Melatonin attenuates cadmium-induced ovulatory dysfunction by suppressing endoplasmic reticulum stress and cell apoptosis
Abstract Background Increasing evidence demonstrate that cadmium (Cd) has adverse effects on the mammalian reproductive system. However, the mechanisms underlying the effects of Cd on ovarian function and the strategies to reverse these effects have not been fully elucidated. Methods In this study,...
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| Format: | Article |
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BMC
2019-07-01
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| Series: | Reproductive Biology and Endocrinology |
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| Online Access: | http://link.springer.com/article/10.1186/s12958-019-0502-y |
| _version_ | 1828386244593188864 |
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| author | Qingling Yang Jing Zhu Xiaoyan Luo Fangyuan Li Luping Cong Yujiao Wang Yingpu Sun |
| author_facet | Qingling Yang Jing Zhu Xiaoyan Luo Fangyuan Li Luping Cong Yujiao Wang Yingpu Sun |
| author_sort | Qingling Yang |
| collection | DOAJ |
| description | Abstract Background Increasing evidence demonstrate that cadmium (Cd) has adverse effects on the mammalian reproductive system. However, the mechanisms underlying the effects of Cd on ovarian function and the strategies to reverse these effects have not been fully elucidated. Methods In this study, 60 CD-1 mice were divided into four groups (control, melatonin, Cd, Cd with melatonin). During the treatment for 14 days, body weight was measured every 2 days. After the treatment, ovaries were isolated and weighted to observe the morphological and biological characteristics. Statistical analyses were performed using one-way ANOVA followed by Fisher’s-multiple range test or chi-squared test, A P value < 0.05 indicated statistical significance. Results We observed that Cd exposure induced ovulatory dysfunction, demonstrated by the reduced number of ovulated oocytes numbers in the Cd group. However, this endoplasmic reticulum (ER) pathway was activated in the Cd-exposed ovaries and the expression of GRP78, ATF4, CHOP, and p-JNK was upregulated, which was reversed by treatment with melatonin. Furthermore, we found that melatonin inhibited Cd-induced activation of cleaved caspase-3, restored the ratio of Bax/Bcl-2, and ultimately decreased the apoptosis of granular cells as detected by TUNEL staining. Conclusion Collectively, our findings reveal that melatonin attenuated Cd-induced ovulation dysfunction and cell apoptosis by inhibiting the activation of the ER pathway. Thus, melatonin can be a potential agent to protect mammalian ovaries against Cd toxicity. |
| first_indexed | 2024-12-10T05:33:45Z |
| format | Article |
| id | doaj.art-8470eff8cc9d47229aea618e2d1f031a |
| institution | Directory Open Access Journal |
| issn | 1477-7827 |
| language | English |
| last_indexed | 2024-12-10T05:33:45Z |
| publishDate | 2019-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Reproductive Biology and Endocrinology |
| spelling | doaj.art-8470eff8cc9d47229aea618e2d1f031a2022-12-22T02:00:27ZengBMCReproductive Biology and Endocrinology1477-78272019-07-011711810.1186/s12958-019-0502-yMelatonin attenuates cadmium-induced ovulatory dysfunction by suppressing endoplasmic reticulum stress and cell apoptosisQingling Yang0Jing Zhu1Xiaoyan Luo2Fangyuan Li3Luping Cong4Yujiao Wang5Yingpu Sun6Reproductive Medical Center, First Affiliated Hospital of Zhengzhou UniversityReproductive Medical Center, First Affiliated Hospital of Zhengzhou UniversityReproductive Medical Center, First Affiliated Hospital of Zhengzhou UniversityReproductive Medical Center, First Affiliated Hospital of Zhengzhou UniversityReproductive Medical Center, First Affiliated Hospital of Zhengzhou UniversityReproductive Medical Center, First Affiliated Hospital of Zhengzhou UniversityReproductive Medical Center, First Affiliated Hospital of Zhengzhou UniversityAbstract Background Increasing evidence demonstrate that cadmium (Cd) has adverse effects on the mammalian reproductive system. However, the mechanisms underlying the effects of Cd on ovarian function and the strategies to reverse these effects have not been fully elucidated. Methods In this study, 60 CD-1 mice were divided into four groups (control, melatonin, Cd, Cd with melatonin). During the treatment for 14 days, body weight was measured every 2 days. After the treatment, ovaries were isolated and weighted to observe the morphological and biological characteristics. Statistical analyses were performed using one-way ANOVA followed by Fisher’s-multiple range test or chi-squared test, A P value < 0.05 indicated statistical significance. Results We observed that Cd exposure induced ovulatory dysfunction, demonstrated by the reduced number of ovulated oocytes numbers in the Cd group. However, this endoplasmic reticulum (ER) pathway was activated in the Cd-exposed ovaries and the expression of GRP78, ATF4, CHOP, and p-JNK was upregulated, which was reversed by treatment with melatonin. Furthermore, we found that melatonin inhibited Cd-induced activation of cleaved caspase-3, restored the ratio of Bax/Bcl-2, and ultimately decreased the apoptosis of granular cells as detected by TUNEL staining. Conclusion Collectively, our findings reveal that melatonin attenuated Cd-induced ovulation dysfunction and cell apoptosis by inhibiting the activation of the ER pathway. Thus, melatonin can be a potential agent to protect mammalian ovaries against Cd toxicity.http://link.springer.com/article/10.1186/s12958-019-0502-yCadmiumMelatoninOvulationEndoplasmic reticulum (ER) pathway |
| spellingShingle | Qingling Yang Jing Zhu Xiaoyan Luo Fangyuan Li Luping Cong Yujiao Wang Yingpu Sun Melatonin attenuates cadmium-induced ovulatory dysfunction by suppressing endoplasmic reticulum stress and cell apoptosis Reproductive Biology and Endocrinology Cadmium Melatonin Ovulation Endoplasmic reticulum (ER) pathway |
| title | Melatonin attenuates cadmium-induced ovulatory dysfunction by suppressing endoplasmic reticulum stress and cell apoptosis |
| title_full | Melatonin attenuates cadmium-induced ovulatory dysfunction by suppressing endoplasmic reticulum stress and cell apoptosis |
| title_fullStr | Melatonin attenuates cadmium-induced ovulatory dysfunction by suppressing endoplasmic reticulum stress and cell apoptosis |
| title_full_unstemmed | Melatonin attenuates cadmium-induced ovulatory dysfunction by suppressing endoplasmic reticulum stress and cell apoptosis |
| title_short | Melatonin attenuates cadmium-induced ovulatory dysfunction by suppressing endoplasmic reticulum stress and cell apoptosis |
| title_sort | melatonin attenuates cadmium induced ovulatory dysfunction by suppressing endoplasmic reticulum stress and cell apoptosis |
| topic | Cadmium Melatonin Ovulation Endoplasmic reticulum (ER) pathway |
| url | http://link.springer.com/article/10.1186/s12958-019-0502-y |
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