BACKGROUND: Early pregnancy loss (EPL) is a frustrating clinical problem, whose 
mechanisms are not completely understood. DNA methylation, which includes 
maintenance methylation and de novo methylation directed by DNA 
methyltransferases (DNMTs), is important for embryo development. Abnormal 
function of these DNMTs may have serious consequences for embryonic development.
METHODS: To evaluate the possible involvement of DNA methylation in human EPL, 
the expression of DNMT proteins and global methylation of DNA were assessed in 
villous or decidua from EPL patients. The association of maintenance methylation 
with embryo implantation and development was also examined.
RESULTS: We found that DNMT1 and DNMT3A were both expressed in normal human 
villous and decidua. DNMT1 expression and DNA global methylation levels were 
significantly down-regulated in villous of EPL. DNMT3A expression was not 
significantly changed in the EPL group compared to controls in either villous or 
decidua. We also found that disturbance of maintenance methylation with a DNMT1 
inhibitor may result in a decreased global DNA methylation level and impaired 
embryonic development in the mouse model, and inhibit in vitro embryo attachment 
to endometrial cells.
CONCLUSIONS: Our results demonstrate that defects in DNA maintenance methylation 
in the embryo, not in the mother, are associated with abnormal embryonic 
implantation and development. The findings of the current study provide new 
insights into the etiology of EPL.