Role of COX-2/PGE2 signaling pathway in the apoptosis of rat ovarian granulosa cells induced by MEHP
Objective: MEHP, as the metabolite of DEHP, is a widely used environmental endocrine disruptor. Ovarian granulosa cells participate in maintaining the function of ovary and COX2/PGE2 pathway may regulate the function of granulosa cells. We aimed to explore how COX-2/PGE2 pathway affects cell apoptos...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S014765132300221X |
| _version_ | 1811159010505654272 |
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| author | Xu Li Ying Zhu Tianyang Zhao Xueting Zhang Honghao Qian Jia Wang Xiaohan Miao Liting Zhou Na Li Lin Ye |
| author_facet | Xu Li Ying Zhu Tianyang Zhao Xueting Zhang Honghao Qian Jia Wang Xiaohan Miao Liting Zhou Na Li Lin Ye |
| author_sort | Xu Li |
| collection | DOAJ |
| description | Objective: MEHP, as the metabolite of DEHP, is a widely used environmental endocrine disruptor. Ovarian granulosa cells participate in maintaining the function of ovary and COX2/PGE2 pathway may regulate the function of granulosa cells. We aimed to explore how COX-2/PGE2 pathway affects cell apoptosis in ovarian granulosa cells caused by MEHP. Methods: Primary rat ovarian granulosa cells were treated with MEHP (0, 200, 250, 300 and 350 μM) for 48 h. Adenovirus was used for over-expression of COX-2 gene. The cell viability was tested with CCK8 kits. The apoptosis level was tested by flow cytometry. The levels of PGE2 were tested with ELISA kits. The expression levels of COX-2/PGE2 pathway related genes, ovulation-related genes and apoptosis-related genes, were measured with RT-qPCR and Western blot. Results: MEHP decreased the cell viability. After MEHP exposure, the cell apoptosis level increased. The level of PGE2 markedly decreased. The expression levels of COX-2/PGE2 pathway related genes, ovulation-related genes and anti-apoptotic genes decreased; the expression levels of pro-apoptotic genes increased. The apoptosis level was alleviated after over-expression of COX-2, and the level of PGE2 slightly increased. The expression levels of PTGER2 and PTGER4, and the levels of ovulation-related genes increased; the levels of pro-apoptotic genes decreased. Conclusion: MEHP can cause cell apoptosis by down-regulating the levels of ovulation-related genes via COX-2/PGE2 pathway in rat ovarian granulosa cells. |
| first_indexed | 2024-04-10T05:33:56Z |
| format | Article |
| id | doaj.art-d60ff8204e084d32baf46bfb8bcd8288 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-10T05:33:56Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-d60ff8204e084d32baf46bfb8bcd82882023-03-07T04:05:48ZengElsevierEcotoxicology and Environmental Safety0147-65132023-04-01254114717Role of COX-2/PGE2 signaling pathway in the apoptosis of rat ovarian granulosa cells induced by MEHPXu Li0Ying Zhu1Tianyang Zhao2Xueting Zhang3Honghao Qian4Jia Wang5Xiaohan Miao6Liting Zhou7Na Li8Lin Ye9Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, ChinaDepartment of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, ChinaDepartment of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, ChinaDepartment of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, ChinaDepartment of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, ChinaDepartment of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, ChinaDepartment of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, ChinaDepartment of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, ChinaDepartment of Tropical Diseases, The Second Affiliated Hospital of Hainan Medical University, Key Laboratory of Tropical Translational Medicine of Ministry of Education, NHC Key Laboratory of Tropical Disease Control, School of Tropical Medicine, Hainan Medical University, Haikou, Hainan 571199, China; Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, China; Correspondence to: 1163 Xin Min Street, Changchun 130021, China.Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, China; Correspondence to: 1163 Xin Min Street, Changchun 130021, China.Objective: MEHP, as the metabolite of DEHP, is a widely used environmental endocrine disruptor. Ovarian granulosa cells participate in maintaining the function of ovary and COX2/PGE2 pathway may regulate the function of granulosa cells. We aimed to explore how COX-2/PGE2 pathway affects cell apoptosis in ovarian granulosa cells caused by MEHP. Methods: Primary rat ovarian granulosa cells were treated with MEHP (0, 200, 250, 300 and 350 μM) for 48 h. Adenovirus was used for over-expression of COX-2 gene. The cell viability was tested with CCK8 kits. The apoptosis level was tested by flow cytometry. The levels of PGE2 were tested with ELISA kits. The expression levels of COX-2/PGE2 pathway related genes, ovulation-related genes and apoptosis-related genes, were measured with RT-qPCR and Western blot. Results: MEHP decreased the cell viability. After MEHP exposure, the cell apoptosis level increased. The level of PGE2 markedly decreased. The expression levels of COX-2/PGE2 pathway related genes, ovulation-related genes and anti-apoptotic genes decreased; the expression levels of pro-apoptotic genes increased. The apoptosis level was alleviated after over-expression of COX-2, and the level of PGE2 slightly increased. The expression levels of PTGER2 and PTGER4, and the levels of ovulation-related genes increased; the levels of pro-apoptotic genes decreased. Conclusion: MEHP can cause cell apoptosis by down-regulating the levels of ovulation-related genes via COX-2/PGE2 pathway in rat ovarian granulosa cells.http://www.sciencedirect.com/science/article/pii/S014765132300221XMEHPOvarian granulosa cellApoptosisCOX-2/PGE2 |
| spellingShingle | Xu Li Ying Zhu Tianyang Zhao Xueting Zhang Honghao Qian Jia Wang Xiaohan Miao Liting Zhou Na Li Lin Ye Role of COX-2/PGE2 signaling pathway in the apoptosis of rat ovarian granulosa cells induced by MEHP Ecotoxicology and Environmental Safety MEHP Ovarian granulosa cell Apoptosis COX-2/PGE2 |
| title | Role of COX-2/PGE2 signaling pathway in the apoptosis of rat ovarian granulosa cells induced by MEHP |
| title_full | Role of COX-2/PGE2 signaling pathway in the apoptosis of rat ovarian granulosa cells induced by MEHP |
| title_fullStr | Role of COX-2/PGE2 signaling pathway in the apoptosis of rat ovarian granulosa cells induced by MEHP |
| title_full_unstemmed | Role of COX-2/PGE2 signaling pathway in the apoptosis of rat ovarian granulosa cells induced by MEHP |
| title_short | Role of COX-2/PGE2 signaling pathway in the apoptosis of rat ovarian granulosa cells induced by MEHP |
| title_sort | role of cox 2 pge2 signaling pathway in the apoptosis of rat ovarian granulosa cells induced by mehp |
| topic | MEHP Ovarian granulosa cell Apoptosis COX-2/PGE2 |
| url | http://www.sciencedirect.com/science/article/pii/S014765132300221X |
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