BackgroundThe 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 FindingsFetuses 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/SignificanceIn 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.

Background. This study was aimed at mining crucial long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) for the development of polycystic ovary syndrome (PCOS) based on the coexpression and the competitive endogenous RNA (ceRNA) theories and investigating the underlying therapeutic drugs that may function by reversing the expression of lncRNAs, miRNAs, and mRNAs. Methods. RNA (GSE106724, GSE114419, GSE137684, and GSE138518) or miRNA (GSE84376 and GSE138572) expression profile datasets of PCOS patients were downloaded from the Gene Expression Omnibus database. The weighted gene coexpression network analysis (WGCNA) using four RNA datasets was conducted to construct the lncRNA-mRNA coexpression networks, while the common differentially expressed miRNAs in two miRNA datasets and module RNAs were used to establish the ceRNA network. A protein-protein interaction (PPI) network was created to explore the potential interactions between genes. Gene Ontology and KEGG pathway enrichment analyses were performed to explore the functions of genes in networks. Connectivity Map (CMap) and Comparative Toxicogenomics Database (CTD) analyses were performed to identify potential therapeutic agents for PCOS. Results. Three modules (black, magenta, and yellow) were identified to be PCOS-related after WGCNA analysis, in which KLF3-AS1-PLCG2, MAPKAPK5-AS1-MAP3K14, and WWC2-AS2-TXNIP were important coexpression relationship pairs. WWC2-AS2-hsa-miR-382-PLCG2 was a crucial ceRNA loop in the ceRNA network. The PPI network showed that MAP3K14 and TXNIP could interact with hub genes PLK1 ( degree = 21 ) and TLR1 ( degree = 18 ), respectively. These genes were enriched into mitosis (PLK1), immune response (PLCG2 and TLR1), and cell cycle (TXNIP and PLK1) biological processes. Ten small molecule drugs (especially quercetin) were considered to be therapeutical for PCOS. Conclusion. Our study may provide a novel insight into the mechanisms and therapy for PCOS.

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Monochorionicity, monozygosity, pre-eclampsia were high-risk factors for IUGR in twins. Perinatal death was more prevalent in the non-sIUGR group, and neonatal brain damage was more prevalent in the sIUGR group.

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