Endogenous folic acid is essential for normal development of preimplantation embryos

Human Reproduction
C O'Neill

Abstract

Preimplantation mammalian embryos develop with a high degree of autonomy. To date, there have been no unequivocal demonstrations of a requirement for vitamins in preimplantation embryo development. Reduced folic acid acts as an important methyl donor in many reactions including the synthesis of thymidine. Thymidine does not accumulate in cells so it might be expected that significant amounts of reduced folate would be required to support the exponential increase in DNA synthesis that occurs during early embryo development. The reduction of folate is catalysed by dihydrofolate reductase (EC 1.5.1.3) which is selectively inhibited by the anti-cancer drug methotrexate. Methotrexate caused a dose-dependent inhibition of cell division in 1-cell, 2-cell and 8-cell mouse embryos with 50% inhibition of division occurring at concentrations of 1-10 microM. At a concentration of 0.1 microM only minimal inhibition of the initial cell division occurred, but continuous culture in this concentration of methotrexate completely inhibited further cell divisions. This suggests that most of the exogenous store of reduced folates was used in the first round of cell division. The effects of methotrexate were apparently primarily due to thymidine sta...Continue Reading

Citations

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