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CBS and MAT2A improve methionine‐mediated DNA synthesis through SAMTOR/mTORC1/S6K1/CAD pathway during embryo implantation

OBJECTIVES: Early pregnancy loss is a major clinical concern in animal and human reproduction, which is largely influenced by embryo implantation. The importance of methionine for embryo implantation is widely neglected. MATERIALS AND METHODS: We performed a series of experiments with primiparous ra...

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Autores principales: Cai, Shuang, Ye, Qianhong, Zeng, Xiangzhou, Yang, Guangxin, Ye, Changchuan, Chen, Meixia, Yu, Haitao, Wang, Yuming, Wang, Gang, Huang, Shuo, Quan, Shuang, Zeng, Xiangfang, Qiao, Shiyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791180/
https://www.ncbi.nlm.nih.gov/pubmed/33179842
http://dx.doi.org/10.1111/cpr.12950
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author Cai, Shuang
Ye, Qianhong
Zeng, Xiangzhou
Yang, Guangxin
Ye, Changchuan
Chen, Meixia
Yu, Haitao
Wang, Yuming
Wang, Gang
Huang, Shuo
Quan, Shuang
Zeng, Xiangfang
Qiao, Shiyan
author_facet Cai, Shuang
Ye, Qianhong
Zeng, Xiangzhou
Yang, Guangxin
Ye, Changchuan
Chen, Meixia
Yu, Haitao
Wang, Yuming
Wang, Gang
Huang, Shuo
Quan, Shuang
Zeng, Xiangfang
Qiao, Shiyan
author_sort Cai, Shuang
collection PubMed
description OBJECTIVES: Early pregnancy loss is a major clinical concern in animal and human reproduction, which is largely influenced by embryo implantation. The importance of methionine for embryo implantation is widely neglected. MATERIALS AND METHODS: We performed a series of experiments with primiparous rats fed diets containing different levels of methionine during early pregnancy to investigate the role of methionine in embryonic implantation and pregnancy outcomes, and used them to perform in vivo metabolic assessments and in vitro uterine explant culture. In addition, through transcriptome analysis and silencing the expression of cystathionine β‐synthase (CBS, the key enzyme in transsulfuration pathway) and cell adhesion assay, we measured signalling within Ishikawa, pTr and JAR cells. RESULTS: We determined the relevance and underlying mechanism of methionine on embryo implantation. We showed that methionine deprivation sharply decreased embryo implantation sites, expression of CBS and transsulfuration pathway end products, which were reversed by maternal methionine supplementation during early pregnancy. Moreover, we found CBS improved methionine‐mediated cell proliferation and DNA synthesis by CBS inhibition or interference. In addition, transcriptome analysis also revealed that CBS influenced the signalling pathway‐associated cell proliferation and DNA synthesis, as well as a correlation between CBS and methionine adenosyltransferase 2A (MAT2A), implying that MAT2A was possibly involved in cell proliferation and DNA synthesis. Further analysis revealed that MAT2A influenced S‐adenosylmethionine receptor SAMTOR expression, and SAMTOR activated mTORC1 and its downstream S6K1 and CAD, ultimately enhancing DNA synthesis in the embryo and uterus. CONCLUSIONS: Taken together, these studies demonstrate that CBS and MAT2A improve methionine‐mediated DNA synthesis through SAMTOR/mTORC1/S6K1/CAD pathway during embryo implantation.
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spelling pubmed-77911802021-01-11 CBS and MAT2A improve methionine‐mediated DNA synthesis through SAMTOR/mTORC1/S6K1/CAD pathway during embryo implantation Cai, Shuang Ye, Qianhong Zeng, Xiangzhou Yang, Guangxin Ye, Changchuan Chen, Meixia Yu, Haitao Wang, Yuming Wang, Gang Huang, Shuo Quan, Shuang Zeng, Xiangfang Qiao, Shiyan Cell Prolif Original Articles OBJECTIVES: Early pregnancy loss is a major clinical concern in animal and human reproduction, which is largely influenced by embryo implantation. The importance of methionine for embryo implantation is widely neglected. MATERIALS AND METHODS: We performed a series of experiments with primiparous rats fed diets containing different levels of methionine during early pregnancy to investigate the role of methionine in embryonic implantation and pregnancy outcomes, and used them to perform in vivo metabolic assessments and in vitro uterine explant culture. In addition, through transcriptome analysis and silencing the expression of cystathionine β‐synthase (CBS, the key enzyme in transsulfuration pathway) and cell adhesion assay, we measured signalling within Ishikawa, pTr and JAR cells. RESULTS: We determined the relevance and underlying mechanism of methionine on embryo implantation. We showed that methionine deprivation sharply decreased embryo implantation sites, expression of CBS and transsulfuration pathway end products, which were reversed by maternal methionine supplementation during early pregnancy. Moreover, we found CBS improved methionine‐mediated cell proliferation and DNA synthesis by CBS inhibition or interference. In addition, transcriptome analysis also revealed that CBS influenced the signalling pathway‐associated cell proliferation and DNA synthesis, as well as a correlation between CBS and methionine adenosyltransferase 2A (MAT2A), implying that MAT2A was possibly involved in cell proliferation and DNA synthesis. Further analysis revealed that MAT2A influenced S‐adenosylmethionine receptor SAMTOR expression, and SAMTOR activated mTORC1 and its downstream S6K1 and CAD, ultimately enhancing DNA synthesis in the embryo and uterus. CONCLUSIONS: Taken together, these studies demonstrate that CBS and MAT2A improve methionine‐mediated DNA synthesis through SAMTOR/mTORC1/S6K1/CAD pathway during embryo implantation. John Wiley and Sons Inc. 2020-11-12 /pmc/articles/PMC7791180/ /pubmed/33179842 http://dx.doi.org/10.1111/cpr.12950 Text en © 2020 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Cai, Shuang
Ye, Qianhong
Zeng, Xiangzhou
Yang, Guangxin
Ye, Changchuan
Chen, Meixia
Yu, Haitao
Wang, Yuming
Wang, Gang
Huang, Shuo
Quan, Shuang
Zeng, Xiangfang
Qiao, Shiyan
CBS and MAT2A improve methionine‐mediated DNA synthesis through SAMTOR/mTORC1/S6K1/CAD pathway during embryo implantation
title CBS and MAT2A improve methionine‐mediated DNA synthesis through SAMTOR/mTORC1/S6K1/CAD pathway during embryo implantation
title_full CBS and MAT2A improve methionine‐mediated DNA synthesis through SAMTOR/mTORC1/S6K1/CAD pathway during embryo implantation
title_fullStr CBS and MAT2A improve methionine‐mediated DNA synthesis through SAMTOR/mTORC1/S6K1/CAD pathway during embryo implantation
title_full_unstemmed CBS and MAT2A improve methionine‐mediated DNA synthesis through SAMTOR/mTORC1/S6K1/CAD pathway during embryo implantation
title_short CBS and MAT2A improve methionine‐mediated DNA synthesis through SAMTOR/mTORC1/S6K1/CAD pathway during embryo implantation
title_sort cbs and mat2a improve methionine‐mediated dna synthesis through samtor/mtorc1/s6k1/cad pathway during embryo implantation
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791180/
https://www.ncbi.nlm.nih.gov/pubmed/33179842
http://dx.doi.org/10.1111/cpr.12950
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