Isorhamnetin protects porcine oocytes from zearalenone-induced reproductive toxicity through the PI3K/Akt signaling pathway

• Published in: 畜牧与生物技术杂志（英文版） Vol. 14; no. 3; pp. 1054 - 1067
• Main Authors: Xiaoya Li, Jiaxin Duan, Shiyou Wang, Jianyong Cheng, Huali Chen, Zelin Zhang, Li Yang, Rongmao Hua, Qingwang Li
• Format: Journal Article
• Language: English
• Published: College of Animal Science and Technology,Northwest A&F University,Yangling 712100,People's Republic of China%College of Animal Science and Technology,Shanxi Agricultural University,Taigu 030031,People's Repub-lic of China%School of Life Science and Engineering,Southwest University of Science and Technology,Mianyang 621000,People's Republic of China%College of Pharmacy,Shenzhen Technology University,Shenzhen 518118,People's Republic of China 2023
• Subjects: Isorhamnetin; Oxidative stress; Porcine; Zearalenone; Oocyte; Apoptosis
• ISSN: 1674-9782; 2049-1891

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 stud-ies.Polar body exclusion rate,apoptosis rate and apoptosis related proteins,ROS levels and SOD2 protein,mitochon-drial 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 devel-opmental 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 endoplas-mic reticulum showed that isorhamnetin relieved ZEA-caused endoplasmic reticulum stress.Mechanistically,isor-hamnetin 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 strat-egy for solving the reproductive toxicity induced by ZEA and treating woman infertility.