J. D. Biggers

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.

Whitten (1956) showed that 8-cell mouse embryos develop into blastocysts in a simple chemically defined medium containing glucose, and McLaren & Biggers (1958) demonstrated that blastocysts cultured in this way produce normal mice when transferred into uteri of foster mothers. Whitten (1957) also showed that late 2-cell mouse embryos developed into blastocysts if lactate was incorporated in the medium but earlier stages did not cleave under these conditions. Thus the observation that mouse zygotes develop into normal blastocysts in the lumen of oviducts in organ cultures (Biggers, Gwatkin & Brinster, 1962) suggested that special conditions for initial development are provided by the tube. Recently, Whittingham & Biggers (1967) demonstrated that 1-cell embryos cleave to the 2-cell stage in a simple medium containing lactate and

Considerable advances in media development for the culture of preimplantation mammalian embryos have been made since mouse embryos were first cultured and successfully transferred to foster mothers. The purpose of this review is to detail the history of the development of chemically defined media for the culture of preimplantation embryos. Two approaches have been used to determine the composition of chemically defined media: the 'back-to-nature' approach and 'let the embryo choose' or empirical optimization approach. Recent developments, including the supplementation of media with amino acids and the use of sequential media for the extended culture of preimplantation embryos, are critically assessed. Importantly, it is recognized that even the best media currently used are not optimal and inevitably cause imbalances and stress to the embryos. Consequently, preimplantation embryos must adapt to the culture environment in order to survive. The adaptations to stress that occur when embryos are placed in a chemically defined environment are reviewed. The implications of these various stresses on the patterns of gene expression in the early embryo and their potential long-term effects are also emphasized. The scientific and ethical issues raised by the commercialization of human embryo culture media are briefly addressed.