Wang Meimei, Li Yan, Molenaar Adrian, Li Qiufeng, Cao Yufeng, Shen Yizhao, Chen Panliang, Yan Jinling, Gao Yanxia, Li Jianguo
College of Animal Science and Technology, Hebei Agricultural University, Baoding, Hebei, 071000, China.
College of Veterinary Medicine, Hebei Agricultural University, Baoding, Hebei, 071000, China.
Theriogenology. 2021 Aug;170:91-106. doi: 10.1016/j.theriogenology.2021.04.015. Epub 2021 May 5.
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 (HO) - 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, HSD3β1, 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.
奶牛易患生殖系统疾病，这些疾病被认为与氧化应激有关。在本研究中，我们调查了维生素E（VE）和硒（Se）对过氧化氢（HO）诱导的氧化应激下牛卵巢颗粒细胞增殖、凋亡和类固醇生成的影响，并阐述了其潜在机制。我们的结果表明，VE或Se可以刺激颗粒细胞增殖，这可能是由于在氧化应激下上调了CCND1的表达并降低了P21水平。VE或Se处理还增加了雌二醇（E2）和孕酮（P4）的分泌，这可能是由于改善了与类固醇生成相关基因（StAR、HSD3β1和CYP19A1）的表达。VE或Se处理下调了凋亡相关基因（BAX、CASP3）的表达并减少了细胞凋亡。此外，VE或Se处理抑制了活性氧（ROS）和丙二醛（MDA）的生成，增加了总抗氧化能力（T-AOC）以及超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px）的活性。此外，VE或Se处理还减轻了内质网应激，激活了核因子红细胞2相关因子2（NRF2），并上调了其下游基因包括NQO1、HO-1、GCLM、GCLC的表达。更重要的是，与单独使用VE或Se处理相比，它们的联合处理对氧化损伤显示出更好的保护作用。总体而言，我们的结果表明，VE和Se协同刺激颗粒细胞增殖和类固醇生成，减少细胞凋亡，通过激活NRF2信号通路减轻内质网应激。
