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Identification of a 2-cell stage specific inhibitor of the cleavage of preimplantation mouse embryos synthesized by rat hepatoma cells as 5'-deoxy-5'-methylthioadenosine.

Abstract
Rat hepatoma Reuber H-35 cells produce a unique compound designated as Fr.B-25, a 2-cell stage-specific inhibitor of the cleavage of preimplantation mouse embryos cultured in vitro. Here, we identified Fr.B-25 as a purine nucleoside, 5'-deoxy-5'-methylthioadenosine (MTA), by mass spectroscopic analysis. All of the biological activities examined of authentic MTA on the development of mouse zygotes were indistinguishable from those of Fr.B-25. The mechanism of MTA action in the development of preimplantation mouse embryos was probably different from those of hypoxanthine and adenosine, which are well-characterized purine nucleosides that act as inhibitors of the cleavage of mouse 2-cell embryos. From the shared molecular and biological properties of Fr.B-25 and MTA, we concluded that Fr.B-25 is MTA. To the best of our knowledge, this is the first delineation of the effect of MTA on the development of preimplantation mammalian embryos cultured in vitro.
AuthorsMasayuki Kobayashi, Koichi Saito, Shigeru Tamogami, Junko Takashima, Kano Kasuga, Ikuo Kojima
JournalZygote (Cambridge, England) (Zygote) Vol. 19 Issue 2 Pg. 117-25 (May 2011) ISSN: 1469-8730 [Electronic] England
PMID20569511 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Deoxyadenosines
  • Thionucleosides
  • 5'-methylthioadenosine
Topics
  • Animals
  • Blastocyst (drug effects, metabolism)
  • Cleavage Stage, Ovum (cytology, metabolism)
  • Deoxyadenosines (biosynthesis, chemistry, pharmacology)
  • Embryo, Mammalian (metabolism)
  • Embryonic Development
  • Female
  • Liver Neoplasms, Experimental (metabolism)
  • Mice
  • Rats
  • Thionucleosides (biosynthesis, chemistry, pharmacology)

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