ORGANIC OSMOLYTES AND EMBRYOS - SUBSTRATES OF THE GLY AND BETA-TRANSPORT-SYSTEMS PROTECT MOUSE ZYGOTES AGAINST THE EFFECTS OF RAISED OSMOLARITY

Mouse embryo development is identically inhibited by raised osmolarity , whether produced by added NaCl or raffinose, demonstrating that high osmolarity is itself detrimental to embryos. In the face of increased osmolarity, cells in the brain and kidney, and likely many other cell s, accumulate nonperturbing organic osmolytes in their cytoplasm. In t he presence of any of a number of organic compounds that were proven o r probable substrates of either the Gly or the beta transport systems, mouse embryo development in vitro was protected from raised osmolarit y. Zygotes developed past the ''2-cell block,'' and with most Gly or b eta substrates, to the blastocyst stage. The most effective osmoprotec tants were glycine, glutamine, betaine, proline, beta-alanine, and hyp otaurine; several others were partially effective. A model Gly substra te, glycine, was effective at a much lower concentration (EC50 = 50 mu M) than was a model beta substrate, beta-alanine (EC50 = 1.3 mM). The protective effect of these two compounds was additive, indicating a c ommon mode of action. The various effective compounds tested do not al l share metabolic pathways or other such properties in common. Thus, i t is likely that cleavage-stage mouse embryos utilize them, in large p art, as organic osmolytes.