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Modulation of mouse preimplantation development by epidermal growth factor receptor antibodies, antisense RNA, and
1Department of Obstetrics and Gynecology, University of California, Davis 95616-8615.
Abstract:
Two-cell mouse preimplantation embryos were cultured for 48 h in four different reagents to modulate epidermal growth factor (EGF) receptor function. These were rabbit polyclonal and mouse monoclonal antibodies to EGF receptor, EGF receptor antisense RNA, and EGF receptor antisense deoxyoligonucleotides. Embryos were scored for two endpoints: onset of cavitation as a measure of trophectoderm differentiation and mean embryo cell number as a measure of cell proliferation. The consistent observations were that cavitation was significantly accelerated by antibodies and delayed by antisense RNA and antisense deoxyoligonucleotides. None of these reagents exerted a significant effect on mean embryo cell number, with one exception, the polyclonal antibody. Our interpretation of these observations is that the antibody binding facilitated cavitation by mimicking natural ligand-receptor binding and inducing the signal transduction cascade that is typical for the EGF receptor. In the case of antisense RNA or deoxyoligonucleotide, we propose that they delayed onset of cavitation by interfering with EGF receptor production. We hypothesize that during this period of development, EGF receptor is concerned predominantly with the regulation of differentiation more than with cell proliferation.
Insights
Antibodies to the epidermal growth factor (EGF) receptor accelerated embryo cavitation, while antisense RNA/oligonucleotides delayed it. EGF receptor primarily regulates differentiation, not proliferation, in early mouse embryos.
Area of Science:
- Developmental Biology
- Cell Signaling
Background:
- The epidermal growth factor (EGF) receptor plays a crucial role in mammalian development.
- Understanding its precise function during preimplantation embryonic development is essential.
Purpose of the Study:
- To investigate the role of the EGF receptor in early mouse embryo development.
- To determine the effects of modulating EGF receptor function on trophectoderm differentiation and cell proliferation.
Main Methods:
- Culture of two-cell mouse embryos for 48 hours with reagents targeting the EGF receptor.
- Reagents included polyclonal and monoclonal antibodies, antisense RNA, and antisense deoxyoligonucleotides.
- Assessed onset of cavitation (trophectoderm differentiation) and mean embryo cell number (cell proliferation).
Main Results:
- Embryo cavitation was significantly accelerated by EGF receptor antibodies.
- Cavitation was significantly delayed by EGF receptor antisense RNA and antisense deoxyoligonucleotides.
- Cell proliferation was largely unaffected, except for a slight increase with polyclonal antibodies.
Conclusions:
- EGF receptor antibodies appear to mimic ligand binding, promoting differentiation.
- Antisense strategies suggest interference with EGF receptor production, delaying differentiation.
- The EGF receptor is hypothesized to primarily regulate differentiation over proliferation in early mouse embryos.