Hammer Mary-Anne, Baltz Jay M
Ottawa Health Research Institute (Hormones, Growth and Development Program), Ontario.
Mol Reprod Dev. 2003 Oct;66(2):153-61. doi: 10.1002/mrd.10343.
Early preimplantation mouse embryos are susceptible to the detrimental effects of increased osmolarity and, paradoxically, their in vitro development is significantly compromised by osmolarities near that of oviductal fluid. In vitro development can be restored, however, by several compounds that are accumulated by 1-cell embryos to act as organic osmolytes, providing intracellular osmotic support and cell volume regulation. Taurine, a substrate of the beta-amino acid transporter that functions as an organic osmolyte transporter in other cells, had been proposed to function as an organic osmolyte in mouse embryos. Here, however, we found that taurine is neither able to provide protection for in vitro embryo development against increased osmolarity nor is it accumulated to higher intracellular levels as osmolarity is increased, indicating that it cannot function as an organic osmolyte in early preimplantation embryos. In contrast, beta-alanine, the other major substrate of the beta-amino acid transporter, both protects against increased osmolarity and is accumulated to somewhat higher levels as osmolarity is increased, indicating that it is able to function as an organic osmolyte in embryos. However, we also found that beta-alanine is displaced from embryos by glycine-the most effective organic osmolyte in embryos previously identified-and beta-alanine does not increase protection above that afforded by glycine at concentrations near those in vivo. Thus, the beta-amino acid transporter is likely present in early preimplantation embryos to supply beta-amino acids such as taurine for purposes other than to serve as organic osmolytes.
早期着床前的小鼠胚胎易受渗透压升高的有害影响，矛盾的是，其体外发育会因接近输卵管液渗透压的环境而受到显著损害。然而，几种化合物可恢复其体外发育，这些化合物可被单细胞胚胎积累，作为有机渗透剂，提供细胞内渗透压支持和细胞体积调节。牛磺酸是β-氨基酸转运体的底物，在其他细胞中作为有机渗透剂转运体发挥作用，曾被认为在小鼠胚胎中作为有机渗透剂发挥作用。然而，我们发现，牛磺酸既不能保护体外胚胎发育免受渗透压升高的影响，也不会随着渗透压升高而在细胞内积累到更高水平，这表明它在早期着床前胚胎中不能作为有机渗透剂发挥作用。相比之下，β-丙氨酸是β-氨基酸转运体的另一种主要底物，既能防止渗透压升高，又会随着渗透压升高而积累到稍高的水平，这表明它能够在胚胎中作为有机渗透剂发挥作用。然而，我们还发现，β-丙氨酸会被甘氨酸（先前在胚胎中鉴定出的最有效的有机渗透剂）从胚胎中取代，并且在接近体内浓度的情况下，β-丙氨酸并不能提供比甘氨酸更高的保护。因此，β-氨基酸转运体可能存在于早期着床前胚胎中，用于供应牛磺酸等β-氨基酸，其目的并非作为有机渗透剂。
