Deficiency of Sirtuin 1 Impedes Endometrial Decidualization in Recurrent Implantation Failure Patients
Decidualization is driven by differentiation of human endometrial stromal cells (ESCs), and is a prerequisite for successful implantation and establishment of pregnancy. The critical role of impaired decidualization in women suffered recurrent implantation failure (RIF) has been established, while t...
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| Format: | Article |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.598364/full |
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| author | Jiaxing Li Jiaxing Li Jia Qi Jia Qi Guangxin Yao Guangxin Yao Qinling Zhu Qinling Zhu Xinyu Li Xinyu Li Rui Xu Rui Xu Zhenyi Zhu Zhenyi Zhu Hanting Zhao Hanting Zhao Yuan Wang Yuan Wang Ying Ding Ying Ding Yun Sun Yun Sun |
| author_facet | Jiaxing Li Jiaxing Li Jia Qi Jia Qi Guangxin Yao Guangxin Yao Qinling Zhu Qinling Zhu Xinyu Li Xinyu Li Rui Xu Rui Xu Zhenyi Zhu Zhenyi Zhu Hanting Zhao Hanting Zhao Yuan Wang Yuan Wang Ying Ding Ying Ding Yun Sun Yun Sun |
| author_sort | Jiaxing Li |
| collection | DOAJ |
| description | Decidualization is driven by differentiation of human endometrial stromal cells (ESCs), and is a prerequisite for successful implantation and establishment of pregnancy. The critical role of impaired decidualization in women suffered recurrent implantation failure (RIF) has been established, while the underlying mechanism is poorly understood. In the present study, we verified the essential role of Sirtuin1 (SIRT1) in regulating differentiation and maintaining reactive oxygen species (ROS) homeostasis of human ESCs during decidualization. The abundance of SIRT1 was decreased in RIF patients both in the endometria during window of implantation phase and in the decidualized ESCs. Downregulation of SIRT1 disrupted the intracellular ROS homeostasis during decidualization of ESC, manifested as the accumulation of intracellular ROS level and the reduction of antioxidant stress molecules. Elimination of ROS with N-acetyl-L-cysteine (NAC) could rescued the decidualization inhibition caused by SIRT1 knockdown. Further, we explored the insufficient expression of SIRT1 in ESC affected the deacetylation of forkhead box O1 (FOXO1), and thus inhibited the transcriptional activity of FOXO1. This could account for the dysregulation of intracellular ROS homeostasis during decidualization and decreased expression of decidual markers. Collectively, our findings provided insight into the role of down-regulated SIRT1 in the poor decidual response of ESCs in RIF patients. |
| first_indexed | 2024-12-19T22:59:48Z |
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| id | doaj.art-821af8ed54f04a0e80d93ecdcbbe171f |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-19T22:59:48Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-821af8ed54f04a0e80d93ecdcbbe171f2022-12-21T20:02:32ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-01-01910.3389/fcell.2021.598364598364Deficiency of Sirtuin 1 Impedes Endometrial Decidualization in Recurrent Implantation Failure PatientsJiaxing Li0Jiaxing Li1Jia Qi2Jia Qi3Guangxin Yao4Guangxin Yao5Qinling Zhu6Qinling Zhu7Xinyu Li8Xinyu Li9Rui Xu10Rui Xu11Zhenyi Zhu12Zhenyi Zhu13Hanting Zhao14Hanting Zhao15Yuan Wang16Yuan Wang17Ying Ding18Ying Ding19Yun Sun20Yun Sun21Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, ChinaCenter for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, ChinaCenter for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, ChinaCenter for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, ChinaCenter for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, ChinaCenter for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, ChinaCenter for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, ChinaCenter for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, ChinaCenter for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, ChinaCenter for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, ChinaCenter for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, ChinaDecidualization is driven by differentiation of human endometrial stromal cells (ESCs), and is a prerequisite for successful implantation and establishment of pregnancy. The critical role of impaired decidualization in women suffered recurrent implantation failure (RIF) has been established, while the underlying mechanism is poorly understood. In the present study, we verified the essential role of Sirtuin1 (SIRT1) in regulating differentiation and maintaining reactive oxygen species (ROS) homeostasis of human ESCs during decidualization. The abundance of SIRT1 was decreased in RIF patients both in the endometria during window of implantation phase and in the decidualized ESCs. Downregulation of SIRT1 disrupted the intracellular ROS homeostasis during decidualization of ESC, manifested as the accumulation of intracellular ROS level and the reduction of antioxidant stress molecules. Elimination of ROS with N-acetyl-L-cysteine (NAC) could rescued the decidualization inhibition caused by SIRT1 knockdown. Further, we explored the insufficient expression of SIRT1 in ESC affected the deacetylation of forkhead box O1 (FOXO1), and thus inhibited the transcriptional activity of FOXO1. This could account for the dysregulation of intracellular ROS homeostasis during decidualization and decreased expression of decidual markers. Collectively, our findings provided insight into the role of down-regulated SIRT1 in the poor decidual response of ESCs in RIF patients.https://www.frontiersin.org/articles/10.3389/fcell.2021.598364/fullSIRT1recurrent implantation failure (RIF)decidualizationreactive oxygen species (ROS)endometrial receptivity |
| spellingShingle | Jiaxing Li Jiaxing Li Jia Qi Jia Qi Guangxin Yao Guangxin Yao Qinling Zhu Qinling Zhu Xinyu Li Xinyu Li Rui Xu Rui Xu Zhenyi Zhu Zhenyi Zhu Hanting Zhao Hanting Zhao Yuan Wang Yuan Wang Ying Ding Ying Ding Yun Sun Yun Sun Deficiency of Sirtuin 1 Impedes Endometrial Decidualization in Recurrent Implantation Failure Patients Frontiers in Cell and Developmental Biology SIRT1 recurrent implantation failure (RIF) decidualization reactive oxygen species (ROS) endometrial receptivity |
| title | Deficiency of Sirtuin 1 Impedes Endometrial Decidualization in Recurrent Implantation Failure Patients |
| title_full | Deficiency of Sirtuin 1 Impedes Endometrial Decidualization in Recurrent Implantation Failure Patients |
| title_fullStr | Deficiency of Sirtuin 1 Impedes Endometrial Decidualization in Recurrent Implantation Failure Patients |
| title_full_unstemmed | Deficiency of Sirtuin 1 Impedes Endometrial Decidualization in Recurrent Implantation Failure Patients |
| title_short | Deficiency of Sirtuin 1 Impedes Endometrial Decidualization in Recurrent Implantation Failure Patients |
| title_sort | deficiency of sirtuin 1 impedes endometrial decidualization in recurrent implantation failure patients |
| topic | SIRT1 recurrent implantation failure (RIF) decidualization reactive oxygen species (ROS) endometrial receptivity |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.598364/full |
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