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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

Published online by Cambridge University Press:  23 June 2010

Masayuki Kobayashi*
Affiliation:
Department of Biotechnology, Faculty of Bioresource Sciences, Akita Prefectural University, Akita, Akita 010–0195, Japan.
Koichi Saito
Affiliation:
Department of Biotechnology, Faculty of Bioresource Sciences, Akita Prefectural University, Akita, Akita 010–0195, Japan.
Shigeru Tamogami
Affiliation:
Department of Biological Production, Faculty of Bioresource Sciences, Akita Prefectural University, Akita 010–0195, Japan.
Junko Takashima
Affiliation:
Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama 227–0033, Japan.
Kano Kasuga
Affiliation:
Department of Biotechnology, Faculty of Bioresource Sciences, Akita Prefectural University, Akita, Akita 010–0195, Japan.
Ikuo Kojima
Affiliation:
Department of Biotechnology, Faculty of Bioresource Sciences, Akita Prefectural University, Akita, Akita 010–0195, Japan.
*
All correspondence to: Masayuki Kobayashi, Department of Biotechnology, Faculty of Bioresource Sciences, Akita Prefectural University, Akita, Akita 010–0195, Japan. Fax: +81 18 872 1676. e-mail: makoba@akita-pu.ac.jp

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.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2010

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