Transient release of calcium from inositol 1,4,5-trisphosphate-specific stores regulates mouse preimplantation development.
Transient release of calcium from inositol 1,4,5-trisphosphate-specific stores regulates mouse preimplantation development.
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DOI：
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发表时间：
1996-08
期刊：
影响因子：
4.6
通讯作者：
J. Stachecki;D. Armant
中科院分区：
文献类型：
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作者：
J. Stachecki;D. Armant
1，4，5-三磷酸肌醇在多种细胞系统中通过调节细胞内钙离子的释放来调节细胞的生长和分化，参与卵母细胞的激活。最近的研究表明，哺乳动物着床前的发育也可能受到细胞内钙离子释放的调节。在乙醇或离子霉素作用下，桑椹胚细胞内钙离子水平短暂升高后，空化和细胞分裂的速度加快。BAPTA-AM是一种细胞内钙离子的螯合剂，暴露在BAPTA-AM中的胚胎表现出短暂的基础钙水平随剂量的降低，对离子载体诱导的钙信号的暂时抑制，以及随后的囊胚腔形成的延迟。0.5微米的BAPTA-AM对基础细胞内钙离子水平无明显影响，但可螯合乙醇暴露后释放的钙离子，从而减弱乙醇诱导的空化加速。BAPTA-AM还以剂量依赖的方式抑制细胞分裂至16-细胞期，这与抑制空化有关。硫柳汞和1，4，5-三磷酸肌醇可显著提高小鼠桑椹胚胞内钙离子浓度，为1，4，5-三磷酸肌醇敏感钙库的存在提供了证据。虽然咖啡因不能释放细胞内的钙离子，但兰诺定诱导了少量的双相钙释放，这表明兰诺定敏感的钙库可能也存在于小鼠胚胎中。用钙调蛋白抑制剂W-7处理桑椹胚囊胚腔形成呈剂量依赖性延迟。10微米W-7暴露4小时并未显著改变空化，但减弱了离子载体对胚泡形成的刺激。这一发现表明，通过钙信号转导产生的发育效应是由钙调蛋白介导的。我们的结果表明，小鼠桑椹胚中钙的释放主要是通过肌醇1，4，5-三磷酸受体进行的，细胞内钙水平的变化可以加速或延缓胚胎的生长和分化，在卵母细胞的调节和胚胎发育之间提供了一种机制联系。
Inositol 1,4,5-trisphosphate can regulate growth and differentiation by modulating the release of intracellular Ca2+ in a variety of cellular systems, and it is involved in oocyte activation. Recent studies suggest that mammalian preimplantation development may also be regulated by the release of Ca2+ from intracellular stores. The rate of cavitation and cell division was accelerated after a transient elevation of intracellular Ca2+ levels was induced in morulae by exposure to ethanol or ionomycin. Embryos exposed to BAPTA-AM, a chelator of intracellular Ca2+, exhibited a brief dose-dependent reduction in basal Ca2+ levels, a temporal inhibition of ionophore-induced Ca2+ signalling and a subsequent delay in blastocoel formation. BAPTA-AM at 0.5 microM did not significantly alter the basal intracellular calcium level, but chelated Ca2+ that was released after ethanol exposure and thereby attenuated the ethanol-induced acceleration of cavitation. BAPTA-AM also inhibited cell division to the 16-cell stage in a dose-dependent manner, which correlated with the inhibition of cavitation. Thimerosal and inositol 1,4,5-trisphosphate significantly elevated the intracellular Ca2+ concentration in mouse morula-stage embryos, providing evidence for the existence of inositol 1,4,5-trisphosphate-sensitive Ca2+ stores. Although caffeine failed to release intracellular Ca2+, ryanodine induced a small biphasic release of Ca2+, suggesting that ryanodine-sensitive Ca2+ stores may also exist in mouse embryos. Morulae exposed to the calmodulin inhibitor W-7 exhibited a dose-dependent delay in blastocoel formation. A 4 hour exposure to 10 microM W-7 did not significantly alter cavitation, but attenuated the ionophore-induced stimulation of blastocoel formation. This finding suggests that the developmental effects produced through Ca2+ signalling are mediated by calmodulin. Our results demonstrate that Ca2+ release in mouse morulae occurs predominantly through the inositol 1,4,5-trisphosphate receptor, and that alteration of intracellular Ca2+ levels can accelerate or delay embryonic growth and differentiation, providing a mechanistic link between the regulation of oocyte and embryonic development.