Development of Mouse Embryos after Immunoneutralization of Mitogenic Growth Factors Mimics that of Cloned Embryos
The extent to which mitogenic growth factors influence embryo development is not well characterized. We sought to determine the effect of epidermal growth factor (EGF) and transforming growth factor α (TGFα) on naturally fertilized (in vivo-derived) and in vitro-fertilized mouse embryos, compared with that on cloned (intracytoplasmic nuclear injection-derived) mouse embryos, in which EGF and TGFα expression is markedly reduced. Immunoneutralization of EGF, TGFα, and EGF receptor by using specific antibodies significantly reduced the blastocyst development rate (in vivo-derived: 66%, 63%, and 63%, respectively; in vitro-fertilized: 57%, 55%, and 56%, respectively), increased the number of apoptotic nuclei (in vivo-derived: 9%, 10%, and 9%, respectively; in vitro-fertilized: 13%, 13%, and 13%, respectively), decreased the total number of cells (in vivo-derived: 87%, 85%, and 86%, respectively; in vitro-fertilized: 86%, 85%, and 86%, respectively), and increased the inner cell mass:trophectoderm ratios (in vivo-derived: 1:2.70 ± 0.05, 1:2.73 ± 0.04, 1:2.71 ± 0.06, respectively; in vitro-fertilized: 1:2.94 ± 0.02, 1:2.96 ± 0.02, 1:2.95 ± 0.02, respectively). In most cases, combined treatment with neutralizing antibodies to both EGF and TGF accentuated changes in these parameters. Further, the effect of combined immunoneutralization on these parameters in fertilized embryos was no different from those in cloned embryos. Therefore, normal expression of mitogenic growth factors is crucial for successful development of mouse embryos before implantation. Inhibiting the action of mitogenic growth factors causes fertilized embryos to exhibit developmental characteristics similar to those of cloned embryos, which may partially explain the poor developmental potential of cloned mammalian embryos.
Document Type: Research Article
Publication date: June 1, 2006
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Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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