SIRT7 functions in redox homeostasis and cytoskeletal organization during oocyte maturation

SIRT7 functions in redox homeostasis and cytoskeletal organization during oocyte maturation
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DOI:
10.1096/fj.201800078rr
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发表时间:
2018-11-01
期刊:
影响因子:
4.8
通讯作者:
Gu, Ling
Gu, Ling
中科院分区:
生物学2区
文献类型:
--
作者:
Gao, Min;Li, Xiaoyan;Gu, Ling

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SIRT 7是sirtuin家族的成员,与辅酶NAD一起催化蛋白质脱乙酰化,并参与多种生物过程;然而,其在哺乳动物卵母细胞中的功能仍有待探索。在这里,我们报告了小鼠卵母细胞中特异性敲低SIRT 7后减数分裂成熟的破坏。特别是,在SIRT 7耗尽的卵母细胞中容易观察到纺锤体/染色体紊乱和皮质肌动蛋白帽的丢失,产生非整倍体卵。此外,我们发现SIRT 7的耗竭显著提高了卵母细胞中的活性氧水平,从而损害了早期胚胎的发育能力。值得注意的是,SIRT 7蛋白水平在来自肥胖小鼠的卵母细胞中显著降低,并且外源SIRT 7的强制表达改善了卵母细胞中与母体肥胖相关的减数分裂缺陷和氧化应激。总之,我们的数据表明SIRT 7是决定卵母细胞质量的重要因素,并且可能介导肥胖对雌性生殖的影响。Li,X.,他,Y.,汉湖,加-地Qiu,D.,林湖,加-地刘洪,刘杰,古湖,加-地SIRT 7在卵母细胞成熟过程中的氧化还原稳态和细胞骨架组织中发挥作用。
SIRT7, a member of the sirtuin family, with coenzyme NAD catalyzes protein deacetylation and has been implicated in multiple biologic processes; however, its function in mammalian oocytes remains to be explored. Here, we report disrupted meiotic maturation upon specific knockdown of SIRT7 in mouse oocytes. In particular, disorganized spindle/chromosomes and the loss of the cortical actin cap are readily observed in SIRT7-depleted oocytes, generating aneuploid eggs. Furthermore, we found that SIRT7 depletion markedly elevated reactive oxygen species levels in oocytes, thereby compromising the developmental competence of early embryos. Of note, SIRT7 protein level is significantly decreased in oocytes from obese mice, and the forced expression of exogenous SIRT7 ameliorates maternal obesity-associated meiotic defects and oxidative stress in oocytes. In summary, our data suggest that SIRT7 is an essential factor in the determination of oocyte quality and may mediate the effects of obesity on female reproduction.Gao, M., Li, X., He, Y., Han, L., Qiu, D., Ling, L., Liu, H., Liu, J., Gu, L. SIRT7 functions in redox homeostasis and cytoskeletal organization during oocyte maturation.