The chances of detecting contaminants can also be increased by evaluating multiple developmental parameters. In contrast, embryos from inbred or outbred strains are more sensitive to culture conditions, which may greatly improve the sensitivity of the MEA to detect contaminants in the culture environment. Although most MEAs use embryos from hybrid mice, these embryos are relatively insensitive and will develop well in a variety of media. Finally, it is possible to alter the sensitivity of the MEA by using embryos from different strains of mice. Embryos will develop better when they are cultured in reduced oxygen, in groups, and with protein, so the use of atmospheric oxygen, individual culture, or culture in low protein or protein-free media will increase the sensitivity of the MEA. Alternatively, the gas atmosphere, culture volume, embryo density, and concentration of protein during the MEA can be manipulated. As a result, several studies have demonstrated that MEAs using one-cell embryos are more sensitive than MEAs utilizing two-cell embryos. One-cell embryos have not developed all of the necessary mechanisms to maintain intracellular homeostasis and have not yet activated the embryonic genome, so they are very sensitive to the culture environment. By increasing the amount of cellular stress the embryo must cope with under control conditions, the additional stress of contaminants should have a more pronounced effect on development, allowing detection in the MEA. All of these manipulations effectively alter the amount of stress placed on the embryo during culture. There are multiple ways to alter the sensitivity of a MEA, including changing the developmental stage of the embryo at the initiation of culture, the conditions used for culture, or the strain of mouse. The key to preventing such products from entering the clinic is to improve the sensitivity of MEAs and ensure clinically relevant results. The more troubling scenario is the possibility that a product could support the development of murine embryos but still be unsuitable for clinical use. If a given product inhibits the development of murine embryos, there is little question whether that product should be used for clinical ART. However, we are not aware of any experimental data comparing the minimal inhibitory concentrations of various contaminants on murine and human embryos. The use of the murine embryo in quality control assays requires one to assume that the sensitivity of the murine embryo to various contaminants is similar to, or even greater than, that of human embryos. Īlthough the mouse embryo assay (MEA) is used to screen many products before use in human assisted reproductive technologies (ART), the clinical relevance of its results must be interpreted cautiously. As a result, all supplies that will come into contact with the embryo and/or the culture medium should be subjected to strict quality control (QC) testing, including the ability to support the growth of murine embryos. Even when the highest-quality reagents and plasticware are used, the introduction of some unknown substances (contaminants) into the culture environment is unavoidable. The effects of culture conditions on embryo viability are widely acknowledged, but controlling these conditions is not always straightforward.
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