Purine-induced block to mouse embryo cleavage is reversed by compounds that elevate cyclic adenosine monophosphate

The second or third cleavage of mouse embryos from several strains of females is blocked in the presence of hypoxanthine. To begin to determine the mechanism of the block, we studied several aspects of cell metabolism in blocked embryos, including the stage of the cell cycle and the levels of transcription, translation, and protein phosphorylation. In addition, we attempted to reverse the block by transfer of cytoplasm, transfer of RNAs from dividing cells, and co-culture with compounds that elevate cAMP. Our results indicate the following: 1) that the embryos were blocked in interphase; 2) the expression of lac Z linked to SV40 promoter was depressed, but not blocked; 3) overall protein synthesis was depressed but the appearance of early embryonic proteins was not blocked; 4) overall phosphorylation of proteins was not affected; 5) microinjection of additional cytoplasm from non-blocking embryos did not reverse the block; and 6) compounds that elevate cAMP did reverse the block. Thus, the purines apparently do not prevent early embryonic gene expression or most phosphorylation events, but do inhibit a critical cell process occurring during interphase of the cell cycle that can be compensated by elevations in cAMP.