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Human embryonic stem cell methyl cycle enzyme expression: modelling epigenetic programming in assisted reproduction?
William Steele1, Cinzia Allegrucci, Ravinder Singh
1Division of Obstetrics and Gynaecology, University of Nottingham, Queens Medical Centre, Nottingham NG7 2UH, UK.
Reproductive Biomedicine Online
|June 23, 2005
Summary
Altered methyl group metabolism in human embryonic stem cells may cause epigenetic defects. Folate depletion increases homocysteine, suggesting the transsulfuration pathway is key for clearance.
Area of Science:
- Developmental Biology
- Epigenetics
- Biochemistry
Background:
- Epigenetic defects in early development can have lasting consequences.
- Understanding the metabolic pathways influencing embryonic epigenetics is crucial.
Purpose of the Study:
- To investigate the role of methyl group metabolism in inducing epigenetic defects in preimplantation embryos.
- To establish a human embryonic stem cell model for studying these mechanisms.
Main Methods:
- Developed a human embryonic stem cell model.
- Assessed gene expression of key methyl cycle enzymes and methyl group acceptors.
- Induced folate depletion using methotrexate and measured homocysteine levels.
Main Results:
- Demonstrated expression of essential methyl cycle enzymes (e.g., MAT2A, MTHFR) and methyl group acceptors (e.g., DNMTs).
- Observed elevated intracellular homocysteine upon folate depletion, indicating transsulfuration pathway activation.
- Showcased folate receptor alpha expression, suggesting a role for folate metabolism.
Conclusions:
- Altered methyl group metabolism is a potential mechanism for inducing epigenetic changes in preimplantation embryos.
- The transsulfuration pathway plays a role in homocysteine clearance under folate-deficient conditions.