miR-484 mediates oxidative stress-induced ovarian dysfunction and promotes granulosa cell apoptosis via SESN2 downregulation
Ovarian dysfunction is a common cause of female infertility, which is associated with genetic, autoimmune and environmental factors. Granulosa cells (GCs) constitute the largest cell population of ovarian follicles. Changes in GCs, including oxidative stress (OS) and excessive reactive oxygen specie...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221323172300085X |
| _version_ | 1797830062531149824 |
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| author | Xiaofei Wang Jiahao Yang Huiying Li Hongbei Mu Ling Zeng Siying Cai Ping Su Huaibiao Li Ling Zhang Wenpei Xiang |
| author_facet | Xiaofei Wang Jiahao Yang Huiying Li Hongbei Mu Ling Zeng Siying Cai Ping Su Huaibiao Li Ling Zhang Wenpei Xiang |
| author_sort | Xiaofei Wang |
| collection | DOAJ |
| description | Ovarian dysfunction is a common cause of female infertility, which is associated with genetic, autoimmune and environmental factors. Granulosa cells (GCs) constitute the largest cell population of ovarian follicles. Changes in GCs, including oxidative stress (OS) and excessive reactive oxygen species (ROS), are involved in regulating ovary function. miR-484 is highly expressed in 3-NP-induced oxidative stress models of ovaries and GCs. miR-484 overexpression aggravated GCs dysfunction and thereby intensified ovarian oxidative stress injury in mice. Moreover, bioinformatic analyses, luciferase assays and pull-down assays indicated that LINC00958 acted as a competing endogenous RNA (ceRNA) for miR-484 and formed a signaling axis with Sestrin2(SESN2) under oxidative stress conditions, which in turn regulated mitochondrial functions and mitochondrial-related apoptosis in GCs. Additionally, the inhibition of miR-484 alleviated GCs dysfunction under ovarian oxidative stress condition. Our present study revealed the role of miR-484 in oxidative stress of ovaries and GCs and the function of LINC00958/miR-484/SESN2 axis in mitochondrial function and mitochondria-related apoptosis. |
| first_indexed | 2024-04-09T13:30:06Z |
| format | Article |
| id | doaj.art-e28f079b51b74f67bdd11ab0533684ee |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-09T13:30:06Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-e28f079b51b74f67bdd11ab0533684ee2023-05-10T04:19:05ZengElsevierRedox Biology2213-23172023-06-0162102684miR-484 mediates oxidative stress-induced ovarian dysfunction and promotes granulosa cell apoptosis via SESN2 downregulationXiaofei Wang0Jiahao Yang1Huiying Li2Hongbei Mu3Ling Zeng4Siying Cai5Ping Su6Huaibiao Li7Ling Zhang8Wenpei Xiang9Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, ChinaInstitute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, ChinaInstitute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, ChinaInstitute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, ChinaMedical Genetics Center, Maternal and Child Health Hospital of Hubei Province, Wuhan, 430070, ChinaInstitute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, ChinaInstitute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China; Wuhan Huake Reproductive Hospital, 128 Sanyang Road, Wuhan, 430013, ChinaInstitute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China; Corresponding author.Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China; Wuhan Huake Reproductive Hospital, 128 Sanyang Road, Wuhan, 430013, China; Corresponding author. Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China; Wuhan Huake Reproductive Hospital, 128 Sanyang Road, Wuhan, 430013, China; Corresponding author. Wuhan Huake Reproductive Hospital, 128 Sanyang Road, Wuhan, 430013, China.Ovarian dysfunction is a common cause of female infertility, which is associated with genetic, autoimmune and environmental factors. Granulosa cells (GCs) constitute the largest cell population of ovarian follicles. Changes in GCs, including oxidative stress (OS) and excessive reactive oxygen species (ROS), are involved in regulating ovary function. miR-484 is highly expressed in 3-NP-induced oxidative stress models of ovaries and GCs. miR-484 overexpression aggravated GCs dysfunction and thereby intensified ovarian oxidative stress injury in mice. Moreover, bioinformatic analyses, luciferase assays and pull-down assays indicated that LINC00958 acted as a competing endogenous RNA (ceRNA) for miR-484 and formed a signaling axis with Sestrin2(SESN2) under oxidative stress conditions, which in turn regulated mitochondrial functions and mitochondrial-related apoptosis in GCs. Additionally, the inhibition of miR-484 alleviated GCs dysfunction under ovarian oxidative stress condition. Our present study revealed the role of miR-484 in oxidative stress of ovaries and GCs and the function of LINC00958/miR-484/SESN2 axis in mitochondrial function and mitochondria-related apoptosis.http://www.sciencedirect.com/science/article/pii/S221323172300085XmiR-484Oxidative stressGranulosa cellsOvarian dysfunctionMitochondriaApoptosis |
| spellingShingle | Xiaofei Wang Jiahao Yang Huiying Li Hongbei Mu Ling Zeng Siying Cai Ping Su Huaibiao Li Ling Zhang Wenpei Xiang miR-484 mediates oxidative stress-induced ovarian dysfunction and promotes granulosa cell apoptosis via SESN2 downregulation Redox Biology miR-484 Oxidative stress Granulosa cells Ovarian dysfunction Mitochondria Apoptosis |
| title | miR-484 mediates oxidative stress-induced ovarian dysfunction and promotes granulosa cell apoptosis via SESN2 downregulation |
| title_full | miR-484 mediates oxidative stress-induced ovarian dysfunction and promotes granulosa cell apoptosis via SESN2 downregulation |
| title_fullStr | miR-484 mediates oxidative stress-induced ovarian dysfunction and promotes granulosa cell apoptosis via SESN2 downregulation |
| title_full_unstemmed | miR-484 mediates oxidative stress-induced ovarian dysfunction and promotes granulosa cell apoptosis via SESN2 downregulation |
| title_short | miR-484 mediates oxidative stress-induced ovarian dysfunction and promotes granulosa cell apoptosis via SESN2 downregulation |
| title_sort | mir 484 mediates oxidative stress induced ovarian dysfunction and promotes granulosa cell apoptosis via sesn2 downregulation |
| topic | miR-484 Oxidative stress Granulosa cells Ovarian dysfunction Mitochondria Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S221323172300085X |
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