Nucleologenesis in the human embryo developing in vitro: ultrastructural and autoradiographic analysis.

Nucleolar development during cleavage of human embryos in vitro was analyzed using combined autoradiographic and ultrastructural approaches. Human 2- to 4-cell embryos lack functionally active nucleoli. They possess nucleolus-like bodies formed by a homogeneous mass composed of densely packed fine fibrils. The nucleolus-like bodies contain no recently replicated embryonic DNA and do not show any detectable RNA synthesis. Their transformation into nucleoli is a relatively rapid process characterized by progressive infiltration of these bodies by adjacent chromatin, followed by the beginning of RNA synthesis and processing reflected by the appearance of the first nucleolar granules. These changes take place in 6- to 8-cell embryos, probably starting after the third cleavage division. Finally, most frequently in 10- to 12-cell embryos, typical nucleolar structure is established as a result of intranucleolar differentiation giving rise to distinct fibrillar and granular components as well as to nucleolar interstices. It is suggested that this pattern of nucleologenesis, different from that pertinent to mouse embryos (M. Geuskens and H. Alexandre (1984). Cell Differ. 14, 125-134), might be related to the relatively late activation of embryonic rRNA genes transcription and to the expressed rapidity of this process.