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论文题目: Melatonin-induced demethylation of antioxidant genes increases antioxidant capacity through ROR alpha in cumulus cells of prepubertal lambs
英文论文题目: Melatonin-induced demethylation of antioxidant genes increases antioxidant capacity through ROR alpha in cumulus cells of prepubertal lambs
第一作者: 房义
英文第一作者: Fa Yi
联系作者: 钟荣珍
英文联系作者: Rong Z.Zhong
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发表年度: 2019
卷: 131
期:
页码: 173-183
摘要:

Physical damage and oxidative stress may occur in prepubertal cumulus cells, due to insufficient glutathione synthesis. To determine potential epigenetic mechanismsrelated to antioxidant effects of melatonin on ovine prepubertal cumulus cells, 30 lambs, 4-wk-old were randomly allocated into two groups: a control (C, n=20) group and a melatonin (M, n=10) group given a subcutaneous implant containing 18mg melatonin. All lambs were superovulated (250 IU FSH and 250 IU eCG). Cumulus cells from germinal vesicle stage cumulus oocyte complexes (COCs) were collected by ovarian follicular aspiration and dissociated with hyaluronidase. Compared to the C group, the M group had greater superovulation, better antioxidant capacity, a higher proportion of fully expanded COCs and a lower proportion of apoptotic cumulus cells (P<0.05). Melatonin up-regulated mRNA expression of genes for melatonin receptors MT1 and nuclear binding site RORα, antioxidants (SOD1, GPx4and CAT) and cumulus cell expansion (PTX3HAS2 and PTGS2), as well as Bcl2, but down-regulated expression of Bax (P<0.05). Regarding epigenetics, there were less methylation at five CpG sites of SOD1, three CpG sites of GPx4 and two CpG sites of CAT in M versus C groups (P< 0.05), leading to lower total methylation of SOD1, GPx4 and CAT promoters region on M group (P<0.05). In a mechanistic study, addition of MT1 or RORα antagonist increased ROS and MDA concentrations, but decreased T-AOC, GPx, CAT and T-SOD concentrations (P<0.05), whereas there were no significant difference between the melatonin and MT2 antagonist treatment groups for T-AOC, GPx, CAT and T-SOD concentrations. Furthermore, addition of RORα agonist decreased total DNA methylation of SOD1, GPx4 and CAT, with no significant difference after MT1 agonist treatment. These studies provided new information regarding epigenetic mechanisms by which melatonin promoted ovine prepubertal cumulus cells antioxidant through RORα, both in vitro and in vivo.

英文摘要:

Physical damage and oxidative stress may occur in prepubertal cumulus cells, due to insufficient glutathione synthesis. To determine potential epigenetic mechanismsrelated to antioxidant effects of melatonin on ovine prepubertal cumulus cells, 30 lambs, 4-wk-old were randomly allocated into two groups: a control (C, n=20) group and a melatonin (M, n=10) group given a subcutaneous implant containing 18mg melatonin. All lambs were superovulated (250 IU FSH and 250 IU eCG). Cumulus cells from germinal vesicle stage cumulus oocyte complexes (COCs) were collected by ovarian follicular aspiration and dissociated with hyaluronidase. Compared to the C group, the M group had greater superovulation, better antioxidant capacity, a higher proportion of fully expanded COCs and a lower proportion of apoptotic cumulus cells (P<0.05). Melatonin up-regulated mRNA expression of genes for melatonin receptors MT1 and nuclear binding site RORα, antioxidants (SOD1, GPx4and CAT) and cumulus cell expansion (PTX3HAS2 and PTGS2), as well as Bcl2, but down-regulated expression of Bax (P<0.05). Regarding epigenetics, there were less methylation at five CpG sites of SOD1, three CpG sites of GPx4 and two CpG sites of CAT in M versus C groups (P< 0.05), leading to lower total methylation of SOD1, GPx4 and CAT promoters region on M group (P<0.05). In a mechanistic study, addition of MT1 or RORα antagonist increased ROS and MDA concentrations, but decreased T-AOC, GPx, CAT and T-SOD concentrations (P<0.05), whereas there were no significant difference between the melatonin and MT2 antagonist treatment groups for T-AOC, GPx, CAT and T-SOD concentrations. Furthermore, addition of RORα agonist decreased total DNA methylation of SOD1, GPx4 and CAT, with no significant difference after MT1 agonist treatment. These studies provided new information regarding epigenetic mechanisms by which melatonin promoted ovine prepubertal cumulus cells antioxidant through RORα, both in vitro and in vivo.

刊物名称: Free Radical Biology and Medicine
英文刊物名称: Free Radical Biology and Medicine
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参与作者: Y. Fang, J. L. Zhang, Y. H. Li, X. F. Guo, J. J. Li, R. Z. Zhong and X. S. Zhang
英文参与作者: Y. Fang, J. L. Zhang, Y. H. Li, X. F. Guo, J. J. Li, R. Z. Zhong and X. S. Zhang