Dawson K M, Baltz J M
Department of Physiology, University of Ottawa, Ontario, Canada.
Biol Reprod. 1997 Jun;56(6):1550-8. doi: 10.1095/biolreprod56.6.1550.
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 cells, accumulate nonperturbing organic osmolytes in their cytoplasm. In the presence of any of a number of organic compounds that were proven or probable substrates of either the Gly or the beta transport systems, mouse embryo development in vitro was protected from raised osmolarity. Zygotes developed past the "2-cell block," and with most Gly or beta substrates, to the blastocyst stage. The most effective osmoprotectants were glycine, glutamine, betaine, proline, beta-alanine, and hypotaurine; several others were partially effective. A model Gly substrate, glycine, was effective at a much lower concentration (EC50 = 50 microM) than was a model beta substrate, beta-alanine (EC50 = 1.3 mM). The protective effect of these two compounds was additive, indicating a common mode of action. The various effective compounds tested do not all share metabolic pathways or other such properties in common. Thus, it is likely that cleavage-stage mouse embryos utilize them, in large part, as organic osmolytes.
无论是添加氯化钠还是棉子糖导致渗透压升高，都会同样抑制小鼠胚胎发育，这表明高渗透压本身对胚胎有害。面对渗透压升高，大脑和肾脏中的细胞以及可能许多其他细胞会在其细胞质中积累无干扰作用的有机渗透物。在存在多种已被证实或可能是甘氨酸或β转运系统底物的有机化合物的情况下，体外培养的小鼠胚胎发育可免受渗透压升高的影响。合子发育越过“2细胞阻滞”阶段，并且在大多数甘氨酸或β底物存在的情况下，发育到囊胚阶段。最有效的渗透保护剂是甘氨酸、谷氨酰胺、甜菜碱、脯氨酸、β-丙氨酸和亚牛磺酸；其他几种也有部分效果。一种典型的甘氨酸底物甘氨酸，其有效浓度（EC50 = 50 microM）远低于典型的β底物β-丙氨酸（EC50 = 1.3 mM）。这两种化合物的保护作用是相加的，表明它们具有共同的作用模式。所测试的各种有效化合物并非都具有共同的代谢途径或其他此类特性。因此，很可能卵裂期小鼠胚胎在很大程度上是将它们用作有机渗透物。
