title: Increased expression and altered methylation of HERVWE1 in the human placentas of smaller fetuses from monozygotic, dichorionic, discordant twins.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: 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.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.forename: Zhiming
authors.initials: Z
authors.lastname: He
authors.forename: Zilian
authors.initials: Z
authors.lastname: Wang
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Luo
authors.forename: Hongyu
authors.initials: H
authors.lastname: Sun
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Linhuan
authors.initials: L
authors.lastname: Huang
authors.forename: Manchao
authors.initials: M
authors.lastname: Li
authors.forename: Qun
authors.initials: Q
authors.lastname: Fang
authors.forename: Shiwen
authors.initials: S
authors.lastname: Jiang
mesh_terms: D000328:Adult; D019175:DNA Methylation; D020077:Endogenous Retroviruses / Q000235:genetics*; D005260:Female; D005333:Fetus / Q000821:virology*; D015967:Gene Expression Regulation, Viral; D006801:Humans; D007150:Immunohistochemistry; D010920:Placenta / Q000378:metabolism / Q000821:virology*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014158:Transcription, Genetic; D014430:Twins, Monozygotic
chemical_list: D012333:RNA, Messenger