Membrane sterols and the development of the preimplantation mouse embryo

The role of membrane sterols in the compaction and subsequent development of the preimplantation mouse embryo was studied by incubating embryos in 7-ketocholesterol and other oxygenated sterols. These sterols have been shown to inhibit sterol synthesis and deplete membranes of cholesterol in a variety of other cell types. Compaction and subsequent blastocyst formation were normal when embryos were incubated in physiological sterols but were inhibited by oxygenated sterols to a degree which depended upon the concentration of sterol, duration of incubation and developmental age of the embryos. Precompaction 8-cell embryos were most susceptible to the action of these sterols and failed to compact (as assessed by cell flattening and increased intercellular adhesion) but continued to divide, whilst later stage embryos developed normally. 7-ketocholesterol had a specific effect on the ultrastructure of the smooth endoplasmic reticulum of treated embryos. The developmental and ultrastructural effects induced by the oxygenated sterols could be reversed or prevented by the use of products of the blocked reaction (i.e. mevalonate, desmosterol or cholesterol). These results substantiate the evidence that preimplantation mammalian embryos are capable of synthesizing membrane sterols from the 8-cell stage onwards and emphasize the importance of the sterol composition of membranes for normal cytokinesis and compaction of the mouse embryo.