Increased expression and altered methylation of HERVWE1 in the human placentas of smaller fetuses from monozygotic, dichorionic, discordant twins.

Increased expression and altered methylation of HERVWE1 in the human placentas of smaller fetuses from monozygotic, dichorionic, discordant twins.
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单卵,二分离,不一致的双胞胎的较小胎儿的人胎盘中Hervwe1的表达和甲基化增加。

DOI:
10.1371/journal.pone.0033503
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Jiang S
Jiang S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Gao Y;He Z;Wang Z;Luo Y;Sun H;Zhou Y;Huang L;Li M;Fang Q;Jiang S

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人内源性逆转录病毒家族W,Env(C7),成员1基因(HERVWE 1)被认为参与滋养层细胞融合,其表达在单胎宫内生长迟缓妊娠的胎盘中减少。然而,关于HERVWE 1在双胞胎不协调胎儿生长中的作用的信息有限。本研究旨在比较HERVWE 1基因在不一致单卵双胞胎胎盘中的表达,并确定其甲基化调控。根据出生体重,将21对同卵、异卵、不一致双胞胎的胎儿标记为“较小”或“较大”。使用定量RT-PCR和免疫组织化学(IHC)染色分析胎盘HERVWE 1 mRNA和蛋白表达谱。使用焦磷酸测序测定分析HERVWE 1启动子区的甲基化谱。通过RT-PCR分析DNA甲基转移酶(DNMT)转录水平。5-甲基胞嘧啶(5-MC)用免疫组织化学分析染色。双生子HERVWE 1 mRNA表达水平与出生体重呈显著负相关(P<0.01)。然而,HERVWE 1启动子区域的平均甲基化水平在不一致双胞胎中较小的组中降低(P<0.01),与较大的胎儿相比,在不一致双胞胎中较小的胎儿中发现HERVWE 1的mRNA和蛋白水平升高(P<0.01)。5-MC染色强度在不一致双生子间差异无统计学意义(P>0.05)。在不一致双生子中,小胎组与大胎组相比,DNMT 3b 3 mRNA水平显著下调(P<0.05),而小胎组与大胎组相比,DNMT 3b 7 mRNA水平显著上调(P<0.05)。在不一致的单卵双胞胎中,HERVWE 1表达在较小的胎儿中较高,在较大的胎儿中较低。HERVWE 1基因启动子区的甲基化可能参与不一致双胎妊娠HERVWE 1基因表达的调节。
The human endogenous retroviral family W, Env(C7), member 1 gene (HERVWE1) is thought to participate in trophoblast cell fusion, and its expression is diminished in the placentas of singleton intrauterine growth-retarded pregnancies. However, there is limited information about the role of HERVWE1 in discordant fetal growth in twins. This study was to compare HERVWE1 gene expression between the placentas of discordant monozygotic twins and to identify its regulation by methylation. Fetuses from twenty-one pairs of monozygotic, dichorionic, discordant twins were marked as “smaller” or “larger” according to birth weight. Placental HERVWE1 mRNA and protein expression profiles were analyzed using quantitative RT-PCR and immunohistochemistry (IHC) staining. Methylation profiles of the HERVWE1 promoter region were analyzed using a pyrosequencing assay. DNA methyltransferase (DNMT) transcript levels were analyzed by RT-PCR. 5-methyl cytosine (5-MC) was stained using an immunohistochemical assay. There was a significant negative correlation between HERVWE1 mRNA levels and birth weight in twins (P<0.01). Whereas the mean methylation level of the HERVWE1 promoter region was diminished in the smaller group in discordant twins(P<0.01), increased mRNA and protein levels of HERVWE1 were found in smaller fetuses compared with larger fetuses in discordant twins(P<0.01). There was no significant difference in 5-MC staining intensity between discordant twins (P>0.05). The DNMT3b3 mRNA levels in the smaller group were significantly downregulated compared with the larger group in discordant twins(P<0.05), whereas the DNMT3b7 mRNA levels in the smaller group were significantly upregulated compared with the larger group in discordant twins(P<0.05). In discordant, monozygotic, dichorionic twins, HERVWE1 expression was higher in smaller fetuses and lower in larger fetuses. Methylation of the HERVWE1 gene promoter region may participate in the regulation of HERVWE1 gene expression in discordant twin pregnancies.
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