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通过可能作为有机渗透物的氨基酸转运体底物从高渗环境中挽救晚期压缩阶段的小鼠胚胎发育。

Rescue of postcompaction-stage mouse embryo development from hypertonicity by amino acid transporter substrates that may function as organic osmolytes.

机构信息

Loeb Research Centre, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

出版信息

Biol Reprod. 2010 Apr;82(4):769-77. doi: 10.1095/biolreprod.109.081646. Epub 2009 Dec 16.

DOI:10.1095/biolreprod.109.081646
PMID:20018907
Abstract

Early preimplantation embryos are sensitive to external osmolarity and use novel mechanisms to accumulate organic osmolytes and thus control their cell volumes and maintain viability. However, these mechanisms are restricted to the cleavage stages of development, and it was unknown whether postcompaction embryos use organic osmolytes. Mouse embryos developing from the 8-cell stage formed blastocoel cavities in vitro at osmolarities up to 360 mOsM. Above this range, several putative organic osmolytes (alanine, glutamine, glycine, and beta-alanine) rescued blastocyst development, but several effective osmoprotectants in cleavage-stage embryos (such as betaine and proline) did not. At physiological osmolarities, each of these compounds resulted in significantly larger blastocysts. This was not due to increased cell numbers, which were unaffected in blastocysts by osmolarity in the range where blastocyst size was rescued by potential organic osmolytes, although cell number was decreased at higher osmolarities and was rescued by each osmolyte. The effective osmolytes were accumulated intracellularly by embryos developing in vitro from the 8-cell stage to blastocysts. However, unlike conventional organic osmolytes in somatic cells or those in cleavage-stage embryos, their intracellular concentrations were not increased with increasing external osmolarity. With the exception of beta-alanine, which is taken up via the beta-amino acid transport system, the effective osmolytes were transported by the B(0,+) system, which becomes highly active in blastocysts. The intracellular accumulation of these osmolytes in postcompaction embryos thus appears to support optimal development and blastocyst expansion at physiological osmolarities and may contribute to the embryo's ability to withstand stress.

摘要

早期的胚胎对外部渗透压敏感,它们利用新颖的机制来积累有机渗透物,从而控制细胞体积并维持细胞活力。然而,这些机制仅限于胚胎的卵裂阶段,人们尚不清楚致密化后的胚胎是否使用有机渗透物。从 8 细胞阶段发育而来的小鼠胚胎在渗透压高达 360 mOsM 的情况下可在体外形成囊胚腔。在这个范围之上,几种推测的有机渗透物(丙氨酸、谷氨酰胺、甘氨酸和β-丙氨酸)可挽救囊胚的发育,但在卵裂期胚胎中几种有效的渗透保护剂(如甜菜碱和脯氨酸)却不能。在生理渗透压下,这些化合物中的每一种都导致囊胚明显增大。这不是由于细胞数量增加所致,因为在渗透压范围内,囊胚的大小可以通过潜在的有机渗透物来挽救,而囊胚的细胞数量不受影响,尽管在较高渗透压下细胞数量减少,但每种渗透物都可以挽救。在体外从 8 细胞阶段发育为囊胚的胚胎可在细胞内积累有效的渗透物。然而,与体细胞中的传统有机渗透物或卵裂期胚胎中的有机渗透物不同,其细胞内浓度不会随外部渗透压的增加而增加。除了β-丙氨酸(通过β-氨基酸转运系统摄取)之外,有效的渗透物是通过 B(0,+)系统转运的,该系统在囊胚中高度活跃。因此,致密化后胚胎中这些渗透物的细胞内积累似乎支持在生理渗透压下的最佳发育和囊胚扩张,并可能有助于胚胎耐受应激的能力。

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