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Loss- and Gain-of-function Approach to Investigate Early Cell Fate Determinants in Preimplantation Mouse Embryos
Published on: June 6, 2016
Blastomere biopsy influences epigenetic reprogramming during early embryo development, which impacts neural
1State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, 210029, China.
Cellular and Molecular Life Sciences : CMLS
|September 17, 2013
Summary
Blastomere biopsy may impair nervous system development, leading to memory deficits and brain changes in offspring. This epigenetic reprogramming issue during early development causes widespread DNA hypomethylation.
Area of Science:
- Developmental Biology
- Neuroscience
- Epigenetics
Background:
- Blastomere biopsy is a technique used in preimplantation genetic diagnosis.
- Long-term effects of blastomere biopsy on offspring neurological function are not well understood.
- Previous studies indicated a risk of memory defects in adult mice after blastomere biopsy.
Purpose of the Study:
- To assess the long-term nervous system function in aged mice that underwent blastomere biopsy.
- To investigate the underlying mechanisms of neural impairment following blastomere biopsy.
- To explore the impact of blastomere biopsy on epigenetic reprogramming, specifically DNA methylation.
Main Methods:
- Comparative analysis of spatial learning, neuron degeneration, and protein expression in aged biopsied mice versus control mice.
- Genome-wide DNA methylation analysis (MeDIP assay) in the brains of adult biopsied mice.
- Analysis of DNA methylation profiles in early-stage embryos (7.5 days postconception) from biopsied and control groups.
- mRNA profiling of early embryos (4.5 days postconception) to assess gene expression related to methylation.
Main Results:
- Aged biopsied mice exhibited poorer spatial learning, increased neuron degeneration, and altered neural protein expression.
- Genome-wide hypomethylation was observed in the brains of adult biopsied mice, with affected genes linked to neural disorders.
- Early-stage biopsied embryos showed global hypomethylation, indicating impaired de novo methylation.
- Reduced expression of de novo methylation genes in biopsied embryos may contribute to the observed hypomethylation.
Conclusions:
- Blastomere biopsy can lead to abnormal neural development and function in offspring.
- Impaired epigenetic reprogramming, specifically de novo methylation, during early embryonic development is a potential mechanism for nervous system impairment.
- The study highlights a link between blastomere biopsy, hypomethylation, and neurological deficits in mice.
