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

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 analy...

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Bibliographic Details
Published in:Zygote (Cambridge) 2011-05, Vol.19 (2), p.117-125
Main Authors: Kobayashi, Masayuki, Saito, Koichi, Tamogami, Shigeru, Takashima, Junko, Kasuga, Kano, Kojima, Ikuo
Format: Article
Language:English
Subjects:
Animals
Blastocyst - drug effects
Blastocyst - metabolism
Cleavage Stage, Ovum - cytology
Cleavage Stage, Ovum - metabolism
Deoxyadenosines - biosynthesis
Deoxyadenosines - chemistry
Deoxyadenosines - pharmacology
Embryo, Mammalian - metabolism
Embryonic Development
Experiments
Female
Infertility
Laboratory animals
Liver Neoplasms, Experimental - metabolism
Mice
Proteins
Rats
Studies
Thionucleosides - biosynthesis
Thionucleosides - chemistry
Thionucleosides - pharmacology
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Summary: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.
ISSN:0967-1994
1469-8730
DOI:10.1017/S0967199410000158