Maternal Diabetes Causes Alterations of DNA Methylation Statuses of Some Imprinted Genes in Murine Oocytes
Maternal Diabetes Causes Alterations of DNA Methylation Statuses of Some Imprinted Genes in Murine Oocytes
复制标题
母体糖尿病导致小鼠卵母细胞中一些印记基因 DNA 甲基化状态的改变
DOI：
10.1095/biolreprod.112.105981
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发表时间：
2013-05-01
影响因子：
3.6
通讯作者：
Sun, Qing-Yuan
中科院分区：
文献类型：
--
作者：
Ge, Zhao-Jia;Liang, Xing-Wei;Sun, Qing-Yuan
母亲糖尿病不仅对卵母细胞质量有不利影响，而且对胚胎发育也有不利影响。然而，目前还不清楚糖尿病是否会改变卵母细胞中的DNA印记。通过链脲佐菌素(STZ)诱导的和非肥胖糖尿病(NOD)小鼠模型，我们研究了母体糖尿病对卵母细胞印记基因DNA甲基化的影响。以注射链脲佐菌素4d后判定为糖尿病的小鼠为实验动物。在糖尿病小鼠的超排卵母细胞中，Peg3差异甲基化区域(DMR)的甲基化模式受到时间依赖性的影响，在注射STZ后第35天观察到明显的去甲基化。糖尿病卵母细胞中DNA甲基转移酶(DNMT)的表达水平也呈时间依赖性降低。然而，母体糖尿病并未显著改变H19和Snrpn DMRS的甲基化模式，尽管Snrpn发生了一些变化。在NOD小鼠中，Peg3的甲基化模式与STZ诱导的小鼠相似。胚胎发育受到母亲糖尿病的不利影响；然而，在来自糖尿病母亲的雌性后代的卵母细胞中没有观察到明显的印记异常。这些结果表明，母体糖尿病对母系印记基因Peg3的DNA甲基化有时间依赖性的不利影响，但子代卵母细胞的甲基化是正常的。
Maternal diabetes has adverse effects not only on oocyte quality but also on embryo development. However, it is still unknown whether the DNA imprinting in oocytes is altered by diabetes. By using streptozotocin (STZ)-induced and nonobese diabetic (NOD) mouse models we investigated the effect of maternal diabetes on DNA methylation of imprinted genes in oocytes. Mice which were judged as being diabetic 4 days after STZ injection were used for experiments. In superovulated oocytes of diabetic mice, the methylation pattern of Peg3 differential methylation regions (DMR) was affected in a time-dependent manner, and evident demethylation was observed on Day 35 after STZ injection. The expression level of DNA methyltransferases (DNMTs) was also decreased in a time-dependent manner in diabetic oocytes. However, the methylation patterns of H19 and Snrpn DMRs were not significantly altered by maternal diabetes, although there were some changes in Snrpn. In NOD mice, the methylation pattern of Peg3 was similar to that of STZ-induced mice. Embryo development was adversely affected by maternal diabetes; however, no evident imprinting abnormality was observed in oocytes from female offspring derived from a diabetic mother. These results indicate that maternal diabetes has adverse effects on DNA methylation of maternally imprinted gene Peg3 in oocytes of a diabetic female in a time-dependent manner, but methylation in offspring's oocytes is normal.