Protective Effect and Mechanism of Melatonin on Cisplatin-Induced Ovarian Damage in Mice
Chemotherapeutics’ development has enhanced the survival rate of cancer patients; however, adverse effects of chemotherapeutics on ovarian functions cause fertility loss in female cancer patients. Cisplatin (CP), an important chemotherapeutic drug for treating solid tumors, has adversely affected ov...
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MDPI AG
2022-12-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/24/7383 |
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| author | Fen Xing Mengyao Wang Zhiming Ding Junhui Zhang Simin Ding Lingge Shi Qinge Xie Muhammad Jamil Ahmad Zhaolian Wei Liang Tang Dan Liang Yunxia Cao Yajing Liu |
| author_facet | Fen Xing Mengyao Wang Zhiming Ding Junhui Zhang Simin Ding Lingge Shi Qinge Xie Muhammad Jamil Ahmad Zhaolian Wei Liang Tang Dan Liang Yunxia Cao Yajing Liu |
| author_sort | Fen Xing |
| collection | DOAJ |
| description | Chemotherapeutics’ development has enhanced the survival rate of cancer patients; however, adverse effects of chemotherapeutics on ovarian functions cause fertility loss in female cancer patients. Cisplatin (CP), an important chemotherapeutic drug for treating solid tumors, has adversely affected ovarian function. Melatonin (MT) has been shown to have beneficial effects on ovarian function owing to its antioxidative function. In this research, an animal model was established to explore the effect of MT on CP-induced ovarian damage. Immunohistochemical analysis and Western blot were also used to explore its mechanism. This study reported that MT protects mouse ovaries from CP-induced damage. Specifically, MT significantly prevented CP-induced ovarian reserve decline by maintaining AMH and BMP15 levels. We also found that MT ameliorated CP-induced cell cycle disorders by up-regulating CDC2 expression, and inhibited CP-induced ovarian inflammation by decreasing IL-1β and IL-18 levels. Moreover, MT protected the ovary from CP-induced mitochondrial damage, as reflected by restoring mitochondria-related protein expression. Furthermore, CP caused ovarian apoptosis, as indicated by up-regulated BAX expression. MT was also shown to activate the MAPK pathway. Our results showed that MT could ameliorate ovarian damage induced by CP, implying that MT may be a viable alternative to preserve female fertility during CP chemotherapy. |
| first_indexed | 2024-03-09T16:16:55Z |
| format | Article |
| id | doaj.art-7fa435186f234f57acb7fd658e19faad |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T16:16:55Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-7fa435186f234f57acb7fd658e19faad2023-11-24T15:44:40ZengMDPI AGJournal of Clinical Medicine2077-03832022-12-011124738310.3390/jcm11247383Protective Effect and Mechanism of Melatonin on Cisplatin-Induced Ovarian Damage in MiceFen Xing0Mengyao Wang1Zhiming Ding2Junhui Zhang3Simin Ding4Lingge Shi5Qinge Xie6Muhammad Jamil Ahmad7Zhaolian Wei8Liang Tang9Dan Liang10Yunxia Cao11Yajing Liu12Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, ChinaKey Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Education Ministry of China, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, ChinaDepartment of Urology, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, ChinaChemotherapeutics’ development has enhanced the survival rate of cancer patients; however, adverse effects of chemotherapeutics on ovarian functions cause fertility loss in female cancer patients. Cisplatin (CP), an important chemotherapeutic drug for treating solid tumors, has adversely affected ovarian function. Melatonin (MT) has been shown to have beneficial effects on ovarian function owing to its antioxidative function. In this research, an animal model was established to explore the effect of MT on CP-induced ovarian damage. Immunohistochemical analysis and Western blot were also used to explore its mechanism. This study reported that MT protects mouse ovaries from CP-induced damage. Specifically, MT significantly prevented CP-induced ovarian reserve decline by maintaining AMH and BMP15 levels. We also found that MT ameliorated CP-induced cell cycle disorders by up-regulating CDC2 expression, and inhibited CP-induced ovarian inflammation by decreasing IL-1β and IL-18 levels. Moreover, MT protected the ovary from CP-induced mitochondrial damage, as reflected by restoring mitochondria-related protein expression. Furthermore, CP caused ovarian apoptosis, as indicated by up-regulated BAX expression. MT was also shown to activate the MAPK pathway. Our results showed that MT could ameliorate ovarian damage induced by CP, implying that MT may be a viable alternative to preserve female fertility during CP chemotherapy.https://www.mdpi.com/2077-0383/11/24/7383cisplatinmelatoninovarian damageMAPK pathwaymitochondrial function |
| spellingShingle | Fen Xing Mengyao Wang Zhiming Ding Junhui Zhang Simin Ding Lingge Shi Qinge Xie Muhammad Jamil Ahmad Zhaolian Wei Liang Tang Dan Liang Yunxia Cao Yajing Liu Protective Effect and Mechanism of Melatonin on Cisplatin-Induced Ovarian Damage in Mice Journal of Clinical Medicine cisplatin melatonin ovarian damage MAPK pathway mitochondrial function |
| title | Protective Effect and Mechanism of Melatonin on Cisplatin-Induced Ovarian Damage in Mice |
| title_full | Protective Effect and Mechanism of Melatonin on Cisplatin-Induced Ovarian Damage in Mice |
| title_fullStr | Protective Effect and Mechanism of Melatonin on Cisplatin-Induced Ovarian Damage in Mice |
| title_full_unstemmed | Protective Effect and Mechanism of Melatonin on Cisplatin-Induced Ovarian Damage in Mice |
| title_short | Protective Effect and Mechanism of Melatonin on Cisplatin-Induced Ovarian Damage in Mice |
| title_sort | protective effect and mechanism of melatonin on cisplatin induced ovarian damage in mice |
| topic | cisplatin melatonin ovarian damage MAPK pathway mitochondrial function |
| url | https://www.mdpi.com/2077-0383/11/24/7383 |
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