Genome wide abnormal DNA methylome of human blastocyst in assisted reproductive technology.

Guoqiang Li, Yang Yu, Yong Fan, Congru Li, Xiaocui Xu, Jialei Duan, Rong Li, Xiangjin Kang, Xin Ma, Xuepeng Chen, Yuwen Ke, Jie Yan, Ying Lian, Ping Liu, Yue Zhao, Hongcui Zhao, Yaoyong Chen, Xiaofang Sun, Jianqiao Liu, Jie Qiao, Jiang Liu
Author Information
  1. Guoqiang Li: Ministry of Education Key Laboratory of Assisted Reproduction, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Center of Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China; CAS Key Laboratory of Genome Sciences and Information, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, CAS, Beijing 100101, China.
  2. Yang Yu: Ministry of Education Key Laboratory of Assisted Reproduction, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Center of Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China.
  3. Yong Fan: Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.
  4. Congru Li: CAS Key Laboratory of Genome Sciences and Information, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, CAS, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100029, China.
  5. Xiaocui Xu: CAS Key Laboratory of Genome Sciences and Information, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, CAS, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100029, China.
  6. Jialei Duan: CAS Key Laboratory of Genome Sciences and Information, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, CAS, Beijing 100101, China.
  7. Rong Li: Ministry of Education Key Laboratory of Assisted Reproduction, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Center of Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China.
  8. Xiangjin Kang: Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.
  9. Xin Ma: CAS Key Laboratory of Genome Sciences and Information, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, CAS, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100029, China.
  10. Xuepeng Chen: CAS Key Laboratory of Genome Sciences and Information, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, CAS, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100029, China.
  11. Yuwen Ke: CAS Key Laboratory of Genome Sciences and Information, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, CAS, Beijing 100101, China.
  12. Jie Yan: Ministry of Education Key Laboratory of Assisted Reproduction, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Center of Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China.
  13. Ying Lian: Ministry of Education Key Laboratory of Assisted Reproduction, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Center of Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China.
  14. Ping Liu: Ministry of Education Key Laboratory of Assisted Reproduction, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Center of Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China.
  15. Yue Zhao: Ministry of Education Key Laboratory of Assisted Reproduction, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Center of Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China.
  16. Hongcui Zhao: Ministry of Education Key Laboratory of Assisted Reproduction, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Center of Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China.
  17. Yaoyong Chen: Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.
  18. Xiaofang Sun: Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.
  19. Jianqiao Liu: Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.
  20. Jie Qiao: Ministry of Education Key Laboratory of Assisted Reproduction, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Center of Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China. Electronic address: jie.qiao@263.net.
  21. Jiang Liu: CAS Key Laboratory of Genome Sciences and Information, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, CAS, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100029, China. Electronic address: liuj@big.ac.cn.

Abstract

Proper reprogramming of parental DNA methylomes is essential for mammalian embryonic development. However, it is unknown whether abnormal methylome reprogramming occurs and is associated with the failure of embryonic development. Here we analyzed the DNA methylomes of 57 blastocysts and 29 trophectoderm samples with different morphological grades during assisted reproductive technology (ART) practices. Our data reveal that the global methylation levels of high-quality blastocysts are similar (0.30 ± 0.02, mean ± SD), while the methylation levels of low-quality blastocysts are divergent and away from those of high-quality blastocysts. The proportion of blastocysts with a methylation level falling within the range of 0.30 ± 0.02 in different grades correlates with the live birth rate for that grade. Moreover, abnormal methylated regions are associated with the failure of embryonic development. Furthermore, we can use the methylation data of cells biopsied from trophectoderm to predict the blastocyst methylation level as well as to detect the aneuploidy of the blastocysts. Our data indicate that global abnormal methylome reprogramming often occurs in human embryos, and suggest that DNA methylome is a potential biomarker in blastocyst selection in ART.

Keywords

MeSH Term

Aneuploidy
Blastocyst
CpG Islands
DNA Methylation
Genome, Human
Genomics
Humans
Live Birth
Reproductive Techniques, Assisted

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