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Open Access Research article

Insufficient maintenance DNA methylation is associated with abnormal embryonic development

Li-Jun Yin13, Yu Zhang12, Ping-Ping Lv2, Wei-Hua He13, Yan-Ting Wu1, Ai-Xia Liu1, Guo-Lian Ding2, Min-Yue Dong2, Fan Qu2, Chen-Ming Xu2, Xiao-Ming Zhu2 and He-Feng Huang12*

Author Affiliations

1 Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, 1 Xueshi Road, Hangzhou, Zhejiang 310006, China

2 Key Laboratory of Reproductive Genetics, Ministry of Education, 1 Xueshi Road, Hangzhou, Zhejiang 310006, China

3 Department of Obstetrics and Gynecology, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310003, China

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BMC Medicine 2012, 10:26  doi:10.1186/1741-7015-10-26

Published: 13 March 2012

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.