Role of the mitochondrial genome during early development in mice. Effects of ethidium bromide and chloramphenicol.
The role of the mitochondrial genome in early development and differentiation was studied in mouse embryos cultured in vitro from the two to four cell stage to the blastocyst (about 100 cells). During this period the mitochondria undergo morphological differentiation: progressive enlargement followed by an increase in matrix density, in number of cristae, and in number of mitochondrial ribosomes. Mitochondrial ribosomal and transfer RNA synthesis occurs from the 8 to 16 cell stage on and contributes to the establishment of a mitochondrial protein-synthesizing system. Inhibition of mitochondrial RNA- and protein-synthesis by 0.1 microg/ml of ethidium bromide or 31.2 microg/ml of chloramphenicol permits essentially normal embryo development and cellular differentiation. Mitochondrial morphogenesis is also nearly normal except for the appearance of dilated and vesicular cristae in blastocyst mitochondria. Such blastocysts are capable of normal postimplantation development when transplanted into the uteri of foster mothers. Higher concentrations of these inhibitors have general toxic effects and arrest embryo development. It is concluded that mitochondrial differentiation in the early mouse embryo occurs through the progressive transformation of the preexisting mitochondria and is largely controlled by the nucleocytoplasmic system. Mitochondrial protein synthesis is required for the normal structural organization of the cristae in blastocyst mitochondria. Embryo development and cellular differentiation up to the blastocyst stage are not dependent on mitochondrial genetic activity.
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002701:Chloramphenicol / Q000494:pharmacology*; D002875:Chromosomes; D005314:Embryonic and Fetal Development; D004996:Ethidium / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009024:Morphogenesis / Q000187:drug effects; D010617:Phenanthridines / Q000494:pharmacology*; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D012335:RNA, Ribosomal / Q000096:biosynthesis; D012343:RNA, Transfer / Q000096:biosynthesis
D010617:Phenanthridines; D012335:RNA, Ribosomal; D012313:RNA; D002701:Chloramphenicol; D012343:RNA, Transfer; D004996:Ethidium