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 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.
Kobayashi
Masayuki
M
Department of Biotechnology, Faculty of Bioresource Sciences, Akita Prefectural University, Akita, Akita 010-0195, Japan. makoba@akita-pu.ac.jp
Saito
Koichi
K
Tamogami
Shigeru
S
Takashima
Junko
J
Kasuga
Kano
K
Kojima
Ikuo
I
D000818:Animals; D001755:Blastocyst / Q000187:drug effects* / Q000378:metabolism; D002970:Cleavage Stage, Ovum / Q000166:cytology / Q000378:metabolism; D003839:Deoxyadenosines / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology*; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D051379:Mice; D051381:Rats; D013872:Thionucleosides / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology*
D003839:Deoxyadenosines; D013872:Thionucleosides; C008500:5'-methylthioadenosine