Radical solutions and cultural problems: could free oxygen radicals be responsible for the impaired development of preimplantation mammalian embryos in vitro?

A major obstacle to the study of mammalian development, and to the practical application of knowledge gained from it in the clinic during therapeutic in vitro fertilisation and embryo transfer (IVF-ET), is the propensity of embryos to become retarded or arrested during their culture in vitro. The precise developmental cell cycle in which embryos arrest or delay is characteristic for the species and coincides with the earliest period of embryonic gene expression. Much evidence reviewed here implicates free oxygen radicals (FORs) in the process of arrest. Thus, studies on the development of mouse preimplantation embryos in vitro have shown that (i) FORs are elevated in vitro, but not in vivo, at the time at which embryos become arrested or delayed, (ii) systems for removing reactive oxygen species to limit the formation of hydroxy radicals are present, although they have not yet been assessed quantitatively and may differ qualitatively from those in adult cells, (iii) metabolic and possibly genetic adaptations to oxidative damage are evident, (iv) published procedures for overcoming in vitro arrest are explicable in terms of FOR-mediated damage or responses and (v) the arrest or delay of most embryos in vitro can be reduced or prevented experimentally by addition of metal chelators to limit hydroxy radical formation and lipid hydroperoxidation.