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

Journal of Animal Science and Biotechnology

Research

Zelin Zhang¹  Qingwang Li¹  Jianyong Cheng¹  Xiaoya Li¹  Li Yang¹  Shiyou Wang¹  Jiaxin Duan²  Rongmao Hua³  Huali Chen⁴ 

[1] College of Animal Science and Technology, Northwest A&F University, 712100, Yangling, People’s Republic of China;College of Animal Science and Technology, Shanxi Agricultural University, 030031, Taigu, People’s Republic of China;College of Pharmacy, Shenzhen Technology University, 518118, Shenzhen, People’s Republic of China;School of Life Science and Engineering, Southwest University of Science and Technology, 621000, Mianyang, People’s Republic of China;

关键词: Apoptosis;    Isorhamnetin;    Oocyte;    Oxidative stress;    Porcine;    Zearalenone;   

DOI  :  10.1186/s40104-022-00809-w

 received in 2022-06-20, accepted in 2022-11-24,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundZearalenone (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.MethodsOocytes 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.ResultsOur 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.ConclusionsCollectively, 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 AbstractA 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.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 1

Fig. 5

Fig. 9

Fig. 5

42004_2023_824_Taba_HTML.png

Fig. 3

40854_2022_440_Article_IEq31.gif

Fig. 1

Fig. 9

Fig. 8