Mechanisms of YAP1-mediated trophoblast ferroptosis in recurrent pregnancy loss
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature..
PURPOSE: The purpose of our study is to investigate the function of YAP1 in the trophoblast ferroptosis and maternal-fetal interface communication of RPL.
METHODS: We collected 25 villous tissues and detected the expression of YAP1. Cell counting kit-8 assay, scratch wound-healing assay, and Matrigel invasion assay were performed to observe the proliferation, migration, and invasion of HTR-8/SVneo and JAR cells. Subsequently, measured the levels of reactive oxygen species (ROS), malondialdehyde (MDA), reduced glutathione (GSH), SLC7A11, SOD2, and GPX4. Ultimately, the use of ferroptosis activator (erastin) and inhibitor (Ferrostatin-1, fer-1) further confirmed the regulation by YAP1. In addition, established an in vitro-induced cell model to study the effect of YAP1 on the decidualization process. Finally, animal models were implemented for further confirmation.
RESULTS: We found that YAP1 was downregulated in RPL patients. Overexpression of YAP1 could significantly enhance the proliferation, migration, and invasion of trophoblasts, and inhibit ferroptosis. Knocking down YAP1 exhibited the opposite effect. Rescue experiments have shown that YAP1 could upregulate the expression of SLC7A11 and GPX4, which are key molecules in the classic pathway of ferroptosis. In addition, the decidualization was impaired when hESCs were treated with conditioned medium of YAP1 knockdown trophoblasts. Moreover, we found that Yap1, Slc7a11, and Gpx4 were downregulated in the RPL mice, along with increased MDA and decreased GSH.
CONCLUSION: Downregulation of YAP1 induces ferroptosis, thereby damaging the trophoblast invasion processes, which also disturbs the communication at the maternal-fetal interface. Our study identified YAP1 as a potential key molecule in the pathogenesis of RPL.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Journal of assisted reproduction and genetics - (2024) vom: 25. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Liping [VerfasserIn] |
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| Links: |
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| Themen: |
Decidualization |
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| Anmerkungen: |
Date Revised 25.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1007/s10815-024-03096-8 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370163397 |
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| 520 | |a © 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. | ||
| 520 | |a PURPOSE: The purpose of our study is to investigate the function of YAP1 in the trophoblast ferroptosis and maternal-fetal interface communication of RPL | ||
| 520 | |a METHODS: We collected 25 villous tissues and detected the expression of YAP1. Cell counting kit-8 assay, scratch wound-healing assay, and Matrigel invasion assay were performed to observe the proliferation, migration, and invasion of HTR-8/SVneo and JAR cells. Subsequently, measured the levels of reactive oxygen species (ROS), malondialdehyde (MDA), reduced glutathione (GSH), SLC7A11, SOD2, and GPX4. Ultimately, the use of ferroptosis activator (erastin) and inhibitor (Ferrostatin-1, fer-1) further confirmed the regulation by YAP1. In addition, established an in vitro-induced cell model to study the effect of YAP1 on the decidualization process. Finally, animal models were implemented for further confirmation | ||
| 520 | |a RESULTS: We found that YAP1 was downregulated in RPL patients. Overexpression of YAP1 could significantly enhance the proliferation, migration, and invasion of trophoblasts, and inhibit ferroptosis. Knocking down YAP1 exhibited the opposite effect. Rescue experiments have shown that YAP1 could upregulate the expression of SLC7A11 and GPX4, which are key molecules in the classic pathway of ferroptosis. In addition, the decidualization was impaired when hESCs were treated with conditioned medium of YAP1 knockdown trophoblasts. Moreover, we found that Yap1, Slc7a11, and Gpx4 were downregulated in the RPL mice, along with increased MDA and decreased GSH | ||
| 520 | |a CONCLUSION: Downregulation of YAP1 induces ferroptosis, thereby damaging the trophoblast invasion processes, which also disturbs the communication at the maternal-fetal interface. Our study identified YAP1 as a potential key molecule in the pathogenesis of RPL | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Decidualization | |
| 650 | 4 | |a Ferroptosis | |
| 650 | 4 | |a Maternal-fetal interface communication | |
| 650 | 4 | |a Recurrent pregnancy loss | |
| 650 | 4 | |a Trophoblast invasion | |
| 650 | 4 | |a YAP1 | |
| 700 | 1 | |a Dai, Fangfang |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yanjie |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Zhidian |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Yanxiang |e verfasserin |4 aut | |
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