Iron overload in endometriosis peritoneal fluid induces early embryo ferroptosis mediated by HMOX1
Abstract Endometriosis is one of the most common disorders that causes infertility in women. Iron is overloaded in endometriosis peritoneal fluid (PF), with harmful effects on early embryo development. However, the mechanism by which endometriosis peritoneal fluid affects embryonic development remai...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-11-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-021-00751-2 |
| _version_ | 1798032039468859392 |
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| author | Shishi Li Yier Zhou Qiongxiao Huang Xiaohua Fu Ling Zhang Fang Gao Zhen Jin Limei Wu Chongyi Shu Xirong Zhang Weihai Xu Jing Shu |
| author_facet | Shishi Li Yier Zhou Qiongxiao Huang Xiaohua Fu Ling Zhang Fang Gao Zhen Jin Limei Wu Chongyi Shu Xirong Zhang Weihai Xu Jing Shu |
| author_sort | Shishi Li |
| collection | DOAJ |
| description | Abstract Endometriosis is one of the most common disorders that causes infertility in women. Iron is overloaded in endometriosis peritoneal fluid (PF), with harmful effects on early embryo development. However, the mechanism by which endometriosis peritoneal fluid affects embryonic development remains unclear. Hence, this study investigated the effect of iron overload on mouse embryos and elucidated the molecular mechanism. Iron overload in endometriosis PF disrupted blastocyst formation, decreased GPX4 expression and induced lipid peroxidation, suggesting that iron overload causes embryotoxicity and induces ferroptosis. Moreover, mitochondrial damage occurs in iron overload-treated embryos, presenting as decreased ATP levels, increased ROS levels and MMP hyperpolarization. The cytotoxicity of iron overload is attenuated by the ferroptosis inhibitor Fer-1. Furthermore, Smart-seq analysis revealed that HMOX1 is upregulated in embryo ferroptosis and that HMOX1 suppresses ferroptosis by maintaining mitochondrial function. This study provides new insight into the mechanism of endometriosis infertility and a potential target for future endometriosis infertility treatment efforts. |
| first_indexed | 2024-04-11T20:06:25Z |
| format | Article |
| id | doaj.art-e08c5e22276946269adac69ff1266fa7 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-04-11T20:06:25Z |
| publishDate | 2021-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-e08c5e22276946269adac69ff1266fa72022-12-22T04:05:18ZengNature Publishing GroupCell Death Discovery2058-77162021-11-017111210.1038/s41420-021-00751-2Iron overload in endometriosis peritoneal fluid induces early embryo ferroptosis mediated by HMOX1Shishi Li0Yier Zhou1Qiongxiao Huang2Xiaohua Fu3Ling Zhang4Fang Gao5Zhen Jin6Limei Wu7Chongyi Shu8Xirong Zhang9Weihai Xu10Jing Shu11Reproductive Medicine Center, Department of Reproductive Endocrinology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical CollegeReproductive Medicine Center, Department of Reproductive Endocrinology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical CollegeReproductive Medicine Center, Department of Reproductive Endocrinology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical CollegeReproductive Medicine Center, Department of Reproductive Endocrinology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical CollegeReproductive Medicine Center, Department of Reproductive Endocrinology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical CollegeReproductive Medicine Center, Department of Reproductive Endocrinology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical CollegeReproductive Medicine Center, Department of Reproductive Endocrinology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical CollegeReproductive Medicine Center, Department of Reproductive Endocrinology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical CollegeReproductive Medicine Center, Department of Reproductive Endocrinology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical CollegeReproductive Medicine Center, Department of Reproductive Endocrinology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical CollegeReproductive Medicine Center, Department of Reproductive Endocrinology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical CollegeReproductive Medicine Center, Department of Reproductive Endocrinology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical CollegeAbstract Endometriosis is one of the most common disorders that causes infertility in women. Iron is overloaded in endometriosis peritoneal fluid (PF), with harmful effects on early embryo development. However, the mechanism by which endometriosis peritoneal fluid affects embryonic development remains unclear. Hence, this study investigated the effect of iron overload on mouse embryos and elucidated the molecular mechanism. Iron overload in endometriosis PF disrupted blastocyst formation, decreased GPX4 expression and induced lipid peroxidation, suggesting that iron overload causes embryotoxicity and induces ferroptosis. Moreover, mitochondrial damage occurs in iron overload-treated embryos, presenting as decreased ATP levels, increased ROS levels and MMP hyperpolarization. The cytotoxicity of iron overload is attenuated by the ferroptosis inhibitor Fer-1. Furthermore, Smart-seq analysis revealed that HMOX1 is upregulated in embryo ferroptosis and that HMOX1 suppresses ferroptosis by maintaining mitochondrial function. This study provides new insight into the mechanism of endometriosis infertility and a potential target for future endometriosis infertility treatment efforts.https://doi.org/10.1038/s41420-021-00751-2 |
| spellingShingle | Shishi Li Yier Zhou Qiongxiao Huang Xiaohua Fu Ling Zhang Fang Gao Zhen Jin Limei Wu Chongyi Shu Xirong Zhang Weihai Xu Jing Shu Iron overload in endometriosis peritoneal fluid induces early embryo ferroptosis mediated by HMOX1 Cell Death Discovery |
| title | Iron overload in endometriosis peritoneal fluid induces early embryo ferroptosis mediated by HMOX1 |
| title_full | Iron overload in endometriosis peritoneal fluid induces early embryo ferroptosis mediated by HMOX1 |
| title_fullStr | Iron overload in endometriosis peritoneal fluid induces early embryo ferroptosis mediated by HMOX1 |
| title_full_unstemmed | Iron overload in endometriosis peritoneal fluid induces early embryo ferroptosis mediated by HMOX1 |
| title_short | Iron overload in endometriosis peritoneal fluid induces early embryo ferroptosis mediated by HMOX1 |
| title_sort | iron overload in endometriosis peritoneal fluid induces early embryo ferroptosis mediated by hmox1 |
| url | https://doi.org/10.1038/s41420-021-00751-2 |
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