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Cellular and Molecular Life Sciences

, Volume 71, Issue 9, pp 1761–1774 | Cite as

Blastomere biopsy influences epigenetic reprogramming during early embryo development, which impacts neural development and function in resulting mice

  • Yibo Wu
  • Zhuo Lv
  • Yang Yang
  • Guoying Dong
  • Yang Yu
  • Yiqiang Cui
  • Man Tong
  • Liu Wang
  • Zuomin Zhou
  • Hui ZhuEmail author
  • Qi ZhouEmail author
  • Jiahao Sha
Research Article

Abstract

Blastomere biopsy is used in preimplantation genetic diagnosis; however, the long-term implications on the offspring are poorly characterized. We previously reported a high risk of memory defects in adult biopsied mice. Here, we assessed nervous function of aged biopsied mice and further investigated the mechanism of neural impairment after biopsy. We found that aged biopsied mice had poorer spatial learning ability, increased neuron degeneration, and altered expression of proteins involved in neural degeneration or dysfunction in the brain compared to aged control mice. Furthermore, the MeDIP assay indicated a genome-wide low methylation in the brains of adult biopsied mice when compared to the controls, and most of the genes containing differentially methylated loci in promoter regions were associated with neural disorders. When we further compared the genomic DNA methylation profiles of 7.5-days postconception (dpc) embryos between the biopsy and control group, we found the whole genome low methylation in the biopsied group, suggesting that blastomere biopsy was an obstacle to de novo methylation during early embryo development. Further analysis on mRNA profiles of 4.5-dpc embryos indicated that reduced expression of de novo methylation genes in biopsied embryos may impact de novo methylation. In conclusion, we demonstrate an abnormal neural development and function in mice generated after blastomere biopsy. The impaired epigenetic reprogramming during early embryo development may be the latent mechanism contributing to the impairment of the nervous system in the biopsied mice, which results in a hypomethylation status in their brains.

Keywords

Blastomere biopsy Neurodegenerative disorders Epigenetic reprogramming DNA methylation Neuron degeneration Assisted reproductive technology (ART) 

Notes

Acknowledgments

We thank Ming Xiao for his technical support during the experiment of brain morphological analysis. We thank Xuejiang Guo for help with the proteomics data analysis. This study was supported by grants from the Major State Basic Research Development Program of China (973 Program) (No. 2012CB944902) and from the National Science Foundation of China (No.31271604).

Supplementary material

18_2013_1466_MOESM1_ESM.docx (53 kb)
Supplementary material 1 (DOCX 52 kb)

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Copyright information

© Springer Basel 2013

Authors and Affiliations

  • Yibo Wu
    • 1
  • Zhuo Lv
    • 2
  • Yang Yang
    • 1
  • Guoying Dong
    • 1
  • Yang Yu
    • 2
  • Yiqiang Cui
    • 1
  • Man Tong
    • 2
  • Liu Wang
    • 2
  • Zuomin Zhou
    • 1
  • Hui Zhu
    • 1
    Email author
  • Qi Zhou
    • 2
    Email author
  • Jiahao Sha
    • 1
  1. 1.State Key Laboratory of Reproductive Medicine, Department of Histology and EmbryologyNanjing Medical UniversityNanjingChina
  2. 2.State Key Laboratory of Reproductive Biology, Institute of ZoologyChinese Academy of SciencesBeijingChina

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