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Membrane sterols and the development of the preimplantation mouse embryo
Abstract:
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 ther 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.
Insights
Oxygenated sterols disrupt mouse embryo development by inhibiting membrane sterol synthesis, crucial for cell adhesion and compaction. Restoring sterol levels reverses these effects, highlighting their importance for early embryonic growth.
Area of Science:
- Developmental Biology
- Cell Biology
- Reproductive Biology
Background:
- Membrane sterols, particularly cholesterol, are vital for cell membrane structure and function.
- Oxygenated sterols can interfere with cellular sterol metabolism and membrane composition.
- The specific role of sterols in early mammalian embryo development requires further elucidation.
Purpose of the Study:
- To investigate the impact of oxygenated sterols on the compaction and development of preimplantation mouse embryos.
- To determine the susceptibility of different embryonic stages to sterol-induced developmental defects.
- To explore the potential for reversing or preventing these effects using sterol synthesis precursors.
Main Methods:
- Mouse embryos were incubated with 7-ketocholesterol and other oxygenated sterols at various concentrations and durations.
- Embryo compaction, blastocyst formation, and ultrastructure were assessed.
- Developmental effects were evaluated in the presence of sterol synthesis precursors like mevalonate, desmosterol, and cholesterol.
Main Results:
- Oxygenated sterols inhibited embryo compaction and blastocyst formation in a dose- and time-dependent manner.
- Precompaction 8-cell embryos were most sensitive, failing to compact but continuing to divide.
- 7-ketocholesterol altered the ultrastructure of the smooth endoplasmic reticulum.
- Developmental and ultrastructural defects were reversible or preventable by adding cholesterol precursors.
Conclusions:
- Membrane sterol composition is critical for normal compaction and cytokinesis in preimplantation mouse embryos.
- Mammalian embryos can synthesize membrane sterols from the 8-cell stage onwards.
- Oxygenated sterols pose a significant threat to early embryonic development by disrupting essential sterol homeostasis.