Decreased expression of LEF1 caused defective decidualization by inhibiting IL-11 expression in patients with adenomyosis
Abstract Reduced lymphoid enhancer-binding factor 1 (LEF1) expression in patients with adenomyosis during the mid-secretory phase leads to impaired endometrial receptivity, affecting embryo implantation. This study investigated the molecular mechanisms underlying reduced endometrial receptivity in 2...
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| Language: | English |
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BMC
2025-01-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-024-01054-9 |
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| author | Jingru Duan Xiaowei Zhou Hanfei Zhu Mingjuan Zhou Mengyu Liu Yan Zhou Wenzhu Li Bufang Xu Aijun Zhang |
| author_facet | Jingru Duan Xiaowei Zhou Hanfei Zhu Mingjuan Zhou Mengyu Liu Yan Zhou Wenzhu Li Bufang Xu Aijun Zhang |
| author_sort | Jingru Duan |
| collection | DOAJ |
| description | Abstract Reduced lymphoid enhancer-binding factor 1 (LEF1) expression in patients with adenomyosis during the mid-secretory phase leads to impaired endometrial receptivity, affecting embryo implantation. This study investigated the molecular mechanisms underlying reduced endometrial receptivity in 25 adenomyosis patients and 25 controls. Functional experiments were conducted using human endometrial stromal cells (HESCs) and TERT-immortalized HESCs(T-HESCs), with final validation performed using a mouse model. Western blot and quantitative real-time polymerase chain reaction (RT-qPCR) analyses revealed that patients with adenomyosis showed a marked decrease in LEF1 expression in the stromal cells of the endometrium during the mid-secretory phase. In vitro experiments demonstrated that LEF1 knockdown in stromal cells led to impaired decidualization. Transcriptome sequencing, dual-luciferase reporter assays, and chromatin immunoprecipitation (ChIP) experiments showed that LEF1 could bind to the promoter region of interleukin (IL)-11 and promote its transcription, and IL-11 expression was also found to be downregulated in adenomyosis patients. Overexpression of IL-11 rescued the impaired decidualization caused by decreased LEF1 expression. In the in vitro co-culture model, LEF1/IL-11 knockdown led to a reduction in embryo implantation area, which was partially restored upon IL-11 overexpression. In the adenomyosis mouse model, we observed a decrease in LEF1 expression and a reduction in implantation sites compared to control mice, accompanied by impaired decidualization and receptivity. Notably, supplementation with IL-11 restored the number of implantation sites. The decrease in fertility due to reduced endometrial receptivity in adenomyosis patients is a significant clinical issue in assisted reproductive technology. This research provides insights into one potential molecular mechanism underlying this decreased receptivity, with a specific focus on the reduced expression of LEF1 in the endometrial stromal cells during the mid-secretory phase in adenomyosis patients. Our findings offer new perspectives for clinical strategies to improve endometrial receptivity in patients with adenomyosis, potentially enhancing their chances of successful pregnancy. |
| format | Article |
| id | doaj-art-77f386e4cd924773ae57e5cb5b68ab7c |
| institution | Kabale University |
| issn | 1528-3658 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-77f386e4cd924773ae57e5cb5b68ab7c2025-01-12T12:28:11ZengBMCMolecular Medicine1528-36582025-01-0131111510.1186/s10020-024-01054-9Decreased expression of LEF1 caused defective decidualization by inhibiting IL-11 expression in patients with adenomyosisJingru Duan0Xiaowei Zhou1Hanfei Zhu2Mingjuan Zhou3Mengyu Liu4Yan Zhou5Wenzhu Li6Bufang Xu7Aijun Zhang8Department of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineAbstract Reduced lymphoid enhancer-binding factor 1 (LEF1) expression in patients with adenomyosis during the mid-secretory phase leads to impaired endometrial receptivity, affecting embryo implantation. This study investigated the molecular mechanisms underlying reduced endometrial receptivity in 25 adenomyosis patients and 25 controls. Functional experiments were conducted using human endometrial stromal cells (HESCs) and TERT-immortalized HESCs(T-HESCs), with final validation performed using a mouse model. Western blot and quantitative real-time polymerase chain reaction (RT-qPCR) analyses revealed that patients with adenomyosis showed a marked decrease in LEF1 expression in the stromal cells of the endometrium during the mid-secretory phase. In vitro experiments demonstrated that LEF1 knockdown in stromal cells led to impaired decidualization. Transcriptome sequencing, dual-luciferase reporter assays, and chromatin immunoprecipitation (ChIP) experiments showed that LEF1 could bind to the promoter region of interleukin (IL)-11 and promote its transcription, and IL-11 expression was also found to be downregulated in adenomyosis patients. Overexpression of IL-11 rescued the impaired decidualization caused by decreased LEF1 expression. In the in vitro co-culture model, LEF1/IL-11 knockdown led to a reduction in embryo implantation area, which was partially restored upon IL-11 overexpression. In the adenomyosis mouse model, we observed a decrease in LEF1 expression and a reduction in implantation sites compared to control mice, accompanied by impaired decidualization and receptivity. Notably, supplementation with IL-11 restored the number of implantation sites. The decrease in fertility due to reduced endometrial receptivity in adenomyosis patients is a significant clinical issue in assisted reproductive technology. This research provides insights into one potential molecular mechanism underlying this decreased receptivity, with a specific focus on the reduced expression of LEF1 in the endometrial stromal cells during the mid-secretory phase in adenomyosis patients. Our findings offer new perspectives for clinical strategies to improve endometrial receptivity in patients with adenomyosis, potentially enhancing their chances of successful pregnancy.https://doi.org/10.1186/s10020-024-01054-9AdenomyosisLEF1IL-11Endometrial receptivityEndometrial decidualization |
| spellingShingle | Jingru Duan Xiaowei Zhou Hanfei Zhu Mingjuan Zhou Mengyu Liu Yan Zhou Wenzhu Li Bufang Xu Aijun Zhang Decreased expression of LEF1 caused defective decidualization by inhibiting IL-11 expression in patients with adenomyosis Molecular Medicine Adenomyosis LEF1 IL-11 Endometrial receptivity Endometrial decidualization |
| title | Decreased expression of LEF1 caused defective decidualization by inhibiting IL-11 expression in patients with adenomyosis |
| title_full | Decreased expression of LEF1 caused defective decidualization by inhibiting IL-11 expression in patients with adenomyosis |
| title_fullStr | Decreased expression of LEF1 caused defective decidualization by inhibiting IL-11 expression in patients with adenomyosis |
| title_full_unstemmed | Decreased expression of LEF1 caused defective decidualization by inhibiting IL-11 expression in patients with adenomyosis |
| title_short | Decreased expression of LEF1 caused defective decidualization by inhibiting IL-11 expression in patients with adenomyosis |
| title_sort | decreased expression of lef1 caused defective decidualization by inhibiting il 11 expression in patients with adenomyosis |
| topic | Adenomyosis LEF1 IL-11 Endometrial receptivity Endometrial decidualization |
| url | https://doi.org/10.1186/s10020-024-01054-9 |
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