title: Insufficient maintenance DNA methylation is associated with abnormal embryonic development.
abstract: 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.
authors.affiliation: Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, 1 Xueshi Road, Hangzhou, Zhejiang 310006, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Yin
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Lv
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: He
authors.forename: Yan-Ting
authors.initials: YT
authors.lastname: Wu
authors.forename: Ai-Xia
authors.initials: AX
authors.lastname: Liu
authors.forename: Guo-Lian
authors.initials: GL
authors.lastname: Ding
authors.forename: Min-Yue
authors.initials: MY
authors.lastname: Dong
authors.forename: Fan
authors.initials: F
authors.lastname: Qu
authors.forename: Chen-Ming
authors.initials: CM
authors.lastname: Xu
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Zhu
authors.forename: He-Feng
authors.initials: HF
authors.lastname: Huang
mesh_terms: D000022:Abortion, Spontaneous / Q000209:etiology; D000818:Animals; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000378:metabolism*; D003656:Decidua / Q000201:enzymology; D004195:Disease Models, Animal; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D005333:Fetus / Q000201:enzymology; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy
chemical_list: D015254:DNA Modification Methylases