Isorhamnetin protects porcine oocytes from zearalenone-induced reproductive toxicity through the PI3K/Akt signaling pathway
Abstract Background Zearalenone (ZEA) widely exists in moldy grains, which seriously destroys the fertility of females. Isorhamnetin, a natural flavonoid, has extensive of pharmacological activities. However, the beneficial effect and the underlying molecular mechanism of isorhamnetin involvement in...
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Journal of Animal Science and Biotechnology |
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| Online Access: | https://doi.org/10.1186/s40104-022-00809-w |
| _version_ | 1811171551915016192 |
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| author | Xiaoya Li Jiaxin Duan Shiyou Wang Jianyong Cheng Huali Chen Zelin Zhang Li Yang Rongmao Hua Qingwang Li |
| author_facet | Xiaoya Li Jiaxin Duan Shiyou Wang Jianyong Cheng Huali Chen Zelin Zhang Li Yang Rongmao Hua Qingwang Li |
| author_sort | Xiaoya Li |
| collection | DOAJ |
| description | Abstract Background Zearalenone (ZEA) widely exists in moldy grains, which seriously destroys the fertility of females. Isorhamnetin, a natural flavonoid, has extensive of pharmacological activities. However, the beneficial effect and the underlying molecular mechanism of isorhamnetin involvement in ZEA-induced porcine oocyte damage have not been investigated. Methods Oocytes were treated with different concentrations of ZEA (3, 5, 8 and 10 μmol/L) and isorhamnetin (5, 10, 20 and 30 μmol/L) for 44 h at 39 ℃. ZEA (5 μmol/L) and isorhamnetin (10 μmol/L) were selected for subsequent studies. Polar body exclusion rate, apoptosis rate and apoptosis related proteins, ROS levels and SOD2 protein, mitochondrial membrane potential and distribution, endoplasmic reticulum distribution and proteins expression, and PI3K, Akt and p-Akt proteins expression of oocytes were detected. In addition, the effect of PI3K antagonist (LY294002) on oocyte nuclear maturation and apoptosis were used to determine the involvement of PI3K/Akt signaling pathway. Results Our findings showed that ZEA exposure damaged oocytes and isorhamnetin therapy restored the developmental capability of porcine oocytes. Isorhamnetin promoted polar body extrusion rate to rescue ZEA-induced meiotic arrest in porcine oocytes. Isorhamnetin alleviated ZEA-induced oxidative stress by stimulating SOD2 protein expression and inhibiting ROS production. Moreover, isorhamnetin enhanced normal mitochondrial distribution and mitochondrial membrane potential to prevent mitochondrial dysfunction induced by ZEA. Changing the expression of endoplasmic reticulum stress-related marker proteins (CHOP, GRP78) and the distribution rate of normal endoplasmic reticulum showed that isorhamnetin relieved ZEA-caused endoplasmic reticulum stress. Mechanistically, isorhamnetin decreased Bax/Bcl-2 protein expression and inhibited ZEA-induced apoptosis through PI3K/Akt signaling pathway. Conclusions Collectively, these results suggest that isorhamnetin protects oocytes from ZEA-caused damage through PI3K/Akt signaling pathway, which enhances meiotic maturation and mitochondrial function, and inhibits early apoptosis, oxidative stress and endoplasmic reticulum stress in porcine oocytes. Our study provides a new strategy for solving the reproductive toxicity induced by ZEA and treating woman infertility. Graphical Abstract A possible mechanism by which isorhamnetin protected porcine oocytes from ZEA-induced damage. Isorhamnetin inhibited meiosis arrest and apoptosis of porcine oocytes induced by ZEA through the PI3K/Akt signaling pathway. Moreover, isorhamnetin repaired ZEA-induced oocyte damage by alleviating oxidative stress, mitochondrial dysfunction and ER stress. |
| first_indexed | 2024-04-10T17:17:01Z |
| format | Article |
| id | doaj.art-29ceee14475e42d19526b938bcab975f |
| institution | Directory Open Access Journal |
| issn | 2049-1891 |
| language | English |
| last_indexed | 2024-04-10T17:17:01Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
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| series | Journal of Animal Science and Biotechnology |
| spelling | doaj.art-29ceee14475e42d19526b938bcab975f2023-02-05T12:20:06ZengBMCJournal of Animal Science and Biotechnology2049-18912023-02-0114111410.1186/s40104-022-00809-wIsorhamnetin protects porcine oocytes from zearalenone-induced reproductive toxicity through the PI3K/Akt signaling pathwayXiaoya Li0Jiaxin Duan1Shiyou Wang2Jianyong Cheng3Huali Chen4Zelin Zhang5Li Yang6Rongmao Hua7Qingwang Li8College of Animal Science and Technology, Northwest A&F UniversityCollege of Animal Science and Technology, Shanxi Agricultural UniversityCollege of Animal Science and Technology, Northwest A&F UniversityCollege of Animal Science and Technology, Northwest A&F UniversitySchool of Life Science and Engineering, Southwest University of Science and TechnologyCollege of Animal Science and Technology, Northwest A&F UniversityCollege of Animal Science and Technology, Northwest A&F UniversityCollege of Pharmacy, Shenzhen Technology UniversityCollege of Animal Science and Technology, Northwest A&F UniversityAbstract Background Zearalenone (ZEA) widely exists in moldy grains, which seriously destroys the fertility of females. Isorhamnetin, a natural flavonoid, has extensive of pharmacological activities. However, the beneficial effect and the underlying molecular mechanism of isorhamnetin involvement in ZEA-induced porcine oocyte damage have not been investigated. Methods Oocytes were treated with different concentrations of ZEA (3, 5, 8 and 10 μmol/L) and isorhamnetin (5, 10, 20 and 30 μmol/L) for 44 h at 39 ℃. ZEA (5 μmol/L) and isorhamnetin (10 μmol/L) were selected for subsequent studies. Polar body exclusion rate, apoptosis rate and apoptosis related proteins, ROS levels and SOD2 protein, mitochondrial membrane potential and distribution, endoplasmic reticulum distribution and proteins expression, and PI3K, Akt and p-Akt proteins expression of oocytes were detected. In addition, the effect of PI3K antagonist (LY294002) on oocyte nuclear maturation and apoptosis were used to determine the involvement of PI3K/Akt signaling pathway. Results Our findings showed that ZEA exposure damaged oocytes and isorhamnetin therapy restored the developmental capability of porcine oocytes. Isorhamnetin promoted polar body extrusion rate to rescue ZEA-induced meiotic arrest in porcine oocytes. Isorhamnetin alleviated ZEA-induced oxidative stress by stimulating SOD2 protein expression and inhibiting ROS production. Moreover, isorhamnetin enhanced normal mitochondrial distribution and mitochondrial membrane potential to prevent mitochondrial dysfunction induced by ZEA. Changing the expression of endoplasmic reticulum stress-related marker proteins (CHOP, GRP78) and the distribution rate of normal endoplasmic reticulum showed that isorhamnetin relieved ZEA-caused endoplasmic reticulum stress. Mechanistically, isorhamnetin decreased Bax/Bcl-2 protein expression and inhibited ZEA-induced apoptosis through PI3K/Akt signaling pathway. Conclusions Collectively, these results suggest that isorhamnetin protects oocytes from ZEA-caused damage through PI3K/Akt signaling pathway, which enhances meiotic maturation and mitochondrial function, and inhibits early apoptosis, oxidative stress and endoplasmic reticulum stress in porcine oocytes. Our study provides a new strategy for solving the reproductive toxicity induced by ZEA and treating woman infertility. Graphical Abstract A possible mechanism by which isorhamnetin protected porcine oocytes from ZEA-induced damage. Isorhamnetin inhibited meiosis arrest and apoptosis of porcine oocytes induced by ZEA through the PI3K/Akt signaling pathway. Moreover, isorhamnetin repaired ZEA-induced oocyte damage by alleviating oxidative stress, mitochondrial dysfunction and ER stress.https://doi.org/10.1186/s40104-022-00809-wApoptosisIsorhamnetinOocyteOxidative stressPorcineZearalenone |
| spellingShingle | Xiaoya Li Jiaxin Duan Shiyou Wang Jianyong Cheng Huali Chen Zelin Zhang Li Yang Rongmao Hua Qingwang Li Isorhamnetin protects porcine oocytes from zearalenone-induced reproductive toxicity through the PI3K/Akt signaling pathway Journal of Animal Science and Biotechnology Apoptosis Isorhamnetin Oocyte Oxidative stress Porcine Zearalenone |
| title | Isorhamnetin protects porcine oocytes from zearalenone-induced reproductive toxicity through the PI3K/Akt signaling pathway |
| title_full | Isorhamnetin protects porcine oocytes from zearalenone-induced reproductive toxicity through the PI3K/Akt signaling pathway |
| title_fullStr | Isorhamnetin protects porcine oocytes from zearalenone-induced reproductive toxicity through the PI3K/Akt signaling pathway |
| title_full_unstemmed | Isorhamnetin protects porcine oocytes from zearalenone-induced reproductive toxicity through the PI3K/Akt signaling pathway |
| title_short | Isorhamnetin protects porcine oocytes from zearalenone-induced reproductive toxicity through the PI3K/Akt signaling pathway |
| title_sort | isorhamnetin protects porcine oocytes from zearalenone induced reproductive toxicity through the pi3k akt signaling pathway |
| topic | Apoptosis Isorhamnetin Oocyte Oxidative stress Porcine Zearalenone |
| url | https://doi.org/10.1186/s40104-022-00809-w |
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