Fetal Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guang Dong Province, People's Republic of China.
PLoS One. 2012;7(3):e33503. doi: 10.1371/journal.pone.0033503. Epub 2012 Mar 21.
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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).
CONCLUSIONS/SIGNIFICANCE: 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.
人类内源性逆转录病毒家族 W、Env(C7)、成员 1 基因（HERVWE1）被认为参与滋养细胞融合，其在单胎宫内生长受限胎盘中的表达减少。然而，关于 HERVWE1 在双胎胎儿生长不一致中的作用的信息有限。本研究旨在比较不一致的单卵双胎胎盘之间 HERVWE1 基因表达，并鉴定其甲基化调节。
方法/主要发现：根据出生体重，21 对单卵双绒、不一致的双胞胎胎儿被标记为“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 HERVWE1 mRNA 和蛋白表达谱。使用焦磷酸测序测定 HERVWE1 启动子区域的甲基化谱。通过 RT-PCR 分析 DNA 甲基转移酶（DNMT）转录本水平。使用免疫组织化学染色检测 5-甲基胞嘧啶（5-MC）。双胞胎中 HERVWE1 mRNA 水平与出生体重呈显著负相关（P<0.01）。在不一致的双胞胎中，较小组的 HERVWE1 启动子区域的平均甲基化水平降低（P<0.01），但与较大组相比，较小胎儿的 HERVWE1 mRNA 和蛋白水平升高（P<0.01）。不一致的双胞胎之间 5-MC 染色强度无显著差异（P>0.05）。与较大组相比，较小组的 DNMT3b3 mRNA 水平在不一致的双胞胎中明显下调（P<0.05），而较小组的 DNMT3b7 mRNA 水平在不一致的双胞胎中明显上调（P<0.05）。
结论/意义：在不一致的单卵双绒双胞胎中，较小胎儿的 HERVWE1 表达较高，较大胎儿的表达较低。HERVWE1 基因启动子区域的甲基化可能参与调节不一致双胞胎妊娠中 HERVWE1 基因的表达。
