Syncytin-1 is a protein coded by a human endogenous retrovirus (HERV) gene of the HERV-W family (HERVWE1). Syncytin-
1 mediates formation of syncytiotrophoblasts through fusion of cytotrophoblasts, a hallmark of terminal differentiation of placental
trophoblast linage. Syncytin-1 also possesses nonfusogenic functions and regulates cell cycle progression. While decreased syncytin-1
expression and syncytium deficiency are considered important pathological changes in preeclampsia, the molecular mechanism(s) underlying
syncytin-1 downregulation remains unclear. In this study, we confirmed that expression levels of syncytin-1 mRNA and protein
were significantly lower in preeclamptic placentas compared to normal controls. Human chorionic somatomammotropin expression, a
marker for syncytium function, was also decreased in preeclamptic placentas. The mRNA levels of ASCT2, the syncytin-1 receptor involved
in cell fusion process, and GCMa, a transcriptional factor known to regulate syncytin-1 expression, were not significantly altered.
Methylation in the 5’LTR of syncytin-1 promoter was quantified by COBRA, methylation-specific PCR, and DNA sequencing. Results
from all three assays indicated significantly hypermethylated syncytin-1 promoter in preeclamptic placentas compared to normal controls.
Methylation levels were inversely correlated with syncytin-1 mRNA levels, suggesting that hypermethylation may lead to syncytin-1
downregulation. Further experiments indicated that DNMT1 and DNMT3B3 mRNA and protein levels were increased in preeclamptic
placentas, suggesting that higher DNA methyltransferase activity may contribute to the hypermethylation of syncytin-1 in preeclamptic
placentas. These results indicated that aberrant hypermethylation is involved in downregulation of syncytin-1, and epigenetic alterations
may play a significant role in the development of preeclampsia.