Glu-α-ketoglutarate axis impairs maternal decidualization and increases the risk of recurrent spontaneous miscarriage |
title_sort | dysregulated gln-glu-α-ketoglutarate axis impairs maternal decidualization and increases the risk of recurrent spontaneous miscarriage |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10213857/ https://www.ncbi.nlm.nih.gov/pubmed/37137303 http://dx.doi.org/10.1016/j.xcrm.2023.101026 |
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