Changes in histone acetylation during oocyte meiotic maturation in the diabetic mouse
Changes in histone acetylation during oocyte meiotic maturation in the diabetic mouse
复制标题
糖尿病小鼠卵母细胞减数分裂成熟过程中组蛋白乙酰化的变化
DOI：
10.1016/j.theriogenology.2012.03.026
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发表时间：
2012-09-01
期刊：
影响因子：
2.8
通讯作者：
Wang, H. -L.
中科院分区：
文献类型：
--
作者：
Ding, L.;Pan, R.;Wang, H. -L.
虽然有相当多的证据表明，糖尿病会对哺乳动物卵母细胞减数分裂产生不利影响，但糖尿病环境中卵母细胞的乙酰化状态仍不清楚。目的是确定对照组和糖尿病小鼠卵母细胞减数分裂过程中不同阶段H3 K9、H3 K14、H4 K5、H4 K8、H4 K12和H4 K16位点的乙酰化或脱乙酰化模式（基于免疫染色）。根据定量真实的时间聚合酶链反应（qPCR），Gcn 5的平均+/- SEM相对表达（中期[M]I时为1.70 +/- 0.14，MIII时为1.27 +/- 0.01），Ep 300（MI为1.74 +/- 0.04，MII为1.80 +/- 0.001）和Pcaf糖尿病小鼠卵母细胞中的mRNA（MI为2.01 ± 0.03，MII为1.41 ± 0.18）高于对照组而在生殖泡（GV）期，两组之间无差异（P > 0.05）（Gcn 5为1.23 ± 0.04，Ep 300为0.82 ± 0.06，Pcaf为0.80 ± 0.07）。相反，在胚泡期，糖尿病小鼠卵母细胞中Hdac 1、Hdac 2、Hdac 3、Sirt 1和Sirt 2的相对mRNA表达浓度较低（Hdac 1为0.24 ± 0.03，Hdac 2为0.11 ± 0.001，Hdac 3为0.31 ± 0.03，Sirt 1为0.28 ± 0.02，Sirt 2为0.55 ± 0.02; P < 0.05）。类似地，这些基因在MI期的表达浓度在来自糖尿病小鼠的卵母细胞中较低（Hdac 1为0.79 +/- 0.12，Hdac 2为0.72 +/-0.001，Sirt 1为0.02 +/- 0.001，Sirt 2为0.84 +/- 0.08; P < 0.05）。它们在ME期的表达浓度在糖尿病小鼠的卵母细胞中也较低（Hdac 1为0.46 +/- 0.03，Hdac 2为0.93 +/- 0.01，Hdac 3为0.56 +/- 0.01，Sirt 1为0.01 +/- 0.002，Sirt 2为0.84 +/- 0.04; P < 0.05）。但在MI期，两组卵母细胞Hdac 3的表达无差异（0.96 ± 0.03; P > 0.05）。总之，糖尿病改变了细胞内组蛋白修饰系统，这可能导致组蛋白乙酰化的变化，并可能参与糖尿病患者卵母细胞成熟率的降低。(C)2012 Elsevier Inc. All rights reserved.
Although there is considerable evidence that diabetes can adversely affect meiosis in mammalian oocytes, acetylation status of oocytes in a diabetic environment remains unclear. The objective was to determine acetylation or deacetylation patterns (based on immunostaining) of H3K9, H3K14, H4K5, H4K8, H4K12, and H4K16 sites at various stages during meiosis in murine oocytes from control and diabetic mice. According to quantitative real time polymerase chain reaction (qPCR), mean +/- SEM relative expression of Gcn5 (1.70 +/- 0.14 at metaphase [M]I and 1.27 +/- 0.01 at MIII, respectively), Ep300 (1.74 +/- 0.04 at MI and 1.80 +/- 0.001 at MII), and Pcaf (2.01 +/- 0.03 at MI and 1.41 +/- 0.18 at MII) mRNA in oocytes from diabetic mice were higher than those from controls (P < 0.05), whereas there was no difference (P > 0.05) during the germinal vesicle (GV) stage between the two groups (1.23 +/- 0.04 for Gcn5, 0.82 +/- 0.06 for Ep300, and 0.80 +/- 0.07 for Pcaf). Conversely, relative mRNA expression concentrations of Hdac1, Hdac2, Hdac3, Sirt1 and Sirt2 during the germinal vesicle stage were lower in oocytes of diabetic mice (0.24 +/- 0.03 for Hdac1, 0.11 +/- 0.001 for Hdac2, 0.31 +/- 0.03 for Hdac3, 0.28 +/- 0.02 for Sirt1, and 0.55 +/- 0.02 for Sirt2; P < 0.05). Similarly, the expression concentrations of these genes at the MI stage were lower in oocytes from diabetic mice (0.79 +/- 0.12 for Hdac1, 0.72 +/- 0.001 for Hdac2, 0.02 +/- 0.001 for Sirt1, and 0.84 +/- 0.08 for Sirt2; P < 0.05). Their expression concentrations at the ME stage were also lower in oocytes from diabetic mice (0.46 +/- 0.03 for Hdac1, 0.93 +/- 0.01 for Hdac2, 0.56 +/- 0.01 for Hdac3, 0.01 +/- 0.002 for Sirt1, and 0.84 +/- 0.04 for Sirt2; P < 0.05). At the MI stage, however, there was no difference in the expression of Hdac3 between the two groups of oocytes (0.96 +/- 0.03; P > 0.05). Taken together, diabetes altered the intracellular histone modification system, which may have contributed to changes in histone acetylation, and may be involved in the compromised maturation rate of oocytes in diabetic humans. (C) 2012 Elsevier Inc. All rights reserved.