PMID- 34000522 OWN - NLM STAT- MEDLINE DCOM- 20210621 LR - 20210621 IS - 1879-3231 (Electronic) IS - 0093-691X (Linking) VI - 170 DP - 2021 Aug TI - Vitamin E and selenium supplementation synergistically alleviate the injury induced by hydrogen peroxide in bovine granulosa cells. PG - 91-106 LID - S0093-691X(21)00147-3 [pii] LID - 10.1016/j.theriogenology.2021.04.015 [doi] AB - Dairy cows are susceptible to reproductive disorders, which are thought to be associated with oxidative stress. In the study, we investigated the effects of vitamin E (VE) and selenium (Se) on the proliferation, apoptosis, and steroidogenesis in bovine ovarian granulosa cells under hydrogen peroxide (H(2)O(2)) - induced oxidative stress and elaborated the underlying mechanisms. Our results showed that VE or Se could stimulate the granulosa cell proliferation, possibly due to up-regulating the expression of CCND1 and decreasing the P21 levels under oxidative stress. VE or Se treatment also increased the secretion of estradiol (E2) and progesterone (P4), which could be owing to improving the expression of genes associated with steroidogenesis (StAR, HSD3beta1, and CYP19A1) expression. VE or Se treatment down-regulated the apoptosis-related genes (BAX, CASP3) expression and decreased cell apoptosis. Furthermore, VE or Se treatment inhibited reactive oxidative species (ROS) and malondialdehyde (MDA) generation, increased total antioxidant capacity (T-AOC), and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Additionally, VE or Se treatment also alleviated the endoplasmic reticulum stress, activated the nuclear factor erythroid 2-related factor 2 (NRF2), and up-regulated the expression of its downstream genes, including NQO1, HO-1, GCLM, GCLC. More importantly, compared with either VE or Se treatment alone, their combined treatment showed a better protective effect against oxidative damage. Overall, our results indicated that VE and Se synergistically stimulated the granulosa cell proliferation and steroidogenesis, decreased cell apoptosis, mitigated the endoplasmic reticulum stress by activating the NRF2 signal pathway. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Wang, Meimei AU - Wang M AD - College of Animal Science and Technology, Hebei Agricultural University, Baoding, Hebei, 071000, China. FAU - Li, Yan AU - Li Y AD - College of Veterinary Medicine, Hebei Agricultural University, Baoding, Hebei, 071000, China. FAU - Molenaar, Adrian AU - Molenaar A AD - AgResearch Ltd., Grasslands Research Centre, Private Bag 11008, Palmerston North, 4442, New Zealand. FAU - Li, Qiufeng AU - Li Q AD - College of Animal Science and Technology, Hebei Agricultural University, Baoding, Hebei, 071000, China. FAU - Cao, Yufeng AU - Cao Y AD - College of Animal Science and Technology, Hebei Agricultural University, Baoding, Hebei, 071000, China. FAU - Shen, Yizhao AU - Shen Y AD - College of Animal Science and Technology, Hebei Agricultural University, Baoding, Hebei, 071000, China. FAU - Chen, Panliang AU - Chen P AD - College of Animal Science and Technology, Hebei Agricultural University, Baoding, Hebei, 071000, China. FAU - Yan, Jinling AU - Yan J AD - College of Animal Science and Technology, Hebei Agricultural University, Baoding, Hebei, 071000, China. FAU - Gao, Yanxia AU - Gao Y AD - College of Animal Science and Technology, Hebei Agricultural University, Baoding, Hebei, 071000, China. Electronic address: yanxia.gao@hebau.edu.cn. FAU - Li, Jianguo AU - Li J AD - College of Animal Science and Technology, Hebei Agricultural University, Baoding, Hebei, 071000, China. Electronic address: jgli@hebau.edu.cn. LA - eng PT - Journal Article DEP - 20210505 PL - United States TA - Theriogenology JT - Theriogenology JID - 0421510 RN - 0 (Antioxidants) RN - 0 (NF-E2-Related Factor 2) RN - 1406-18-4 (Vitamin E) RN - BBX060AN9V (Hydrogen Peroxide) RN - H6241UJ22B (Selenium) SB - IM MH - Animals MH - Antioxidants/metabolism MH - Apoptosis MH - Cattle MH - Dietary Supplements MH - Female MH - Granulosa Cells/metabolism MH - Hydrogen Peroxide/metabolism MH - NF-E2-Related Factor 2 MH - Oxidative Stress MH - *Selenium/pharmacology MH - Vitamin E/pharmacology OTO - NOTNLM OT - Bovine granulosa cells OT - Oxidative stress OT - Selenium OT - Vitamin E COIS- Declaration of competing interest The authors declare that there is no conflict of interest. EDAT- 2021/05/18 06:00 MHDA- 2021/06/22 06:00 CRDT- 2021/05/17 20:24 PHST- 2021/01/22 00:00 [received] PHST- 2021/04/20 00:00 [revised] PHST- 2021/04/25 00:00 [accepted] PHST- 2021/05/18 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2021/05/17 20:24 [entrez] AID - S0093-691X(21)00147-3 [pii] AID - 10.1016/j.theriogenology.2021.04.015 [doi] PST - ppublish SO - Theriogenology. 2021 Aug;170:91-106. doi: 10.1016/j.theriogenology.2021.04.015. Epub 2021 May 5.