Neonatal Exposure to Diethylstilbestrol Alters Expression of DNA Methyltransferases and Methylation of Genomic DNA in the Mouse Uterus
Neonatal Exposure to Diethylstilbestrol Alters Expression of DNA Methyltransferases and Methylation of Genomic DNA in the Mouse Uterus
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DOI：
10.1507/endocrj.k08e-239
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发表时间：
2009-02-01
影响因子：
2
通讯作者：
Mori, Chisato
中科院分区：
文献类型：
--
作者：
Sato, Koji;Fukata, Hideki;Mori, Chisato
围产期接触己烯雌酚 (DES) 会对以后的生殖器官产生许多不利影响，例如阴道透明细胞腺癌。该机制可能涉及包括 DNA 甲基化在内的表观遗传过程。我们向新生 C57BL/6 小鼠皮下注射 DES。在第5、14和30天，检查DNA甲基转移酶（Dnmts）Dnmt1、Dnmt3a和Dnmt3b以及转录因子Sp1和Sp3的表达。我们还进行了限制性标志基因组扫描 (RLGS) 以检测异常 DNA 甲基化。实时 RTPCR 显示，DES 处理的小鼠中 Dnmt1、Dnmt3b 和 Sp3 的表达在第 5 天时下降，Dnmt1、Dnmt3a 和 Sp1 的表达在第 14 天时也下降。RLGS 分析显示 5 个基因组位点被 DES 处理去甲基化，另外 5 个位点被甲基化。克隆了两个基因座，并对差异 DNA 甲基化进行了定量。我们的结果表明 DES 改变了 Dnmts 和 DNA 甲基化的表达水平。
Perinatal exposure to diethylstilbestrol (DES) can have numerous adverse effects on the reproductive organs later in life, Such as vaginal clear-cell adenocarcinoma. Epigenetic processes including DNA methylation may be involved in the mechanisms. We subcutaneously injected DES to neonatal C57BL/6 mice. At days 5, 14, and 30, expressions of DNA methyltransferases (Dnmts) Dnmt1, Dnmt3a, and Dnmt3b, and transcription factors Sp1 and Sp3 were examined. We also performed restriction landmark genomic scanning (RLGS) to detect aberrant DNA methylation. Real-time RTPCR revealed that expressions of Dnmt1, Dnmt3b, and Sp3 were decreased at day 5 in DES-treated mice, and that those of Dnmt1, Dnmt3a, and Sp1 were also decreased at day 14. RLGS analysis revealed that 5 genomic loci were demethylated, and 5 other loci were methylated by DES treatment. Two loci were cloned, and differential DNA methylation was quantified. Our results indicated that DES altered the expression levels of Dnmts and DNA methylation.