| Autor: |
Liu Q; State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China., Wang L; Centre of Healthy Animal Husbandry, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan 410125, China., An L; State Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China., Liu Y; State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China., Qu H; State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China., Huang S; State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China., Zhao L; State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China., Yin Y; Centre of Healthy Animal Husbandry, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan 410125, China., Ma Q; State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China. |
| Abstrakt: |
A study aimed to investigate the signaling pathway of zearalenone (ZEA) leading to the apoptosis of ovarian granulosa cells (GCs) and explore the potential of vitamin E (VE) in alleviating ZEA-induced apoptosis of GCs. We constructed an apoptosis model for GCs based on exposure to the environmental toxin ZEA. Transcriptome analysis revealed that ZEA induced endoplasmic reticulum stress by activating the ATF4-Chop pathway. The addition of inhibitors targeting the estrogen receptor (ER) demonstrated that ZEA activates the ATF4-Chop pathway through ER-beta. As a strong antioxidant, VE is thought to mitigate ZEA-induced toxicity. Interestingly, molecular docking analysis at the PERK active site of the endoplasmic reticulum stress revealed a high binding capacity of VE. VE supplementation reduced apoptosis in GCs and decreased the expression of p-eIF-2α, ATF4, and Chop. Mouse tests also demonstrated that VE supplementation effectively mitigated ovarian dysfunction induced by ZEA, as evidenced by increased body weight gain, reduced oxidative stress, and decreased cell death. In summary, the present study demonstrates that ZEA activates the PERK-eIF-2α-ATF4-Chop pathway through ERβ, leading to endoplasmic reticulum stress and apoptosis of GCs. Conversely, VE inhibits the PERK/eIF-2α/ATF4/Chop signaling pathways, mitigating endoplasmic reticulum stress and improving ZEA-induced reproductive toxicity. |
