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Background  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.

Increased Expression and Altered Methylation of HERVWE1 in the Human Placentas of Smaller Fetuses from Monozygotic, Dichorionic, Discordant Twins