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 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; Biological properties; Blastocyst - drug effects; Blastocyst - metabolism; Cleavage Stage, Ovum - cytology; Cleavage Stage, Ovum - metabolism; Deoxyadenosines - biosynthesis; Deoxyadenosines - chemistry; Deoxyadenosines - pharmacology; Embryo, Mammalian - metabolism; Embryonic Development; Embryos; Experiments; Female; Infertility; Laboratory animals; Liver Neoplasms, Experimental - metabolism; Mice; Proteins; Rats; Studies; Thionucleosides - biosynthesis; Thionucleosides - chemistry; Thionucleosides - pharmacology
• ISSN: 0967-1994; 1469-8730
• DOI: 10.1017/S0967199410000158

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.