DNA methyltransferase expression in the human endometrium: down-regulation by progesterone and estrogen
DNA methyltransferase expression in the human endometrium: down-regulation by progesterone and estrogen
复制标题
DOI：
10.1093/humrep/dep015
复制
发表时间：
2009-05-01
影响因子：
6.1
通讯作者：
Sugino, Norihiro
中科院分区：
文献类型：
--
作者：
Yamagata, Yoshiaki;Asada, Hiromi;Sugino, Norihiro
表观遗传调控可能参与人类子宫内膜正常周期性变化期间基因表达的调节。我们研究了月经周期期间子宫内膜中 DNA 甲基转移酶 (DNMT) 的表达，以及性类固醇激素对培养的子宫内膜基质细胞 (ESC) 中 DNMT 的影响。通过免疫组织化学和实时 RT-PCR 评估子宫内膜组织（n = 42 名女性）中 DNMT1、DNMT3a 和 DNMT3b 的表达。将 ESC（n = 3 名女性）与雌二醇和醋酸甲羟孕酮 (E + MPA) 一起培养 17 天，并通过实时 RT-PCR 测量 DNMT mRNA 水平。在月经周期的每个阶段，对上皮细胞和基质细胞的细胞核进行 DNMT1、DNMT3a 和 DNMT3b 免疫染色。分泌中期DNMT1和DNMT3a mRNA的组织水平显着低于增殖期（P < 0.01）。对于 DNMT3b，mRNA 水平的变化显示出与 DNMT3a 相似的趋势。在ESC培养中，第8天和第17天，E + MPA处理显着降低了DNMT3a和DNMT3b mRNA水平（分别为P < 0.01和P < 0.05）。在分泌期，人子宫内膜中的DNMT mRNA下降，并且E + MPA下调了培养的ESC中的DNMT3a和DNMT3b mRNA。这些结果表明 DNMT 在与蜕膜化相关的基因表达中具有调节功能。
Epigenetic regulation may be involved in modulation of gene expression during the normal cyclic changes of the human endometrium. We investigated expression of DNA methyltransferases (DNMTs) in endometrium during the menstrual cycle and the influence of sex steroid hormones on DNMT in endometrial stromal cells (ESC) in culture.Expression of DNMT1, DNMT3a and DNMT3b was assessed by immunohistochemistry and real-time RT-PCR in endometrial tissue (n = 42 women). ESC (n = 3 women) were cultured with estradiol and medroxyprogesterone acetate (E + MPA) for 17 days, and DNMT mRNA levels were measured by real-time RT-PCR.Nuclei of both epithelial and stromal cells immunostained for DNMT1, DNMT3a and DNMT3b during each phase of the menstrual cycle. Tissue levels of DNMT1 and DNMT3a mRNA were significantly lower in the mid-secretory phase than in the proliferative phase (P < 0.01). For DNMT3b, the change in mRNA levels showed a similar trend to that for DNMT3a. In ESC culture, DNMT3a and DNMT3b mRNA levels were significantly decreased by E + MPA treatment (P < 0.01 and P < 0.05, respectively) at Day 8 and Day 17.DNMT mRNAs declined in the human endometrium during the secretory phase, and E + MPA down-regulated DNMT3a and DNMT3b mRNAs in ESC in culture. These results suggest that DNMTs have regulatory functions in gene expression that is associated with decidualization.